FDG-P Application Manual UM DOC1705991 3

GE Healthcare
Original User Instruction
FASTlabTM & FASTlabTM 2 synthesizers
FDG Phosphate
Application Manual
GE Healthcare FDG phosphate Application Manual
DOC1705991 FASTlab & FASTlab 2 – Version 3
Warranty and liability
GE Healthcare (GEHC) does not accept liability for injury to personnel or damage to equipment that
may result from misuse of this equipment, failure to observe the hazard notices contained in this
manual, or failure to observe federal, state and/or local regulations.
Whilst every effort has been made to ensure the technical accuracy of this manual, the information
contained herein is subject to change without notice. GEHC makes no warranty of any kind with
regard to this material.
GEHC shall not be liable for errors contained herein, or for incidental or consequential damages
arising from the use of the equipment described in this manual.
Internet updates: Common Documentation library
FASTlab manuals are available for viewing and downloading via internet.
Please check regularly the GE Common Documentation Library (CDL) website for updates:
- Go to
http://apps.gehealthcare.com/servlet/ClientServlet?REQ=Enter%2bDocumentation%2bLi
brary.
- Click the “Radiopharmacy” menu entry.
- Select “FASTlab” in the Radiopharmacy Product drop down list.
- Select “All” in the Manual Types drop down list.
- Click “Search” at the bottom of the screen.
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ПРЕДУПРЕЖДЕНИЕ Това упътване за работа е налично само на английски език.

(BG)  Ако доставчикът на услугата на клиента изиска друг език, задължение на клиента
е да осигури превод.
 Не използвайте оборудването, преди да сте се консултирали и разбрали
упътването за работа.
 Неспазването на това предупреждение може да доведе до нараняване на
доставчика на услугата, оператора или пациентa в резултат на токов удар,
механична или друга опасност.
警告本维修手册仅提供英文版本。
(ZH-CN)  如果客户的维修服务人员需要非英文版本，则客户需自行提供翻译服务。
 未详细阅读和完全理解本维修手册之前，不得进行维修。
 忽略本警告可能对维修服务人员、操作人员或患者造成电击、机械伤害或其他形
式的伤害。
警告本服務手冊僅提供英文版本。
(ZH-HK)  倘若客戶的服務供應商需要英文以外之服務手冊，客戶有責任提供翻譯服務。
 除非已參閱本服務手冊及明白其內容，否則切勿嘗試維修設備。
 不遵從本警告或會令服務供應商、網絡供應商或病人受到觸電、機械性或其他的
危險。
警告本維修手冊僅有英文版。
(ZH-TW)  若客戶的維修廠商需要英文版以外的語言，應由客戶自行提供翻譯服務。
 請勿試圖維修本設備，除非您已查閱並瞭解本維修手冊。
 若未留意本警告，可能導致維修廠商、操作員或病患因觸電、機械或其他危險而
受傷。
UPOZORENJE Ovaj servisni priručnik dostupan je na engleskom jeziku.

(HR)  Ako davatelj usluge klijenta treba neki drugi jezik, klijent je dužan osigurati prijevod.
 Ne pokušavajte servisirati opremu ako niste u potpunosti pročitali i razumjeli ovaj
servisni priručnik.
 Zanemarite li ovo upozorenje, može doći do ozljede davatelja usluge, operatera ili
pacijenta uslijed strujnog udara, mehaničkih ili drugih rizika.
VÝSTRAHA Tento provozní návod existuje pouze v anglickém jazyce.

(CS)  V případě, že externí služba zákazníkům potřebuje návod v jiném jazyce, je zajištění
překladu do odpovídajícího jazyka úkolem zákazníka.
 Nesnažte se o údržbu tohoto zařízení, aniž byste si přečetli tento provozní návod a
pochopili jeho obsah.
 V případě nedodržování této výstrahy může dojít k poranění pracovníka prodejního
servisu, obslužného personálu nebo pacientů vlivem elektrického proudu, respektive
vlivem mechanických či jiných rizik.
ADVARSEL Denne servicemanual findes kun på engelsk.

(DA)  Hvis en kundes tekniker har brug for et andet sprog end engelsk, er det kundens
ansvar at sørge for oversættelse.
 Forsøg ikke at servicere udstyret uden at læse og forstå denne servicemanual.
 Manglende overholdelse af denne advarsel kan medføre skade på grund af elektrisk
stød, mekanisk eller anden fare for teknikeren, operatøren eller patienten.
WAARSCHUWING Deze onderhoudshandleiding is enkel in het Engels verkrijgbaar.

(NL)  Als het onderhoudspersoneel een andere taal vereist, dan is de klant verantwoordelijk
voor de vertaling ervan.
 Probeer de apparatuur niet te onderhouden alvorens deze onderhoudshandleiding
werd geraadpleegd en begrepen is.
 Indien deze waarschuwing niet wordt opgevolgd, zou het onderhoudspersoneel, de
operator of een patiënt gewond kunnen raken als gevolg van een elektrische schok,
mechanische of andere gevaren.
3/40
WARNING This service manual is available in English only.

(EN)  If a customer's service provider requires a language other than english, it is the
customer's responsibility to provide translation services.
 Do not attempt to service the equipment unless this service manual has been
consulted and is understood.
 Failure to heed this warning may result in injury to the service provider, operator or
patient from electric shock, mechanical or other hazards.
HOIATUS See teenindusjuhend on saadaval ainult inglise keeles

(ET)  Kui klienditeeninduse osutaja nõuab juhendit inglise keelest erinevas keeles, vastutab
klient tõlketeenuse osutamise eest.
 Ärge üritage seadmeid teenindada enne eelnevalt käesoleva teenindusjuhendiga
tutvumist ja sellest aru saamist.
 Käesoleva hoiatuse eiramine võib põhjustada teenuseosutaja, operaatori või patsiendi
vigastamist elektrilöögi, mehaanilise või muu ohu tagajärjel.
VAROITUS Tämä huolto-ohje on saatavilla vain englanniksi.

(FI)  Jos asiakkaan huoltohenkilöstö vaatii muuta kuin englanninkielistä materiaalia,
tarvittavan käännöksen hankkiminen on asiakkaan vastuulla.
 Älä yritä korjata laitteistoa ennen kuin olet varmasti lukenut ja ymmärtänyt tämän
huolto-ohjeen.
 Mikäli tätä varoitusta ei noudateta, seurauksena voi olla huoltohenkilöstön, laitteiston
käyttäjän tai potilaan vahingoittuminen sähköiskun, mekaanisen vian tai muun
vaaratilanteen vuoksi.
ATTENTION Ce manuel d’installation et de maintenance est disponible uniquement en anglais.

(FR)  Si le technicien d'un client a besoin de ce manuel dans une langue autre que l'anglais,
il incombe au client de le faire traduire.
 Ne pas tenter d'intervenir sur les équipements tant que ce manuel d’installation et de
maintenance n'a pas été consulté et compris.
 Le non-respect de cet avertissement peut entraîner chez le technicien, l'opérateur ou
le patient des blessures dues à des dangers électriques, mécaniques ou autres.
WARNUNG Diese Serviceanleitung existiert nur in englischer Sprache.

(DE)  Falls ein fremder Kundendienst eine andere Sprache benötigt, ist es Aufgabe des
Kunden für eine entsprechende Übersetzung zu sorgen.
 Versuchen Sie nicht diese Anlage zu warten, ohne diese Serviceanleitung gelesen und
verstanden zu haben.
 Wird diese Warnung nicht beachtet, so kann es zu Verletzungen des
Kundendiensttechnikers, des Bedieners oder des Patienten durch Stromschläge,
mechanische oder sonstige Gefahren kommen.
ΠΡΟΕΙΔΟΠΟΙΗΣΗ Το παρόν εγχειρίδιο σέρβις διατίθεται μόνο στα αγγλικά.

(EL)  Εάν ο τεχνικός σέρβις ενός πελάτη απαιτεί το παρόν εγχειρίδιο σε γλώσσα εκτός των
αγγλικών, αποτελεί ευθύνη του πελάτη να παρέχει τις υπηρεσίες μετάφρασης.
 Μην επιχειρήσετε την εκτέλεση εργασιών σέρβις στον εξοπλισμό αν δεν έχετε
συμβουλευτεί και κατανοήσει το παρόν εγχειρίδιο σέρβις.
 Αν δεν προσέξετε την προειδοποίηση αυτή, ενδέχεται να προκληθεί τραυματισμός
στον τεχνικό σέρβις, στο χειριστή ή στον ασθενή από ηλεκτροπληξία, μηχανικούς ή
άλλους κινδύνους.
FIGYELMEZTETÉS Ezen karbantartási kézikönyv kizárólag angol nyelven érhető el.

(HU)  Ha a vevő szolgáltatója angoltól eltérő nyelvre tart igényt, akkor a vevő felelőssége a
fordítás elkészíttetése.
 Ne próbálja elkezdeni használni a berendezést, amíg a karbantartási kézikönyvben
leírtakat nem értelmezték.
 Ezen figyelmeztetés figyelmen kívül hagyása a szolgáltató, működtető vagy a beteg
áramütés, mechanikai vagy egyéb veszélyhelyzet miatti sérülését eredményezheti.
4/40
AÐVÖRUN Þessi þjónustuhandbók er aðeins fáanleg á ensku.

