Physics of Nuclear Medicine

Dr. Sajid Mushtaq

Head Department of Chemistry,
PIEAS
Contact: 0330-645-7858

E-mail: sajidmushtaq@pieas.edu.pk

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Nuclear Imaging and Radiotherapy?
 What is Nuclear Medicine?
 Nuclear medicine is classically defined as the application of radionuclides to

medicine.
 Nuclear medicine takes advantage of the unique properties of radioactive

elements, which have significantly different physical properties compared

to stable elements but identical chemical behavior.
 More specifically, radionuclides decay at a characteristic rate (i.e. half-life)

via the emission of particles or electromagnetic radiation (e.g. alpha,

positrons, gamma rays, etc.).
 These emissions can be harnessed to facilitate the imaging or therapy of

disease. Radiolabeled molecules, termed “radiopharmaceuticals,” are an

essential element in the field of nuclear medicine
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Nuclear Imaging and Radiotherapy?
 Radiopharmaceutical Chemistry
 Radiopharmaceutical chemistry is the branch of chemistry focused on the

design, synthesis, characterization and application of radioactive

compounds, known as radiopharmaceuticals, for use in medical imaging and
therapy.
 These compounds are typically composed of a radioactive isotope bound to

a biologically active molecule, which directs the radioactivity to specific

tissues or organs.
 Radiopharmaceuticals are crucial in diagnostic techniques such as positron

emission tomography (PET) and single-photon emission computed

tomography (SPECT), as well as in therapeutic applications, including
targeted radiotherapy for cancer treatment.
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Nuclear Imagin and Radiotherapy?
 Radiopharmaceutical chemistry

Figure L-1-1: Radiopharmaceutical definition and working mechanism [1]

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[1] https://www.iaea.org/newscenter/news/what-areradiopharmaceuticals
Nuclear Imaging and Radiotherapy?
 Nuclear Imaging

 Nuclear imaging works because biomolecules in the body are not radioactive.
 Radiopharmaceuticals are easy to distinguish from native molecules, giving very
high contrast for imaging.
 This is different from other imaging methods like CT, where all tissues produce
signals, and contrast comes from the differences in signal intensity.

 In theory, every molecule of a diagnostic radiopharmaceutical can be detected

during its lifetime, making the technique very sensitive.
 However, in practice, several factors limit detection:

 The sensitivity of detection devices,

 The absorption of emissions by the body (attenuation),
 The need to limit radiation exposure to patients,
 Half-life.

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 Nuclear Imaging and Radiotherapy?
A B

Figure L-1-2: Full body scan. (A) CT scan, (B) SPECT scan [2]
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[2] Journal of Nuclear Medicine
Nuclear Imaging and Radiotherapy
 Radiotherapy

 Nuclear radiotherapy, also known as radionuclide therapy, uses special

drugs called radiopharmaceuticals to send radiation directly to a specific
part of the body for treatment.
 For example, diphosphonates—which are commonly labeled with the
gamma-emitting radionuclide 99mTc to enable the imaging of bone
mineralization can also be labeled with a beta particle-emitting radionuclide
such as 153Sm to deliver therapeutic radiation to sites of new bone
formation, most typically for the treatment of cancer growth.
 Nuclear radiotherapy offers some significant advantages over traditional
systemic therapy with nonradioactive drugs (e.g. chemotherapy) and
external beam radiotherapy. Unlike traditional chemotherapeutics,
radiopharmaceuticals can deliver potent therapeutic doses to the target.
 Radiopharmaceuticals are administered at low molecular doses and
therefore do not generate the nonspecific off-target biochemical effects
that can be seen at higher doses of chemotherapeutics.
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 Nuclear Imaging and Radiotherapy
 Radiotherapy

Figure L-1-3: Full body scan

using 99mTc labelled MDP [3]

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Nuclear Imaging and Radiotherapy
 Continue

 Compared to external beam radiotherapy, molecularly targeted

radiopharmaceuticals are typically able to deliver radiation to tissues more
selectively than spatially-targeted external beam radiotherapy.
 For example, nuclear radiotherapy of thyroid cancer with Na 131I can deliver
up to 10–15 Gy to thyroid cancer cells without disturbing most adjacent
neck tissues. In contrast, only 5–7 Gy can be deposited in the thyroid cancer
cells during external beam radiotherapy due to concerns surrounding the
toxicity to normal tissues.
 Nuclear radiotherapy has its limitations. It depends on how well the
treatment targets the specific disease, usually cancer or hormone-related
issues.
 Another challenge is that the treatment can harm organs that help absorb,
transport, or remove the radioactive drugs from the body.

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Nuclear Imaging and Radiotherapy
 Radiotherapy

Figure L-1-4: Setup of external beam therapy

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Nuclear Imaging and Radiotherapy
 Why choose nuclear medicine compared to other
alternatives.

