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  • Review Article
  • Published:

Molecular imaging of cancer with positron emission tomography

Nature Reviews Cancer volume 2, pages 683–693 (2002)Cite this article

Key Points

  • Positron emission tomography (PET) is a method by which cellular and molecular events can be followed. Injected radiolabelled molecular probes (tracers) are used to map out the underlying biochemistry.

  • Both small-animal and clinical PET are being used to study cancer in living subjects.

  • 2-18F-fluoro-2-deoxy-D-glucose (FDG) is actively taken up and accumulates in cancer cells. It is useful for diagnosis, staging and monitoring the recurrence of various cancers, including lung, colorectal, melanoma, lymphoma, head and neck, as well as other malignancies.

  • Many tracers already exist for PET that measure cell proliferation, bone remodelling, perfusion, oxygen metabolism, tumour-receptor density and reporter-gene expression. A new generation of tracers is being developed that should help to form libraries of molecular probes for 'customized' imaging approaches.

  • Clinical PET/CT (computed tomography) scanners are now rapidly being installed, and form the basis for merging anatomical information (CT) with functional molecular information (PET) to further advance cancer management with FDG and, eventually, new-generation tracers.

  • Drug and tracer research and development are rapidly evolving and should help to accelerate both the pharmaceutical and imaging industries.

Abstract

The imaging of specific molecular targets that are associated with cancer should allow earlier diagnosis and better management of oncology patients. Positron emission tomography (PET) is a highly sensitive non-invasive technology that is ideally suited for pre-clinical and clinical imaging of cancer biology, in contrast to anatomical approaches. By using radiolabelled tracers, which are injected in non-pharmacological doses, three-dimensional images can be reconstructed by a computer to show the concentration and location(s) of the tracer of interest. PET should become increasingly important in cancer imaging in the next decade.

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Figure 1: Principles of positron emission tomography (PET).
Figure 2: FDG, FLT, fluoride ion and FHBG PET images.
Figure 3: FDG PET imaging for monitoring therapy.
Figure 4: Small-animal FDG/124I minibody imaging.
Figure 5: Bi-directional inducible therapeutic and reporter-gene expression.
Figure 6: MicroPET imaging of bi-directional inducible therapeutic and reporter-gene expression.
Figure 7: FDG PET/CT imaging for improved patient management.

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Acknowledgements

I thank M.E. Phelps, H.R. Herschman and J.R. Barrio for their strong mentorship over the last decade. I also thank N. Satyamurthy, M. Namavari, T. Toyokuni, J. Rao, A.Wu, L. Wu, H. Wu, M. Carey, A. Berk, O. Witte, C. Sawyers, R. Reiter, A. Beldegrun, J. Czernin, M. Seltzer, D. Silverman, C. Hoh, H.R. Schelbert, H. Kornblum, D. Smith, D. Agus, S.C. Huang, J. Braun, S. Chow, D.L. Kaufman, S.R. Cherry, A. Chatziioannou, M. Dahlbom and E. Hoffman for their enormous help over the years. Finally, I thank all the postdoctoral fellows, graduate and undergraduate students in my laboratory who have given and continue to enthusiastically give their full efforts towards building a new field of molecular imaging.

Author information

Authors and Affiliations

  1. Department of Molecular and Medical Pharmacology, Crump Institute for Molecular Imaging, UCLA School of Medicine, 700 Westwood Boulevard, Los Angeles, 90095-1770, California, USA

    Sanjiv Sam Gambhir

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DATABASES

Cancer.gov

bone cancer

brain cancer

breast cancer

colorectal cancer

lymphoma

melanoma

non-small-cell lung cancer

ovarian cancer

prostate cancer

GenBank

HSV1-tk

LocusLink

D2R

ERBB2

somatostatin receptor

Medscape DrugInfo

ganciclovir

penciclovir

tamoxifen

FURTHER INFORMATION

Academy of Molecular Imaging

FDG PET whole-body imaging atlas with over 100 oncology cases)

General resource for the molecular imaging field

Society for Molecular Imaging

Society of Nuclear Medicine

Glossary

TRACER

Also known as molecular probe or reporter probe. This molecule has a radioisotope attached to it and is injected in non-pharmacological amounts to provide imaging signal related to target(s) of interest. For PET tracers, the radioisotope is a positron emitter (e.g. 18F).

POSITRON

A particle that has the same mass as an electron, but that carries a positive charge.

CYCLOTRON

A device that is used to accelerate charged particles to create a collision between the charged particle and a target, so that a radioactive isotope can be produced for further incorporation into a molecule of interest.

GENERATOR

A device that is used to separate and extract a radioisotope through the use of a 'parent' isotope that constantly leads to a 'daughter' isotope.

PHARMACOKINETICS

The study of the time course of absorption, distribution, metabolism and excretion of drugs and their metabolites in body tissues and fluids.

SMART PROBES

Probes that are used in optical and magnetic resonance imaging that can be kept relatively silent until they interact with the target. After interaction, they become activated and produce a detectable signal.

MRI

(Magnetic resonance imaging). A technique to image subjects through the use of a magnetic field that aligns endogenous (for example, proton) or exogenous (for example, gadolinium) magnetic moments. Provides both anatomical imaging and functional imaging.

CHEMISORPTION

A chemical adsorption process in which weak chemical bonds are formed between gas or liquid molecules and a solid surface.

LIPOPHILICITY

The degree of affinity for fat.

MINIBODIES

An engineered antibody construct that consists of the variable-heavy- and variable-light-chain domains of a native antibody that is fused to the hinge region and to the CH3 domain of the immunogloblin molecule. Minibodies are small versions of whole antibodies, encoded in a single protein chain, that retain the antigen-binding region, the CH3 domain (to allow assembly into a bivalent molecule), and the antibody hinge (to accommodate dimerization by disulphide linkages).

DIABODIES

Engineered antibody fragments that are bivalent or bispecific molecules generated by dimerization of two variable-heavy–variable-light fragments. These molecules clear much more rapidly from the blood than do full antibodies.

Na/I SYMPORTER

A transporter that is found primarily in thyroid epithelial tissue that co-transports both iodide and sodium from extracellular fluid into cells.

SUICIDE GENE

A gene that can be introduced into target cells that will, under the appropriate conditions, lead to destruction of that cell. The herpes simplex virus type 1 thymidine kinase gene (HSV1-tk) is an example of a suicide gene. It encodes a protein that, in the presence of pro-drugs such as ganciclovir, leads to cell death. Suicide-gene-therapy approaches have been attempted as a way to destroy cancer cells.

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Gambhir, S. Molecular imaging of cancer with positron emission tomography. Nat Rev Cancer 2, 683–693 (2002). https://doi.org/10.1038/nrc882

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