(IS)  Ef að þjónustuveitandi viðskiptamanns þarfnast annas tungumáls en ensku, er það
skylda viðskiptamanns að skaffa tungumálaþjónustu.
 Reynið ekki að afgreiða tækið nema að þessi þjónustuhandbók hefur verið skoðuð og
skilin.
 Brot á sinna þessari aðvörun getur leitt til meiðsla á þjónustuveitanda, stjórnanda eða
sjúklings frá raflosti, vélrænu eða öðrum áhættum.
AVVERTENZA Il presente manuale di manutenzione è disponibile soltanto in lingua inglese.

(IT)  Se un addetto alla manutenzione richiede il manuale in una lingua diversa, il cliente è
tenuto a provvedere direttamente alla traduzione.
 Procedere alla manutenzione dell'apparecchiatura solo dopo aver consultato il
presente manuale ed averne compreso il contenuto.
 Il mancato rispetto della presente avvertenza potrebbe causare lesioni all'addetto alla
manutenzione, all'operatore o ai pazienti provocate da scosse elettriche, urti meccanici
o altri rischi.
このサービスマニュアルには英語版しかありません。
(JA)  サービスを担当される業者が英語以外の言語を要求される場合、翻訳作業はその
業者の責任で行うものとさせていただきます。
 このサービスマニュアルを熟読し理解せずに、装置のサービスを行わないでくだ
さい。
 この警告に従わない場合、サービスを担当される方、操作員あるいは患者さん
が、感電や機械的又はその他の危険により負傷する可能性があります。
경고 본 서비스 매뉴얼은 영어로만 이용하실 수 있습니다.

(KO)  고객의 서비스 제공자가 영어 이외의 언어를 요구할 경우, 번역 서비스를
제공하는 것은 고객의 책임입니다.
 본 서비스 매뉴얼을 참조하여 숙지하지 않은 이상 해당 장비를 수리하려고
시도하지 마십시오.
 본 경고 사항에 유의하지 않으면 전기 쇼크, 기계적 위험, 또는 기타 위험으로
인해 서비스 제공자, 사용자 또는 환자에게 부상을 입힐 수 있습니다.
BRĪDINĀJUMS Šī apkopes rokasgrāmata ir pieejama tikai angļu valodā.

(LV)  Ja klienta apkopes sniedzējam nepieciešama informācija citā valodā, klienta
pienākums ir nodrošināt tulkojumu.
 Neveiciet aprīkojuma apkopi bez apkopes rokasgrāmatas izlasīšanas un saprašanas.
 Šī brīdinājuma neievērošanas rezultātā var rasties elektriskās strāvas trieciena,
mehānisku vai citu faktoru izraisītu traumu risks apkopes sniedzējam, operatoram vai
pacientam.
ĮSPĖJIMAS Šis eksploatavimo vadovas yra tik anglų kalba.

(LT)  Jei kliento paslaugų tiekėjas reikalauja vadovo kita kalba – ne anglų, suteikti vertimo
paslaugas privalo klientas.
 Nemėginkite atlikti įrangos techninės priežiūros, jei neperskaitėte ar nesupratote šio
eksploatavimo vadovo.
 Jei nepaisysite šio įspėjimo, galimi paslaugų tiekėjo, operatoriaus ar paciento
sužalojimai dėl elektros šoko, mechaninių ar kitų pavojų.
ADVARSEL Denne servicehåndboken finnes bare på engelsk.

(NO)  Hvis kundens serviceleverandør har bruk for et annet språk, er det kundens ansvar å
sørge for oversettelse.
 Ikke forsøk å reparere utstyret uten at denne servicehåndboken er lest og forstått.
 Manglende hensyn til denne advarselen kan føre til at serviceleverandøren, operatøren
eller pasienten skades på grunn av elektrisk støt, mekaniske eller andre farer.
5/40
OSTRZEŻENIE Niniejszy podręcznik serwisowy dostępny jest jedynie w języku angielskim.

(PL)  Jeśli serwisant klienta wymaga języka innego niż angielski, zapewnienie usługi
tłumaczenia jest obowiązkiem klienta.
 Nie próbować serwisować urządzenia bez zapoznania się z niniejszym podręcznikiem
serwisowym i zrozumienia go.
 Niezastosowanie się do tego ostrzeżenia może doprowadzić do obrażeń serwisanta,
operatora lub pacjenta w wyniku porażenia prądem elektrycznym, zagrożenia
mechanicznego bądź innego.
OSTRZEŻENIE Niniejszy podręcznik serwisowy dostępny jest jedynie w języku angielskim.

(PL)  Jeśli serwisant klienta wymaga języka innego niż angielski, zapewnienie usługi
tłumaczenia jest obowiązkiem klienta.
 Nie próbować serwisować urządzenia bez zapoznania się z niniejszym podręcznikiem
serwisowym i zrozumienia go.
 Niezastosowanie się do tego ostrzeżenia może doprowadzić do obrażeń serwisanta,
operatora lub pacjenta w wyniku porażenia prądem elektrycznym, zagrożenia
mechanicznego bądź innego.
AVISO Este manual de assistência técnica encontra-se disponível unicamente em inglês.

(PT-BR)  Se outro serviço de assistência técnica solicitar a tradução deste manual, caberá ao
cliente fornecer os serviços de tradução.
 Não tente reparar o equipamento sem ter consultado e compreendido este manual de
assistência técnica.
 A não observância deste aviso pode ocasionar ferimentos no técnico, operador ou
paciente decorrentes de choques elétricos, mecânicos ou outros.
ATENÇÃO Este manual de assistência técnica só se encontra disponível em inglês.

(PT-PT)  Se qualquer outro serviço de assistência técnica solicitar este manual noutro idioma, é
da responsabilidade do cliente fornecer os serviços de tradução.
 Não tente reparar o equipamento sem ter consultado e compreendido este manual de
assistência técnica.
 O não cumprimento deste aviso pode colocar em perigo a segurança do técnico, do
operador ou do paciente devido a choques eléctricos, mecânicos ou outros.
ATENŢIE Acest manual de service este disponibil doar în limba engleză.

(RO)  Dacă un furnizor de servicii pentru clienţi necesită o altă limbă decât cea engleză, este
de datoria clientului să furnizeze o traducere.
 Nu încercaţi să reparaţi echipamentul decât ulterior consultării şi înţelegerii acestui
manual de service.
 Ignorarea acestui avertisment ar putea duce la rănirea depanatorului, operatorului sau
pacientului în urma pericolelor de electrocutare, mecanice sau de altă natură.
ОСТОРОЖНО! Данное руководство по техническому обслуживанию представлено только на

(RU) английском языке.
 Если сервисному персоналу клиента необходимо руководство не на английском, а
на каком-то другом языке, клиенту следует самостоятельно обеспечить перевод.
 Перед техническим обслуживанием оборудования обязательно обратитесь к
данному руководству и поймите изложенные в нем сведения.
 Несоблюдение требований данного предупреждения может привести к тому, что
специалист по техобслуживанию, оператор или пациент получит удар
электрическим током, механическую травму или другое повреждение.
UPOZORENJE Ovo servisno uputstvo je dostupno samo na engleskom jeziku.

(SR)  Ako klijentov serviser zahteva neki drugi jezik, klijent je dužan da obezbedi prevodilačke
usluge.
 Ne pokušavajte da opravite uređaj ako niste pročitali i razumeli ovo servisno uputstvo.
 Zanemarivanje ovog upozorenja može dovesti do povređivanja servisera, rukovaoca ili
pacijenta usled strujnog udara ili mehaničkih i drugih opasnosti.
6/40
UPOZORNENIE Tento návod na obsluhu je k dispozícii len v angličtine.

(SK)  Ak zákazníkov poskytovateľ služieb vyžaduje iný jazyk ako angličtinu, poskytnutie
prekladateľských služieb je zodpovednosťou zákazníka.
 Nepokúšajte sa o obsluhu zariadenia, kým si neprečítate návod na obluhu a
neporozumiete mu.
 Zanedbanie tohto upozornenia môže spôsobiť zranenie poskytovateľa služieb,
obsluhujúcej osoby alebo pacienta elektrickým prúdom, mechanické alebo iné
ohrozenie.
ATENCION Este manual de servicio sólo existe en inglés.

(ES)  Si el encargado de mantenimiento de un cliente necesita un idioma que no sea el
inglés, el cliente deberá encargarse de la traducción del manual.
 No se deberá dar servicio técnico al equipo, sin haber consultado y comprendido este
manual de servicio.
 La no observancia del presente aviso puede dar lugar a que el proveedor de servicios,
el operador o el paciente sufran lesiones provocadas por causas eléctricas,
mecánicas o de otra naturaleza.
VARNING Den här servicehandboken finns bara tillgänglig på engelska. .

(SV)  Om en kunds servicetekniker har behov av ett annat språk än engelska, ansvarar
kunden för att tillhandahålla översättningstjänster.
 Försök inte utföra service på utrustningen om du inte har läst och förstår den här
servicehandboken.
 Om du inte tar hänsyn till den här varningen kan det resultera i skador på
serviceteknikern, operatören eller patienten till följd av elektriska stötar, mekaniska
faror eller andra faror.
OPOZORILO Ta servisni priročnik je na voljo samo v angleškem jeziku.

(SL)  Če ponudnik storitve stranke potrebuje priročnik v drugem jeziku, mora stranka
zagotoviti prevod.
 Ne poskušajte servisirati opreme, če tega priročnika niste v celoti prebrali in razumeli.
 Če tega opozorila ne upoštevate, se lahko zaradi električnega udara, mehanskih ali
drugih nevarnosti poškoduje ponudnik storitev, operater ali bolnik.
DİKKAT Bu servis kılavuzunun sadece ingilizcesi mevcuttur.