 Nuclear imaging and radiotherapy gain their principal advantages over

competing approaches from the “tracer principle.”
 The essence of “tracer principle” is that radiopharmaceuticals are
administered at such low molar masses that they can create high-contrast
images or deliver therapeutic doses without disturbing native biochemistry
whatsoever.
 Nuclear medicine is most useful for processes that are very sensitive to
small amounts of external substances, like metabolism, how cells bind to
receptors, and how they move things in and out.
 This gives it an advantage over other imaging and therapy methods.

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Nuclear Imaging and Radiotherapy
 Why choose nuclear medicine compared to other
alternatives.
 However, nuclear medicine approaches certainly have some disadvantages
compared to other imaging and therapeutic modalities:
 Nuclear medicine offers limited spatial resolution compared to modalities
such as X-ray or CT.
 Nuclear medicine involves exposure to radiation, unlike modalities such as
MRI or ultrasound.
 Nuclear medicine requires patient-specific radiation safety precautions for
treatments, unlike chemotherapy and external beam radiotherapy.
 Ultimately, the advantages of nuclear approaches compensate their
disadvantages when applied to diseases associated with molecular targets
that can be targeted by diagnostic or therapeutic radiopharmaceuticals.
 This has directed to the considerable use of radiopharmaceuticals in both
clinical practice and clinical research.

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Nuclear Imaging and Radiotherapy
 Clinical Applications for Nuclear Imaging

 Nuclear imaging is a key tool for clinical diagnosis that is used thousands of
time each day around the world. It is most commonly used to detect and
quantify organ function and/or abnormal physiology and molecular
biochemistry in a variety of disorders.

 Below is a list of common clinical situations in which nuclear imaging is

applied, in rough order of frequency.

1. By imaging abnormal glucose metabolism using [18F]fluorodeoxyglucose

(FDG)
2. By imaging abnormal amino acid transport using [18F]fluciclovine
3. By imaging the expression of cancer-specific biomarkers using 18F- and 68Ga-
labeled small-molecule ligands that target prostate-specific membrane
antigen
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Nuclear Imaging and Radiotherapy
 Clinical Applications for Nuclear Imaging

Figure L-1-5: Chemical structure of [18F]fluciclovine and [18F]fluorodeoxyglucose

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Nuclear Imaging and Radiotherapy
 Clinical Applications for Nuclear Imaging

4. By imaging new bone formation associated with cancer growth using

[99mTc]methylene diphosphonate (MDP) or [18F]NaF.
5. By characterizing and quantifying the basis of hyper thyroidism indicated by
the uptake and retention of iodine using [123I]NaI
6. By localizing abnormal catecholamine-producing tumors such as
neuroblastomas using [123I]meta-iodobenzyl-guanidine (mIBG)
7. By localizing neuroendocrine tumors on the basis of somatostatin receptor
expression using [68Ga]-DOTATATE
8. By identifying significant coronary artery disease on the basis of the delivery
of perfusion agents retained in myocardium using [ 99mTc]sestamibi
9. By diagnosing Alzheimer’s dementia on the basis of the deposition of amyloid
in neural plaques using [11C] Pittsburgh compound B (PIB) or 18F-labeled
analogs
10. By determining the causes of renal dysfunction by tracing the clearance of
renal substrates using [99mTc] MAG3
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 Nuclear Imaging and Radiotherapy
 Clinical Applications for Nuclear Imaging

Figure L-1-6: Imaging amyloid deposition in Alzheimer’s dementia neural plaques

using [18F]AV-45. [18F] AV-45 PET images from an Alzheimer’s disease patient
(a) and a normal control subject (b)
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Nuclear Imaging and Radiotherapy
 Clinical Applications for Nuclear Imaging

11. By localizing bone trauma and infection on the basis new bone formation
using [99mTc]MDP
12. By localizing infection using white blood cells (WBCs) labeled using
[111In]oxime

 A shared goal in all these applications is to locate and measure specific

physical and molecular processes linked to abnormal organ function or
problems in tissues.

 In recent years, fundamental research in biology has managed to the

identification of new targets, and radiopharmaceutical chemists have used
this information for the creation of novel radiopharmaceuticals.

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Nuclear Imaging and Radiotherapy
 Clinical Applications for Nuclear Radiotherapy

 Nuclear radiotherapy, while certainly an important clinical tool, is somewhat

less commonly used than nuclear imaging. The first—and still most common—
use of nuclear radiotherapy is the treatment of hyperthyroidism.
 In this approach, modest doses of [131I]NaI provide a safe and highly effective
therapeutic alternative to more risky and/or toxic alternatives such as surgery
or antithyroid medications.
 Mostly nuclear therapy is used to treat cancer. While there is a small risk of
radiation affecting healthy tissues, this risk is offset by the potential for
effective treatment, especially in cases where other treatments haven't worked
well.
1. Painful bone metastases, using bone-targeting agents such as [89Sr]SrCl2,
[223Ra]RaCl2, and [153Sm]EDMP
2. Neuroblastoma using the catecholamine transporter substrate [131I]mIBG
3. Neuroendocrine tumors, using 177Lu or 90Y-labeled analogs of somatostatin
receptor-targeted peptides
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 Nuclear Imaging and Radiotherapy
 Clinical Applications for Nuclear Imaging