(TR)  Eğer müşteri teknisyeni bu kılavuzu ingilizce dışında bir başka lisandan talep ederse,
bunu tercüme ettirmek müşteriye düşer.
 Servis kılavuzunu okuyup anlamadan ekipmanlara müdahale etmeyiniz.
 Bu uyarıya uyulmaması, elektrik, mekanik veya diğer tehlikelerden dolayı teknisyen,
operatör veya hastanın yaralanmasına yol açabilir.
7/40
VERSION HISTORY
Version Date Reason for change
1 OCT 2015 Initial release of the document
Correction of the amount of NaOH used for the hydrolysis
2 SEP 2016
p.20
3 MAY 2017 Update of company address.
8/40
ACRONYMS & GLOSSARY

°C Celcius degree
FDG 2-[18F]fluoro-2-deoxy-D-glucose
FID Flame ionization detector
FTAG 2-[18F]-fluoro-1,3,4,6-tetra-O-acetyl-D-glucose
GC Gas Chromatophy
GE General Electric
GEHC General Electric Healthcare
HLB Hydrolphilic-Lipophilic-Balanced
MeCN Acetonitrile
MSDS Material Safety Data Sheet
mL Milliliter
mm Millimeter
mg Milligram
min Minute
µL Microliter
µg Microgram
µS/cm microsiemens/centimeter
N Normality
NaOH Sodium Hydroxide
18O (-water) Oxygen istope 18 (enriched water)
PLC Programmable Logical Controler
pH Potentiel hydrogene
ppm Part per million
QC Quality Control
QMA (cartridge) Quaternary methyl ammonium (cartridge)
S3 Syringe 3 (the right hand syringe of the cassette)
TLC Thin Layer Chromatography
9/40
Contents
VERSION HISTORY 8
ACRONYMS & GLOSSARY 9
CHAPTER 1 - INTRODUCTION 12
CHAPTER 2 - RADIOPHARMACEUTICAL REQUIREMENTS 13
CHAPTER 3 - FDG PHOSPHATE CASSETTE 14
3-1 THE FDG PHOSPHATE CASSETTE 14
3-2 REAGENTS 14
3-3 CARTRIDGES 15
CHAPTER 4 - DESCRIPTION ON THE CHEMICAL PROCESS 17
4-1 PREPARATION OF THE FLUORINATING AGENT 17
4-2 SYNTHESIZER AND CASSETTE TEST 17
4-3 PRELIMINARY STEPS 17
4-4 ENRICHED WATER RECOVERY AND ELUTION 18
4-5 18F AZEOTROPIC DRYING 18
4-6 LABELLING THE PRECURSOR 18
4-7 PRELIMINARY FTAG PURIFICATION 19
4-8 HYDROLYSIS ON SOLID SUPPORT 20
4-9 PH AND OSMOLALITY ADJUSTMENT 20
4-10 PURIFICATION AND TRANSFER 20
4-11 GENERAL INFORMATION ON THE PROCESS 21
CHAPTER 5 - CALIBRATION OF THE RADIOACTIVITY DETECTORS 22
CHAPTER 6 - SYNTHESIS REPORT 24
6-1 INTRODUCTION 24
6-2 GENERAL INFORMATION 26
6-2-1 Process report 27
6-2-2 Yield summary 27
6-2-3 Activity trending 28
6-2-4 Trending 28
6-2-5 Log 28
6-2-6 Operator comment 28
6-2-7 Operator signature 28
6-2-8 Responsible signature 29
CHAPTER 7 - FDG PHOSPHATE QUALITY CONTROL 30

CHAPTER 8 - FDG PHOSPHATE CASSETTE REMOVAL 32
8-1 FDG PHOSPHATE CASSETTE REMOVAL AFTER SYNTHESIS – FASTLAB SYNTHESIZER 32
8-2 FDG PHOSPHATE CASSETTE REMOVAL AFTER SYNTHESIS – FASTLAB 2 32
8-3 DISCARDING OF THE CASSETTE 32
CHAPTER 9 - TROUBLESHOOTING 33
9-1 INTRODUCTION AND PRELIMINARY WARNING 33
9-2 LOW YIELD 33
9-2-1 Insufficient activity trapping on the QMA cartridge 34
9-2-2 QMA elution problem 35
9-2-3 The activity was not trapped properly on the tC18 cartridge before the hydrolysis 35
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9-2-4 Hydrolysis issue 36

9-2-5 Radiochemistry problem (Labelling or drying) 36
9-3 FLUCTUATING YIELDS 37
9-4 LOW, OR FLUCTUATING, VOLUME OF FDG IN THE FINAL SOLUTION 37
9-5 THE QUALITY OF THE FINAL PRODUCT DOES NOT MEET THE PHARMACEUTICAL REQUIREMENTS 38
9-5-1 The pH of the product is too high 38
9-5-2 The pH of the product is too low 38
9-5-3 The FDG solution is not clear and colourless 38
9-5-4 There are unknown radioactive impurities in the FDG solution 39
9-5-5 The amount of residual free 18F ions is abnormally high 39
9-5-6 The amount of acetonitrile is too high 39
9-5-7 The amount of ethanol is too high 39
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CHAPTER 1 - INTRODUCTION
The FASTlab is a compact automated system that converts externally produced radio-isotopes
(from cyclotron) into radiochemicals ready for further processing and quality control. This is
achieved thanks to single-use consumables, called cassettes, which the FASTlab actuates following
step-by-step sequences. The radioactive tracers produced by the FASTlab are usable in Positron
Emission Tomography (PET).
Important note: Please note that the FDG phosphate cassette can be used with both FASTlab and
FASTlab systems. The synthesis method and performances are the same for both systems, and
only minor differences in the handling of the equipment must be considered for the production of
FDG phosphate depending on the system you own. For this reason, this manual will refer to the
synthesizer equipment as the “FASTlab synthesizer” but all the information found in this manual is
valid for both FASTlab and FASTlab 2 synthesizer. Should there be a difference in operation between
the two systems, it will be clearly indicated in the text.
In addition to the global documentation package “FASTlab – User Documentation” described here
below, each tracer cassette has its own manual called “Application manual”. The application
manuals describe the specific cassette items such as cassette configuration, set up, residual
activity, specific activity detectors calibration procedure, the general chemical process and a
tracer-specific trouble shooting.
This “FASTlab – FDG phosphate Application Manual” contains the necessary information about the
specific FDG phosphate cassette and can be used to assist the operator during FDG phosphate
synthesis and troubleshooting operation with the FASTlab supervision software version 3.1.0.0 or
higher. Another document (DOC0283337) is available on CDL for production of FDG phosphate on
a FASTlab 1 with an older software version.
Before operating the FASTlab, each operator must read the “FASTlab – User documentation”
package and be fully aware of its content.
The “FASTlab – User Documentation” package consist of four manuals:
- FASTlab – Operator Manual

It contains the necessary information to assist the operator for a routine production using
the FASTlab: a description of the equipment, a description of the control tools and displays
available to the user, the calibration procedure for the activity detectors, and all the
required operating instructions.
- FASTlab – Service Manual

It contains all the information related to servicing and maintenance of the FASTlab: a
description of the maintenance mode, troubleshooting information, maintenance checks
and frequencies, etc.
- FASTlab – Pre-Installation and Installation Manual

It contains information about the site requirements and all the instructions to support a
proper installation of the FASTlab.
- FASTlab – Health, Safety and Regulatory Manual

It contains the health, safety and regulatory information and instructions such as cautions,
warnings, potential dangers, safety labels, etc.
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CHAPTER 2 - RADIOPHARMACEUTICAL REQUIREMENTS

All personnel must read this chapter and be fully aware of its contents before operating the
FASTlab.
All personnel associated with the operation and maintenance of the FASTlab must be appropriately
qualified for radiopharmaceutical production and must be made familiar with the use of the
FASTlab.
Operating personnel must be informed of all applicable health and safety regulations.
The FASTlab is not shielded. It must be operated within a hot cell with sufficient shielding to be
compliant with local radioprotection regulations. The waste bottle must be shielded, even when
located in the hot cell. It is mandatory to close the door of the hot cell and to keep the door closed
during transfer of the radioactive species from the cyclotron to the FASTlab, and during the entire
synthesis.
After use, and although rinsed, the disposable cassette contains residues of radioactive material.
Do not remove the cassette before sufficient decay. The cassette contaminated with radioactive
material must be discarded in compliance with local radiopharmaceutical regulations. Note that
the cassette can also be contaminated with long half-life radioactive target impurities. Measure
the remaining radioactivity on the cassette in order to ensure proper storage until sufficient decay.
It is mandatory to use a radiation monitoring system inside the hot cell in order to assess the level
of radioactivity inside the enclosure before any potential opening. It should be noted that the
purpose of the embedded radioactivity detectors from the FASTlab is to follow the radiochemical
process only. Under no circumstances can they be used to assess the radioactivity level inside the
hot cell.
The use of Personal Protective Equipment (PPE) such as safety glasses, gloves and a lab coat is
mandatory when handling the contaminated cassette or when operating the FASTlab after a hot
synthesis. Nitrile gloves are highly recommended when handling contaminated material, instead
of latex which is more porous.
The operator should wear personal dosimeter at any time while handling or working with
radioactive products.
For more information regarding health and safety considerations while operating the FASTlab,
please refer to the “FASTlab – Health, Safety and Regulatory Manual” supplied as a part of the
global documentation package “FASTlab – User Documentation”.
Proper Quality Control must be conducted on each batch of tracer solution produced using the
FASTlab, according to the local radiopharmaceutical laws and regulations.
Any and all radiopharmaceutical production with the FASTlab is the sole responsibility of the
qualified radiopharmacist, and must be conform to all local laws and regulations.
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CHAPTER 3 - FDG PHOSPHATE CASSETTE

3-1 The FDG phosphate cassette
The FDG phosphate synthesis using the FASTlab synthesizer is carried out in a disposable fluid
pathway called the FDG phosphate cassette.
The FDG phosphate cassette must be replaced between each synthesis to ensure clean and
reproducible operation for every FDG phosphate production.
The disposable cassette is an original GEHC design. It includes a 25-valves stopcock manifold, a
reaction vessel, two 6 mL syringes, one 1 mL syringe, connections for incoming and outgoing fluids,
spikes for the connection with the reagent vials, a water bag spike for the connection with the
water bag, and various solid phase cartridges.
The FDG phosphate cassette package can only be purchased from GEHC and includes a hard
plastic sheet containing the cassette itself and a vent filter within a double sealed plastic bag. In
addition, the 100 mL water bottles and the certificates are included in the FDG phosphate cassette
package.
Important note: The cassette pack does not contain the outlet product filter. It is mandatory to
use a 0.2 µm sterile filter between the cassette outlet line and the FDG collection vial.
FIGURE 3-1: The FDG phosphate cassette
3-2 Reagents
Five reagent vials are used in the FDG phosphate cassette. The eluent, acetonitrile, mannose triflate
precursor, sodium hydroxide (NaOH) and phosphate buffer are placed into the reagent barrels on
the manifold. Water is also used but is not included in the cassette slots. The water bag is separated
from the cassette in the packaging.
Please find a brief description and safety hazards of the reagents in the TABLE I below:
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Eluent Mannose Sodium

Phosphoric acid
triflate Acetonitrile hydroxide
FIGURE 3-2: Position of the reagents on the FDG phosphate cassette.
TABLE 1: Description of the reagents used in the FDG phosphate cassette.

Reagent Container Colour code Amount Hazards
Eluent mixture
containing:
- Kryptofix ® 3 mL glass vial –
- Potassium capped – 11 mm Orange 850 µL
carbonate neck
- Acetonitrile Flammable – Corrosive - Toxic
- Water
3 mL glass vial –
Mannose triflate
capped – 11 mm Light green 2.0 mL
in MeCN
neck
Flammable
5 mL glass vial –
Acetonitrile capped – 13 mm Green 4.2 mL
neck
Flammable - Toxic
5 mL PP vial –
Sodium hydroxide capped – 13 mm Red 4.2 mL
neck
Corrosive
5 mL glass vial –
Phosphoric acid capped – 13 mm Silver 4.3 mL
neck
Corrosive - Toxic
Important note: For complete information regarding safety and hazards of the reagents above-
mentioned, please refer to the MSDS of the cassette found in the cassette packaging, and the
“FASTlab – Health, Safety and Regulatory Manual”
3-3 Cartridges
Four cartridges are used on the FDG phosphate cassette. One QMA (light blue ring) to trap the
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incoming activity, one tC18 cartridge (red ring), one Oasis® HLB and one Alumina A (light apple green
ring) cartridge.
QMA tC18 Environmental Alumina A HLB
FIGURE 3-3: Position of the cartridges on the FDG phosphate cassette.
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CHAPTER 4 - DESCRIPTION ON THE CHEMICAL PROCESS

The production of 2-[18F]fluoro-2-deoxy-D-glucose (FDG) using the FASTlab synthesizer is
performed using the method described below.
One production takes about 25 minutes between the entry of the activity in the synthesizer, and
the end of the delivery of the FDG to the collection vial. The resulting FDG solution is clear, colourless
and lightly acidic. It is ready for Quality Control.
Important note: The FDG phosphate tracer data package (version 1.4.0.0 or higher) comes by
default with several synthesis sequences installed. All of them produce FDG phosphate in the
same formulation and quality. The small differences between the sequences are adaptation to
specific set-up. It is recommended to approve only one sequence in the “synthesis sequence
management” menu (see the “Pre-installation and Installation manual”).
Name of the sequence Description

GE_FDG_GEMS115FL Normal FDG phosphate sequence
GE_FDG_GEMS115FL_pH NLT5 Specific sequence for Japan
Large Target volume sequence. To be used in case more
than 5 mL of enriched water must be transferred from
GE_FDG_LTV_GEMS115FL
the cyclotron (see the “selection of the synthesis” section
of the “Operator manual”)
Sequence adapted for site at very high altitude (3600
GE_FDG_GEMS115FL_HighAltitude_01
m above sea level).
4-1 Preparation of the fluorinating agent

The radionuclide is produced in the form of fluoride ions by bombardment of [18O]-water with
accelerated protons. The amount of [18F]-radioactivity recovered usually ranges between 600 and
20000 mCi (22 and 740 GBq).
WARNING – For bombardment within the cyclotron target, the use of [18O]-water enriched above
95% is recommended. Commercially available [18O]-water does not usually require further
purification. Following irradiation, the irradiated [18O]-water should be colourless and free of any
visible contamination, with conductivity below 10 µS/cm. GE Healthcare makes no guarantee
regarding the presence in the final product of radio contaminants from the target, because such
impurities are site related (contributing factors: cyclotron and target maintenance, quality of
enriched water and irradiation parameters).
WARNING – GE Healthcare makes no guarantee regarding the performance of the FDG phosphate
process if the cyclotron is not operated and maintained following supplier specifications.
4-2 Synthesizer and cassette test

Those two tests can be performed at the beginning of a synthesis to verify the integrity of both the
FASTlab synthesizer and the FDG phosphate cassette mounted on it. Please refer to the
corresponding sections of the “FASTlab – Operator Manual” for more information on these tests.
4-3 Preliminary steps

The preliminary steps of the production of FDG phosphate can be started during the irradiation.
These first steps are performed before transfer of the activity into the synthesizer. They consist in:
- Punching the reagent vials on the spikes
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- Priming the water bag spike

- Pressurizing the reagent vials
- Conditioning the tC18, HLB and Alumina cartridges
The operator is informed as soon as the synthesizer is ready to receive the irradiated water by
means of a message displayed on the screen.
Duration of this step: ± 3 minutes
4-4 Enriched water recovery and elution

After bombardment the irradiated [18O]-water is transferred into the FASTlab synthesizer. The
radioactive solution is passed through one of the anion exchange cartridge (QMA) on which the
[18F]-fluoride ions are trapped while the enriched water is recovered for recycling.
The [18F]-fluoride ions are then eluted from the cartridge into the reaction vessel using 0.6 mL of a
solution containing Kryptofix K222, potassium carbonate, acetonitrile and water (eluent mixture).
Note that Kryptofix is necessary in a following step to perform the nucleophilic substitution
reaction.
4-5 18F azeotropic drying
After the transfer of the eluent containing the [18F]-ions in the reaction vessel, the solvents are
evaporated until dryness. During the drying process, a small amount of acetonitrile (80 µL) is added
to the reaction vessel. The evaporation is carried out with heating under nitrogen flow and under
vacuum.
4-6 Labelling the precursor

The mannose triflate precursor is added to the dry residue in the reaction vessel. A nucleophilic
substitution reaction occurs at 125°C in a closed environment. During the substitution, the
trifluoromethane sulfonate group of the mannose triflate precursor is replaced by the [18F] ion and
result in FTAG (2-[18F]-fluoro-1,3,4,6-tetra-O-acetyl-D-glucose).
The labelling reaction is the most critical step of the FDG synthesis. Any trace of impurity in the
incoming activity, the mannose triflate precursor, the eluent mixture, the nitrogen, the QMA
cartridge or the manifold might lead to a drop of the labelling yield.
H OCOCH3 H OCOCH3
OSO2CF3 H
O Nucleophilic
Nucleophilicsubstitution
substitution O
H3COCO H3COCO
H3COCO OCOCH3 H3COCO OCOCH3
H H H 18
F
H H H H
Mannose
Mannose triflate precursor
triflate precursor 2-[18F]-fluo-1,3,4,6-tetra-O-acetyl D glucose
2-[18F] fluoro-1,3,4,6-tetra-O-acetyl-D- glucose
([18F]-FTAG)
([18F]-FTAg)
FIGURE 4-1: The nucleophilic substitution in the FDG synthesis process
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4-7 Preliminary FTAG purification