Figure L-1-7: Chemical structure of somatostatin peptide and Meta-

[131I]iodobenzylguanidine

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Nuclear Imaging and Radiotherapy
 Clinical Applications for Radioimmunotherapy

 An additional type of nuclear radiotherapy is termed

“radioimmunotherapy” and takes advantage of the specificity and affinity of
monoclonal antibodies for molecular markers of disease.
 Radioimmunotherapy is based on the use of therapeutic
radioimmunoconjugates, most commonly labeled with beta particle-
emitting radionuclides such as 131I or 90Y.
 The application of radioimmunotherapy to B-cell lymphoma generated
considerable excitement and resulted in two FDA-approved agents—Bexxar
and Zevalin—which are based on anti-CD20 antibodies labeled with 131I and
90
Y, respectively.
 Though these were popular at the time of their introduction, advances in
the application of non-labeled anti-CD20 antibodies (e.g. rituximab) and
other drugs limited the more widespread use of these agents.

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Nuclear Imaging and Radiotherapy
 Tricks of the Trade
 The current and future success of nuclear imaging and therapy depends on
several key technical issues:
Imaging instrumentation:
 Over 50 years nuclear medicine was brought into the mainstream by the
advent of the gamma camera, which enabled the practical collection of
high-quality single-photon emitting radiopharmaceutical images in the
clinic.
 In the 1990s and early 2000s, the advent of positron emission tomography
(PET) and PET/CT enabled clinical PET imaging to become an important and
rapidly advancing part of nuclear medicine.
 Advances in the design of detectors and imaging systems have played a
large role in the advancement of nuclear medicine and have enabled the
acquisition of high-quality, quantitative images with lower and lower doses
of radiopharmaceuticals.
 Further advances in the design of hybrid imaging platforms and novel
imaging devices will likely add significantly to our current capabilities
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Nuclear Imaging and Radiotherapy
 Tricks of the Trade
 The current and future success of nuclear imaging and therapy depends on
several key technical issues:

Image computing and analytics:

 Improvements in computer hardware and algorithms have made it possible

to get better image quality even with low tracer doses. This is achieved
through advanced methods of building and processing images.
 Further improvements in image analysis and advanced methods, like

machine learning for identifying important features, will help us get more
useful diagnostic information from nuclear imaging. This will also support
safer and more effective dose planning in nuclear radiotherapy

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Nuclear Imaging and Radiotherapy
 Tricks of the Trade

 Rapid progress in understanding the molecular biology of health and

disease is driving the shift toward specific medicine.

 Advances in nuclear medicine will focus on developing new and better

radiopharmaceuticals to support specific medicine.

 Paired diagnostic and therapeutic agents, called "theranostics," are

especially important.
 Theranostics help in selecting the right patients for treatment and

monitoring ongoing therapies.

 Radiopharmaceutical chemistry is expected to become more important in

nuclear medicine and biomedical research.

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Nuclear Imaging and Radiotherapy
 Will other Imaging and Therapeutic
Approaches Replace Nuclear Approaches?
 Using radioisotopes in nuclear medicine has some downsides, like practical

difficulties in radiolabeling and radiation exposure.

 This has led many to think that nuclear medicine might fade away,

especially with progress in other imaging technologies like CT and MRI.

 New non-nuclear probes with molecular capabilities, such as those used in

ultrasound, optical imaging, and MRI, have raised concerns about nuclear
medicine’s future.
 However, nuclear imaging procedures continue to retain significant

advantages over other approaches, especially when the application is

focused upon the molecular basis of the disease.
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Nuclear Imaging and Radiotherapy
 Will Other Imaging and Therapeutic
Approaches Replace Nuclear Approaches?

 The ongoing discovery of disease-specific biomarkers will provide an

increasing basis for the use of molecular tracers for the diagnosis and
treatment of disease .
 As a result, the ongoing application of nuclear medicine for diagnosis and

treatment will depend critically on radiochemistry.

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Nuclear Imaging and Radiotherapy
 Conclusion:
 Nuclear medicine is the application of radioactive elements to medicine.

 Radiopharmaceuticals operate on the “tracer principle,” namely, that radioactive

tracers are administered at such low molar doses that they do not perturb the
native biology of the system into which they are introduced.
 Nuclear imaging radiopharmaceuticals provide high sensitivity and molecular

specificity.
 Radionuclide therapy provides a highly targeted treatment modality based upon

the physical impact of radiation. It is similar to external beam radiotherapy but

much more targeted.
 The future of nuclear medicine relies on radiopharmaceutical chemists using new

discoveries in molecular biology to develop better methods for imaging and

treating diseases.
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References

1. Chiotellis Ε. Radiopharmaceutical Chemistry. Greek Ed. Pigasos, 2000

2. Saha G. Fundamentals of Nuclear Pharmacy. Springer, 7th Ed. 2018
3. Gregory R. Choppin Radiochemistry and Nuclear Chemistry 3 rd Edition 2001
4. Noboru Takigawa Fundamentals of Nuclear Physics Springer, 2016
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