In order to ensure a trapping efficiency of the FTAG of more than 95%, the acetonitrile
concentration in water should be lower than 15%. The product in the reaction vessel must therefore
be diluted.
3 mL of water is added to the reaction mixture (A) in the reaction vessel. This diluted solution (B) is
further diluted in two portions. 2 ml of this solution (B) is diluted with 4.0 ml of water (C) and then
passed through the reverse phase cartridge (tC18) later used for the hydrolysis step. This operation
is done a second time with the remaining solution in the reaction vessel (D) (FIGURE 4-2). After those
operations, the FTAG is trapped on the tC18 environmental cartridge and the solvents, unreacted
18F ions and impurities are washed off into the external waste bottle.
Dilution in reactor Homogenised
1.6 ml ACN + 3 mL H2O
Solution A Solution B
Dilution in syringe Homogenised in syringe Trapping on tC18
2.3 mL solution B
+ 4.0 mL H2O
Solution B Solution C
Dilution in syringe Homogenised in syringe Trapping on tC18
2.3 mL solution B
+ 4.0 mL H2O
Solution B Solution D
FIGURE 4-2: Trapping of the FTAG in solution on the tC18 environmental cartridge
The reactor is rinsed twice with 3 mL of water. The rinsing solution is also withdrawn and passed
through the tC18 cartridge.
After trapping of the labelled precursor onto the cartridge, the intermediate FTAG product is pre-
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purified. The cartridge is rinsed twice with water.
4-8 Hydrolysis on solid support

The acetylated compound (FTAG) is converted into FDG by removing the 4 acetyl protecting groups.
This de-protection is carried out when the product is trapped on the tC18 environmental cartridge
through alkaline hydrolysis. The hydrolysis is performed at room temperature by means of 2 mL of
NaOH 2 N
.
H OCOCH3 H OH
H H
O Hydrolysis
Hydrolysis
O
H3COCO HO
H3COCO OCOCH3 HO OH
H 18
F H 18
F
H H H H
2-[18F]-fluo-1,3,4,6-tetra-O-acetyl D glucose 2-[18F]-fluo-2-deoxy-D-glucose

2-[18F] fluoro-1,3,4,6-tetra-O-acetyl-D- glucose 2-[18F] fluoro-2-deoxy-D- glucose
([18F]-FTAG)
([18F]-FTAg)
([18F]-FDG)
([18F]-FDG)
FIGURE 4-3: The alkaline hydrolysis in the FDG synthesis process
4-9 pH and osmolality adjustment

After hydrolysis, the alkaline FDG solution is collected with water and mixed up with the
neutralization solution (phosphate buffer). 1.5 mL of phosphoric acid are used to neutralize the FDG
basic solution.
Note that unlike the labelling intermediate, FDG is not retained on the tC18 environmental cartridge,
and can be eluted simply with water.
Duration of the step: ± 45 seconds.
4-10 Purification and transfer

The resulting neutralized FDG solution is purified by passing through an Oasis® HLB cartridge
retaining partially hydrolysed compounds and non-polar by-products, and by passing through an
Alumina A cartridge retaining the last traces of unreacted 18F ions.
A 0.22 µm vented filter must be added at the end of the collection line as a final particle filter for
the FDG solution.
Important note: Users who wish to perform subsequent sterilization procedures may need
permission from third-party patent holders.
The cassette, the cartridges and the filter are rinsed with water in order to recover the residual FDG
remaining in the lines and to drain this FDG into the final vial.
Duration of the step: ± 2 minutes.
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4-11 General information on the process
- Typical average FDG yield (corrected for decay) : 85+ ± 4%

- Typical residual radioactivity on cassette after rinsing procedure (corrected for decay) :
0.8% of the starting radioactivity.
- Typical final volume : 15 ± 2 mL
- Total duration of the process : < 25 minutes (from the 18F activity transfer from the
cyclotron to the tracer transfer)
- Total volume of gas produced during a synthesis (±15 litres), if a collection bag is used, a 15
Litre one is recommended.
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CHAPTER 5 - CALIBRATION OF THE RADIOACTIVITY DETECTORS

The FASTlab synthesizer is equipped with build-in radioactivity detectors. Four of those detectors
are used to estimate the production yield in the report at the end of the synthesis of a FDG
phosphate production.
Over time, the radioactivity detectors might be subjected to a slight drift. That is why calibration of
the detectors is strongly recommended to keep a good estimation of the productions yields.
Yearly calibration of the detectors is recommended if the radioactivity range remains the same. A
calibration procedure must also be performed every time a new version of the tracer package is
uploaded in the software, or if the radioactivity level used for the synthesis is different than usual.
WARNING - The purpose of the embedded radioactivity detectors from the FASTlab is to follow the
radiochemical process only. Under no circumstances can they be used to assess the radioactivity
level inside the hot cell.
The calibration procedure requires comparison of the radioactivity on most of the components of
the cassette with the activity measurement done by the radioactivity detectors during the
synthesis. In order to achieve this, a regular FDG phosphate synthesis must be performed but the
“cassette rinsing” checkbox must be unchecked (i.e. one should not perform the cassette rinsing)
in order to precisely measure the residual activity on the cassette.
After the FDG production the cassette must be removed from the FASTlab synthesizer after a
timeframe sufficient enough to minimize the dose received by the operator, but short enough so
that residual radioactivity can still be measured on the different parts of the cassette.
Please disassemble the following parts and put them in a plastic bag for radioactivity counting with
a dose calibrator:
- The reaction vessel

- The transfer tubing
- The QMA cartridge
- The hydrolysis cartridge
- The Alumina cartridge
- The purification cartridge
Please note that the following parts, not on the cassette, also have to be counted:
- The content of the waste bottle. To do so please carefully pour the liquid contained in the
waste bottle into a container that fits into the dose calibrator for the radioactivity
measurement.
- The enriched water recovery vial
- The collected FDG product
Altogether, nine elements have to be counted (radioactivity and reference time). These data will be
entered in the FASTlab software as described in the “Calibration procedure” section of the FASTlab
documentation”.
Important note: This calibration method uses a hot run performed without the rinsing to precisely
evaluate the calibration parameters of the FASTlab. It is however also possible to modify the
calibration parameters of the radioactivity detectors manually by changing directly their value. This
procedure is explained in the chapter of the “FASTlab – Operator Manual” dedicated to the radio
detector calibration.
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Important note: The “Calibration Procedure” states that it is possible to perform the calibration
procedure either for the entire tracer package, or just for a specific sequence in the tracer package.
In the supervision, when asked to select a synthesis report for calibration, Please always uncheck
the “Configure calibration for the sequence defined in the report only” box when calibrating
the FDG phosphate production. The following confirmation message should then be displayed on
the screen, indicating that the calibration will be performed for the whole tracer package. Please
refer to the “Calibration procedure” section of the FASTlab documentation for more information.
FIGURE 5-1: The pop-up window informs you that you are calibrating the entire package and not just one
sequence in the package
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CHAPTER 6 - SYNTHESIS REPORT

6-1 Introduction
During or after a synthesis, a report window is available through the top menu bar. Click on the
“Report” then “Synthesis” menu entry to access the complete report menu.
The synthesis report is saved in the database when the operator clicks “Save” at the end of a
production or finalizes a calibration. Always save at the end of a production before viewing or
printing its report so you can be sure it has been finalized.
A report number is automatically generated by the system. This number is displayed on the upper
right corner of the synthesis report.
Important note: The report number is generated automatically is only PC specific. This means that
if two PC run the supervision software, their generated reports will have the same numbers even if
the production were different. Always verify both the report number AND the computer identifier
(recorded in the report) to identify a production.
The following part will describe the different information found in the synthesis report. For general
information and customisation of the report, please refer to the “Report” chapter of the ‘FASTlab –
Operator Manual”.
The reports’ layout is slightly different depending on the FASTlab supervision version, but they all
comprise the same information. Please find below and example of synthesis report as generated
by the FASTlab supervision version 3.1.0.0 and higher.
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6-2 General information

The general information at the beginning of the first page of the report is described in the following
table.
TABLE 2: Explanation of the general information contained in the report.

Field name Content
Tracer The name of the tracer that has been synthesized
The batch number of the production can be filled during
Customer batch
the production by the operator. If so, it will appear in this
number
location
Date Date of the synthesis
The name of the operator who entered its credentials at
Operator
the beginning of the production
Cassette test Name of the cassette test sequence used and unique
sequence GUID number (GE identification number)
Name of the synthesis sequence used and unique GUID
Synthesis sequence
number (GE identification number)
Synthesizer ID ID of the synthesizer used for the synthesis
Supervision software version – PLC version of the
Software version
synthesizer
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Field name Content

Identification of the workflow number. The first number is
the amount of syntheses performed with the computer,
and the second number, the sequence number in the
Workflow ID
process (please note that FDG phosphate is a single
sequence process, hence the second number will always
be 1)
Calibration report Report number of the last calibration of the radiodetectors
number for this tracer
Cassette expiry date Date of cassette expiry
Transcription of the numbers under the code bar of the
Cassette reference
cassette
Displays the name of the computer which has been used
Computer name*
for the synthesis.
* This entry appears only if the option has been selected in the settings; see “FASTlab
– Pre-Installation manual”.
6-2-1 Process report

In the process part of the report, the status of the lab unit test, the cassette test, the synthesis and
the cassette rinsing are reported as
· Synthesizer test: (Successful, Bypassed or Failed)

· Cassette test: (Successful, Bypassed, Failed or Aborted)
· Synthesis: (Not started, In progress, Successful, Failed or Aborted)
· Cassette rinsing: (Enabled or bypassed)
All the details are reported in the log table on the third page of the report.
The use or non-use of the pause and manual modes are also reported in this process report.
6-2-2 Yield summary

The synthesis report uses the calibrated radioactivity detectors of the FASTlab to calculate the yield
of the production thanks to a unique formula. The different data used for this calculation are
recorded in this part of the report. Please find a short explanation of the different fields in the TABLE
3 below.
TABLE 3: Explanation of the information contained in the report.

Field name Content
Time at reagent Time (hh:mm:ss) when the reagents have been punched
connection on the synthesizer (reagents in contact with the cassette)
Time at start of Time (hh:mm:ss) when the radioactivity has been
synthesis transferred into the synthesizer (start of synthesis)
Time at end of Time (hh:mm:ss) when the FDG is in the S3 syringe waiting
synthesis for transfer outside the cassette (end of synthesis)
Duration of the synthesis (between the time at start and
Synthesis duration
end of synthesis)
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Field name Content

Volume of the target chosen at the beginning of the
Target volume
synthesis
18F radioactivity measured by the built-in radioactivity
Starting activity detector behind the QMA cartridge when the [18F]-has
been trapped on the cartridge
FDG radioactivity measured by the built-in radioactivity
Tracer activity at end detector behind the right hand syringe when the FDG is
of synthesis contained in the syringe before the purification and
transfer to the collection vial.
Tracer activity at end FDG radioactivity measured by external detector (not
of transfer needed for the FDG synthesis)
Final volume of tracer after transfer. This value depends
Volume of tracer on the sequence selected at the beginning of the
production
Concentration at end Calculation of the activity concentration in the final
of synthesis product
Estimated Yield at
Calculation of the synthesis yield at end of synthesis (EOS)
end of synthesis
Estimated Yield Calculation of the synthesis yield taking account of decay
decay corrected correction between start and end of the synthesis.
6-2-3 Activity trending

The graph in this section shows the radioactivity trending of the four detectors used for FDG
phosphate during the synthesis. There are 14 checkpoints during the synthesis during which the
measures are taken, and an additional one during the (optional) cassette rinsing.
Provided the radioactivity detectors are properly calibrated, this can be a great tool to follow the
progress of the synthesis and check the radioactivity has been handled as usual during the process.
6-2-4 Trending
The table present on the third page summarize the different activity and temperature of the
reaction vessel at the check points of the synthesis.
6-2-5 Log
The log tables reports the important events occurring during the synthesis. Those events may be
information like the end of the synthesis, warning, like the impossibility to read to bar code/RFID of
the cassette, or errors like a problem of leak tightness, or a manual abort of the synthesis by the
operator.
6-2-6 Operator comment

The comments that can be entered during the synthesis or just before saving the report will be
displayed in this section. Some additional space is also left in order to add any manual comment
after printing the report.
6-2-7 Operator signature

Field reserved for the handwritten signature of the operator.
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Important note: There is no possibility to digitally sign the production report via the FASTlab
supervision software. The report must be printed and completed with a handwritten signature.
6-2-8 Responsible signature

Field reserved for the handwritten signature of the production responsible.
Important note: There is no possibility to digitally sign the production report via the FASTlab
supervision software. The report must be printed and completed with a handwritten signature.
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CHAPTER 7 - FDG PHOSPHATE QUALITY CONTROL

Proper Quality Control (shortened as QC) must be performed on every batch of solution produced
using the FASTlab synthesizer, in accordance with the local laws and regulations.
Systematic sterilization of the product thanks to a 0.2 µm sterile filter must be performed on the
produced FDG.
GE Healthcare takes no responsibility for the conversion of the produced radiochemical into a
radiopharmaceutical suitable for human body injection. This is solely the responsibility of the
customer and the qualified radiopharmacist on site.
Important note: It is recommended to regularly check the hand contamination of the operator
during QC work, both for safety and accuracy reasons.
Important note: The use of Personal Protective Equipment (PPE) such as safety glasses, gloves and
a lab coat is mandatory when proceeding to the QC analysis of the produced tracer. Nitrile gloves
are highly recommended when handling contaminated material, instead of latex which is more
porous.
Please handle the activity behind an appropriate shielding as much as possible even during QC
testing.
The operator should wear personal dosimeter at any time while handling or working with
radioactive products.
Find below the typical FDG quality control method (fully described in the European Pharmacopeia
and in the US Pharmacopeia).
TABLE 4: Typical QC methods for FDG phosphate solution

Type of Quality Control Suggested analytical methods
Radio-TLC scanner
Radiochemical purity HPLC equipped with a strongly basic anion-exchange column,
an electrochemical detector and a radio-flow detector
Radionuclidic purity* Gamma-ray spectrum recorded using a suitable instrument
Residual solvents (ethanol
GC equipped with a FID detector
and acetonitrile)
Color spot test (Nucl. Med. Biol. Vol. 24, pp. 193-195, 1997)
Residual Kryptofix
TLC detection (Nucl. Med. Biol. Vol. 16, pp. 358-387, 1989)
pH meter
pH
pH indicator paper strips
Sterility test Proven methods
Pyrogen/Endotoxin test Proven methods
* This test is mandatory in the scope of the Quality Control
WARNING – The final product filter, not included in the cassette package, must always be tested
for integrity (commonly thanks to a bubble point test). It is recommended to validate your site-
specific process of aseptic filtration.
The typical FDG quality control values, and the acceptable range as described by the
Pharmacopeia, are shown in the table below (TABLE 5).
TABLE 5: European and American Pharmacopeia specification compared with typical values obtained with
30/40
the FASTlab synthesizer FDG phosphate production

Type of Quality Typical FASTlab FDG
Eur. Ph. USP
control bulk QC*
Radiochemical purity > 95% > 90% > 98%
Radionuclidic purity 105-115 min 105-115 min 105-115 min
Acetonitrile < 4.1 mg/V ** Acetonitrile < 0.04% Acetonitrile < 50 ppm
Residual solvents
Ethanol < 5000 ppm Ethanol < 5000 ppm Ethanol < 4000 ppm
Residual Kryptofix < 2.2 mg/V** < 50 ppm < 50 ppm
pH 4.5-8.5 4.5-7.5 5.5 ± 0.5
ClDG content < 0.5 mg/V** < 1 mg/V** 2 µg/mL
Sterility Sterile Sterile Sterile
< 175 UI/mL
Bacterial endotoxins < 175 UI/mL < 175 EU/mL
< 175 EU/mL
* The typical values is simply an indication of the values usually obtained with the FASTlab
synthesizer. The acceptance range for the production differs from those values and can be found
in the tracer product datasheet.
** V stands for the maximum recommended injection volume (in most of the cases, 10 mL)
31/40
CHAPTER 8 - FDG PHOSPHATE CASSETTE REMOVAL

After use, the disposable FDG phosphate cassette contains residues of radioactive material, even
after the cassette rinsing. The handling of the contaminated cassette after a synthesis differs
depending on the synthesizer on which the synthesis took place. Should you own a FASTlab or a
FASTlab 2, please refer to the respective section below.
8-1 FDG phosphate cassette removal after synthesis – FASTlab synthesizer

WARNING – Always measure the remaining activity before working next to the synthesizer after a
production. Appropriate personal protection equipment must be worn at all time.
To remove the cassette, simply unclamp it and unfasten its connection to the [18O]-water recovery
vial. Do not remove the FDG phosphate cassette before complete decay if it is not necessary. It is
recommended to leave the cassette on the synthesizer until the next run before removing it. In
case the cassette has to be removed before complete decay, measure the radiation level before
the removal of the FDG phosphate cassette and make sure that no unnecessary radiation exposure
to the operator results from these operations.
8-2 FDG phosphate cassette removal after synthesis – FASTlab 2

WARNING – It is strongly recommended to ALWAYS unmount the cassette by opening the drawer
of the FASTlab synthesizer before turning the equipment off.
Upon activation of the FASTlab, the actuators rotate several times to reach their home central
position, which can cause residual reagents to be sent back to the recovery 18O-water vial if the
cassette is still mounted on the synthesizer.
After the synthesis, simply press the “Open drawer” button in the maintenance mode to unmount
the cassette from the FASTlab and automatically disconnect the line to the recovery water bottle.
Do not open the hot cell or remove the cassette from the open drawer before complete decay if it
is not necessary. It is recommended to do so only before the next run.
production. Appropriate personal protection equipment must be worn at all time.
In the case the cassette has to be removed before complete decay, measure the radiation level
before the removal of the FDG phosphate cassette and make sure that no unnecessary radiation
exposure to the operator results from these operations.
8-3 Discarding of the cassette

The FDG phosphate cassette contaminated with radioactive material has to be discarded in
compliance with local radioprotection regulations. It is recommended to store it behind shielding
for at least 48 hours after synthesis.
Important note: The FDG phosphate cassette can also be contaminated with long half-life
radioactive target impurities especially on the QMA cartridge. It is highly recommended to remove
the cartridge from the manifold and to store it in a long-life decay lead container.
32/40
CHAPTER 9 - TROUBLESHOOTING
9-1 Introduction and preliminary warning
This chapter is dedicated to the chemistry and quality control related troubleshooting.
This chapter is complementary with the troubleshooting chapter of the “FASTlab - Service Manual”.
Altogether they are dedicated to cover the most common problems that could occur during
automated synthesis with the FASTlab synthesizer.
This chapter covers the cassette parts and chemistry related problems.
The troubleshooting chapter of the “FASTlab - Service Manual” covers the hardware and software
related problems.
production. Wait for sufficient decay before removing the cassette, and ensure that the activity has
been located and that the cassette can be handled with minimum exposure of the operator.
Appropriate personal protection equipment must be worn at all time.
WARNING – The system should be powered off before any maintenance or service intervention on
the FASTlab unless the intervention requires parts to be powered on (e.g. for troubleshooting
purposes).
9-2 Low yield

Be aware that the activity measurements done by the built-in detectors and the yield mentioned
in the production reports are meaningful only if the detectors are well calibrated for the level of
activity used.
The measurements done by the activity detectors should be considered only indicative since the
accuracy of such type of detectors is limited.
To determine the yield in the most precise manner, the starting activity as well as the activity in the
final solution should be measured accurately using a separate dose calibrator.
In case of a low yield, the best practice to identify the error is to identify where and under what
form the missing activity is. Please note that this operation should be only performed by an
adequately trained radiochemist or similar, as it involves potential manipulation of activity.
Please use the low yield fault finder, and then go to the corresponding section in this chapter:
- 9-2-1: Insufficient activity trapped on the QMA cartridge

- 9-2-2: QMA elution problem
- 9-2-3: Trapping issue
- 9-2-4: Hydrolysis issue
- 9-2-5: Radiochemistry problem
33/40
Low yield default finder
9-2-1 Insufficient activity trapping on the QMA cartridge
9-2-1-1 The activity was not trapped properly on the QMA cartridge and a large amount of activity
is in the 18O enriched water recovery vial
This scenario can be explained by:
1. A defective QMA cartridge assembled on the cassette. In this case, wait for sufficient decay
before opening the hot cell, then start a new synthesis with a new cassette.
2. A high level of impurities in the irradiated 18O water, either target impurities or residual
impurities remaining in the recycled water from a previous production.
Important note: For bombardment within the cyclotron target, the use of 18O-water enriched
above 95% is recommended. Commercially available 18O-water does not usually require further
purification.
Following irradiation, the irradiated 18O-water should be colourless and free if any visible
contamination, with conductivity below 10 µS/cm (recommended). The volume of irradiated 18O-
water sent to the FASTlab synthesizer should be within the range of 0.5 to 5 ml for regular synthesis
sequences.
GE Healthcare makes no guarantee regarding the presence in the final product of radio
contaminants from the target because such impurities are site related (main contributing factors
are the cyclotron and target maintenance, the quality of the enriched water and the irradiation
parameters).
Important note: GE Healthcare makes no guarantee regarding the performance of the FDG
process if the cyclotron is not operated and maintained following supplier specifications.
34/40
9-2-1-2 The activity was not trapped properly into the QMA cartridge and the amount of
recovered 18O water is much lower than the target volume sent to the FASTlab
This is the result of the impossibility for the activity delivered by the cyclotron to flow properly
through the QMA cartridge to the water recovery vial:
1. The inlet activity tubing might not be well connected to the plunger. In this case, wait for
sufficient decay before opening the hot cell and properly connect the tubing.
2. The inlet activity tubing might not be leak tight anymore, or has been damaged and kinked.
Please follow the replacement procedure described in the FASTlab – Service Manual for
maintenance of this part.
3. An incorrect volume has been selected at the start of the production, and a portion of the
activity has been sucked to the waste bottle via the activity plunger.
4. The “Activity Received” button has been clicked before the complete transfer of the 18F to
the FASTlab synthesizer.
5. The tube for water recovery located on the first valve on the left of the manifold might be
squeezed (for example between the front face of the module and the hard cassette cover.
In this case a part of the enriched water will not pass through the cartridge during the
trapping step, and will remain in the conical reservoir;
6. The QMA (light blue ring) cartridge is blocked because of impurities coming out of the target.
A dark residue might be noticed on the QMA cartridge after the synthesis and some liquid
may have been left in the conical reservoir, unreacted.
7. The QMA cartridge is defective and clogged/blocked. In this case, the amount of recovered
water can be abnormally low, or there will be some liquid in the reservoir above the
cartridge after the synthesis, consisting of target water mixed with eluent.
8. The activity plunger might not be leak tight anymore. Please check the activity plunger
integrity by following the instructions described in the FASTlab – Service Manual, and
change the rubber O-ring if appropriate.
9-2-2 QMA elution problem

Such event can happen if the eluent vial is not properly pierced, or if something prevents the eluent
withdrawal:
1. Verify that the correct level of eluent has been withdrawn from the vial at the end of the
production and that there is no leak in the elution system.
2. Verify that the spike properly pierced the eluent vial
3. Verify that the 1 mL syringe piston is hooked as intended in its driver
9-2-3 The activity was not trapped properly on the tC18 cartridge before the hydrolysis
After the labelling step, the newly synthesized FTAG is diluted with water and trapped on the tC18
cartridge. There are several reasons that could explain a bad trapping of the activity on this
cartridge, and to identify the origin of the problem, it is strongly recommended to analyse the
content of the waste bottle by Thin Layer Chromatography or by radio-HPLC, after waiting for
sufficient decay to do so safely.
35/40
9-2-3-1 There is a large amount of FTAG or FDG in the waste bottle

This means that the labelled compound failed to be trapped on the tC18 cartridge and can be
explained by different reasons;
1. There is no water bag, or the water bag is not connected properly to the cassette. This
would obviously also lead to a lower amount of solution in the final vial
2. The ethanol vial has not been pierced properly, or a part of the septum obstructs the spike,
preventing the good conditioning of the cartridge.
3. The tC18 cartridge is defective or not adequately filled.
4. The trapping occurred at a room temperature higher than 35 °C. It is always highly
recommended to use the system in normal usage conditions (between 5 and 30°C with a
less than 80% relative humidity
9-2-4 Hydrolysis issue

The main part of the labelled solution has been successfully trapped on the cartridge, but the
hydrolysis reaction was incomplete.
This may also lead to a higher amount of partially hydrolysed compounds in the FDG solution (other
than 18F—ion.
1. The spike did not pierce properly the crimp cap of the sodium hydroxide vial or a piece of
rubber from the stopper is blocking the spike. Verify that the correct level of sodium
hydroxide has been withdrawn from the vial at the end of the production and that there is
no leak in the hydrolysis system.
2. There is no water bag, or the water bag is not connected properly to the cassette. This
would obviously also lead to a lower amount of solution in the final vial.
3. This may be related to non-conformity of the cassette or reagent.
9-2-5 Radiochemistry problem (Labelling or drying)
9-2-5-1 The main part of the activity in the waste bottle is in 18F- form
This means that the mannose triflate precursor was not properly labelled and that the main
fraction of the activity is still in the 18F- form after labelling and is not retained on the tC18 cartridge.
Different reasons can explain a failed labelling step using the FASTlab synthesizer:
1. Impurities or moisture in the nitrogen.
2. Impurities or moisture in the different reagents in the cassette.
3. The transfer line between the cyclotron and the FASTlab has not been rinsed or replace
frequently, leading to high levels of impurity in the incoming activity. The transfer lines
should be rinsed and dried after every production, and should be replaced at least on a
yearly basis to ensure good quality of the activity provided to the FASTlab.
4. The spike did not pierce properly the cap of the mannose triflate precursor vial (orange
cap). Please verify the amount of residual mannose triflate in the vial after the production.
5. The cassette was handled with wet hands (water, isopropanol, ethanol) and its manifold
36/40
has been contaminated with it during mounting on the FASTlab synthesizer.
6. The amount or the quality of the reagents is not correct.
7. There is a substantial amount of impurities of impurities coming out of the target lines in
the irradiated water, inhibiting the labelling synthesis.
8. The reactorY inlet or outlet tube are (partially) squeezed or clogged between the cassette
E front face of the synthesizer.
cover and the
S
9. One of the connector on the reaction vessel is (partially) unscrewed.
N
O
10. An inert gasY other than nitrogen is used.
E
11. The bottomSof the reaction vessel is not in contact with the heater, leading to a poor heat
transfer and an incomplete reaction.
12. Verify the accuracy of the reactor heater according to the procedure described in the
“FASTlab – Service Manual”.
9-3 Fluctuating yields

Isopropanol is commonly used to sterilize the inside of the hot cell. Accidental contamination of the
cassette and/or reagents with it may lead to yield fluctuation between productions.
9-4 Low, or fluctuating, volume of FDG in the final solution

Several factors may contribute to this situation.
1. There is no water bag or the water bag is not connected properly to the cassette preventing
water withdrawal by the water bag spike.
2. The hydrophobic nitrogen inlet filter is connected to the outlet tubing instead of a 22 µm
filter (hydrophilic membrane), so the line is blocked. In such a case, one of the silicone tubing
may pop out of its barb fitting, leading to a potential activity leak onto the synthesizer.
3. A silicone tube is squeezed between the front panel of the FASTlab synthesizer and the
cassette cover, preventing fluid movement in the cassette. In such a case, one of the
silicone tubing may pop out of its barb fitting, leading to a potential activity leak onto the
synthesizer.
This should be detected during the cassette tests.
4. A silicone tube is partially damaged and is not leak tight anymore.

5. The tC18 environmental cartridge or the alumina N cartridge used for the final purification
is defective or blocked (this happen very rarely), causing abnormally high back pressure.
6. The buffer vial has not been properly pierced, and the phosphate buffer failed to be
withdrawn and transferred to the right hand syringe during the production. In such a case,
the vial is still filled with liquid at the end of the process, and the pH of the [18F]-FDG solution
is too high.
7. There is an extension line mounted on one of the outlets of the cassette (to a dispensing
37/40
unit for example), and the inner diameter of this extension line is too narrow, leading to high
backpressure and potential leaks.
unit for example) and the 0.22 µm filter is not mounted at the end of this extension line, but
between the cassette outlet line and the extension. The gas used to flush the FDG solution
through the line is removed by the filter, and FDG might then remain stuck in the extension
line and not been pushed into the vial/dispensing unit.
unit for example) and some FDG solution leaks away from the connections between the
line and the cassette and/or the 0.22 µm filter.
10. The waste bottle is full.
11. The cassette is not properly mounted on the FASTlab synthesizer.
12. The operator is waiting too long before transferring the FDG out of the cassette. In case of
a very high activity production, radiolysis may occur in the concentrated solution, lowering
the production yield.
13. The temperature inside the hot cell is too high (above 35°C), which can lead to a lower
trapping efficiency of the FTAG compound on the tC18 cartridge.
If it is not possible to regulate the temperature inside the hot cell, using a cold water bottle
will balance the ambient temperature effect (water bottle kept in the fridge prior the
synthesis).
9-5 The quality of the final product does not meet the pharmaceutical requirements
9-5-1 The pH of the product is too high

In that case, the [18F]-FDG solution may also be slightly yellow. Several factors can contribute to a
higher pH of the solution. Please verify the following points:
1. The amount of sodium hydroxide used for the hydrolysis is incorrect.

In this case, the amount of residual sodium hydroxide in the vial is lower than usual after
production.
2. The buffer solution was not transferred properly into the right hand syringe during the
production.
In this case, the amount of residual sodium hydroxide in the vial is higher than usual.
9-5-2 The pH of the product is too low

A low pH is often related to an incomplete hydrolysis due to missing sodium hydroxide. In this case,
the [18F]-FDG solution may contain some non- or partially hydrolysed [18F]-FTAG, and the yield of
the production may be affected.
Please verify the amount of residual sodium hydroxide in its vial after synthesis.
9-5-3 The FDG solution is not clear and colourless
9-5-3-1 The FDG solution is cloudy

White particles in suspension can be observed if no 0.22 µm filter has been used to filter the final
product, or if the filter is defective. Such a cloudy [18F]-FDG solution can be recovered by a second
38/40
filtration through a 0.22 µm filter, but complete quality control must then be conducted on the
filtered product.
9-5-3-2 The FDG solution is yellowish

This may result from an improper purification through the tC18 cartridge in the case where the
solution was not properly neutralized with sodium hydroxide, leading to a high pH.
9-5-4 There are unknown radioactive impurities in the FDG solution

Some impurities are commonly produced during a [18F]-FDG production on the FASTlab synthesizer,
including:
- Free 18F- ions – less than 2% in the final solution
- [18F]-FTAG – less than 0.5% in the final solution
- Partially hydrolysed [18F]-FTAG – less than 0.5% in the final solution
No [18F]-FDM is produced by epimerization of [18F]-FDG under alkaline conditions at room

temperature.
If abnormally high amounts of non- or partially hydrolysed [18F]-FTAG are detected in the FDG
solution, this may indicate that the hydrolysis did not quantitatively occur because of some missing
sodium hydroxide.
If other unknown radioactive compounds are detected in the solution, this may have resulted from
the analytical method used for the quality control, or from a contamination of the sample or the
test equipment. In cases where the radiochemical purity is measured by Thin Layer
Chromatography (TLC), the TLC strips should not by dried at an elevated temperature after spotting
the sample just before migration to avoid degradation of the [18F]-FDG that would be also detected.
9-5-5 The amount of residual free 18F ions is abnormally high

18F- ions which did not label the precursor are drained to the waste bottle during the pre-
purification steps before the hydrolysis. The last traces of 18F- ions should be retained on the
alumina N cartridges. Therefore, the amount of residual 18F- ions in the solution is generally below
2%. However, with increasing specific radioactivity concentrations of [18F]-FDG there are increasing
effects from auto radiolysis and free radical formation which may result in rising levels of free
fluoride ion over time in the [18F]-FDG solution.
9-5-6 The amount of acetonitrile is too high

There are two possibilities when the amount of acetonitrile in the final product is too high:
1. The water bag is not properly punched: there is not enough water for rinsing the tC18
cartridge after the trapping of the FATG. In this case, the yield and the final volume should
also be lower than expected.
2. The cassette used is too old. If the cassette is out of date, some leakages could appear from
the stopcocks, which can generate acetonitrile residue in the final product.
9-5-7 The amount of ethanol is too high

Ethanol is used to condition the tC18 Environmental cartridge. The cartridge is then rinsed with
water. A higher amount of ethanol in the final [18F]-FDG solution means often means that the
amount of water used for the rinsing is lower than usual and is then often linked with a lower final
volume as the water withdrawal may have been hindered for the whole production.
39/40
About GE Healthcare
GE Healthcare provides transformational
medical technologies and services that are
shaping a new age of patient care. Our broad
expertise in medical imaging and information
technologies, medical diagnostics, patient
monitoring systems, drug discovery,
biopharmaceutical manufacturing
technologies, performance improvement and
performance solutions services help our
customers to deliver better care to more
people around the world at a lower cost. In
addition, we partner with healthcare leaders,
striving to leverage the global policy change
necessary to implement a successful shift to
sustainable healthcare systems.
Our “healthymagination” vision for the future
invites the world to join us on our journey as we
continuously develop innovations focused on
reducing costs, increasing access and
improving quality and efficiency around the
world.
GE Healthcare
3000 North Grandview Blvd
Waukesha, WI 53188
U.S.A.
www.gehealthcare.com
GEMS PET Systems AB

Husbyborg
SE-75228 Uppsala,
Sweden

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GE Healthcare

Original User Instruction

FASTlabTM & FASTlabTM 2 synthesizers

Warranty and liability

Internet updates: Common Documentation library

ПРЕДУПРЕЖДЕНИЕ Това упътване за работа е налично само на английски език.

UPOZORENJE Ovaj servisni priručnik dostupan je na engleskom jeziku.

VÝSTRAHA Tento provozní návod existuje pouze v anglickém jazyce.

ADVARSEL Denne servicemanual findes kun på engelsk.

WAARSCHUWING Deze onderhoudshandleiding is enkel in het Engels verkrijgbaar.

WARNING This service manual is available in English only.

HOIATUS See teenindusjuhend on saadaval ainult inglise keeles

VAROITUS Tämä huolto-ohje on saatavilla vain englanniksi.

ATTENTION Ce manuel d’installation et de maintenance est disponible uniquement en anglais.

WARNUNG Diese Serviceanleitung existiert nur in englischer Sprache.

ΠΡΟΕΙΔΟΠΟΙΗΣΗ Το παρόν εγχειρίδιο σέρβις διατίθεται μόνο στα αγγλικά.

FIGYELMEZTETÉS Ezen karbantartási kézikönyv kizárólag angol nyelven érhető el.

AÐVÖRUN Þessi þjónustuhandbók er aðeins fáanleg á ensku.

AVVERTENZA Il presente manuale di manutenzione è disponibile soltanto in lingua inglese.

경고 본 서비스 매뉴얼은 영어로만 이용하실 수 있습니다.

BRĪDINĀJUMS Šī apkopes rokasgrāmata ir pieejama tikai angļu valodā.

ĮSPĖJIMAS Šis eksploatavimo vadovas yra tik anglų kalba.

ADVARSEL Denne servicehåndboken finnes bare på engelsk.

OSTRZEŻENIE Niniejszy podręcznik serwisowy dostępny jest jedynie w języku angielskim.

OSTRZEŻENIE Niniejszy podręcznik serwisowy dostępny jest jedynie w języku angielskim.

AVISO Este manual de assistência técnica encontra-se disponível unicamente em inglês.

ATENÇÃO Este manual de assistência técnica só se encontra disponível em inglês.

ATENŢIE Acest manual de service este disponibil doar în limba engleză.

ОСТОРОЖНО! Данное руководство по техническому обслуживанию представлено только на

UPOZORENJE Ovo servisno uputstvo je dostupno samo na engleskom jeziku.

UPOZORNENIE Tento návod na obsluhu je k dispozícii len v angličtine.

ATENCION Este manual de servicio sólo existe en inglés.

VARNING Den här servicehandboken finns bara tillgänglig på engelska. .

OPOZORILO Ta servisni priročnik je na voljo samo v angleškem jeziku.

DİKKAT Bu servis kılavuzunun sadece ingilizcesi mevcuttur.

ACRONYMS & GLOSSARY

CHAPTER 7 - FDG PHOSPHATE QUALITY CONTROL 30

9-2-4 Hydrolysis issue 36

The “FASTlab – User Documentation” package consist of four manuals:

- FASTlab – Operator Manual

- FASTlab – Service Manual

- FASTlab – Pre-Installation and Installation Manual

- FASTlab – Health, Safety and Regulatory Manual

CHAPTER 2 - RADIOPHARMACEUTICAL REQUIREMENTS

CHAPTER 3 - FDG PHOSPHATE CASSETTE

FIGURE 3-1: The FDG phosphate cassette

Eluent Mannose Sodium

FIGURE 3-2: Position of the reagents on the FDG phosphate cassette.

TABLE 1: Description of the reagents used in the FDG phosphate cassette.

QMA tC18 Environmental Alumina A HLB

FIGURE 3-3: Position of the cartridges on the FDG phosphate cassette.

CHAPTER 4 - DESCRIPTION ON THE CHEMICAL PROCESS

Name of the sequence Description

4-1 Preparation of the fluorinating agent

4-2 Synthesizer and cassette test

4-3 Preliminary steps

- Priming the water bag spike

Duration of this step: ± 3 minutes