Elsevier

Seminars in Oncology

Volume 38, Issue 1, February 2011, Pages 70-86
Seminars in Oncology

Molecular imaging in oncology
Positron Emission Tomography Imaging of Cancer Biology: Current Status and Future Prospects

https://doi.org/10.1053/j.seminoncol.2010.11.005Get rights and content

Positron emission tomography (PET) is one of the most rapidly growing areas of medical imaging, with many applications in the clinical management of patients with cancer. The principal goal of PET imaging is to visualize, characterize, and measure biological processes at the cellular, subcellular, and molecular levels in living subjects using noninvasive procedures. PET imaging takes advantage of the traditional diagnostic imaging techniques and introduces positron-emitting probes to determine the expression of indicative molecular targets at different stages of cancer progression. Although [18F]fluorodeoxyglucose ([18F]FDG)-PET has been widely utilized for staging and restaging of cancer, evaluation of response to treatment, differentiation of post-therapy alterations from residual or recurrent tumor, and assessment of prognosis, [18F]FDG is not a target-specific PET tracer. Over the last decade, numerous target-specific PET tracers have been developed and evaluated in preclinical and clinical studies. This review provides an overview of the current status and trends in the development of non-[18F]FDG PET probes in oncology and their application in the investigation of cancer biology.

Section snippets

PET Probes for Imaging Angiogenesis

Angiogenesis, the formation of new blood vessels from pre-existing vasculature, plays a vital role in tumor growth and metastatic spread.10 Tumor growth beyond a few millimeters in diameter requires an independent vasculature for the cellular supply of oxygen and nutrients and removal of waste products.11 Tumor angiogenesis is a complex, multi-step process that follows a characteristic sequence of events mediated and controlled by growth factors, cellular receptors, and adhesion molecules.12, 13

PET Probes for Imaging Hypoxia

The prevalence of hypoxic areas is a characteristic feature of locally malignant solid tumors. It has been found that up to 50% to 60% of locally advanced solid tumors may exhibit hypoxic and/or anoxic tissue areas that are heterogeneously distributed within the tumor mass. These hypoxic areas result from an imbalance between oxygen supply and consumption, which is caused by abnormal structure and function of the microvessels supplying the tumor, increased diffusion distances between the

PET Probes for Imaging Apoptosis

Apoptosis, or type I cell death, is the organized energy-dependent self disassembly of unneeded or senescent cells. When triggered by appropriate internal and/or external signals, these cells undergo preprogrammed cytoplasmic shrinkage, membrane blebbing, and budding off of intracellular contents carefully packaged into small membrane bound packets that are subsequently ingested by adjacent cells and phagocytes without provoking an inflammatory response.83 Initiation of apoptotic cell death

PET Probes for Imaging Tumor Cell Proliferation

The proliferative activity of cells is one of the hallmarks of malignant tumors, and the majority of anticancer drugs are designed to inhibit cell proliferation. PET imaging for proliferation will help to detect proliferative changes in tumors occurring during various therapeutic interventions. [11C]-thymidine was the first PET radiotracer successfully used to evaluate proliferative activity in various tumors.93 Thymidine is a native nucleoside, which is incorporated into deoxyribonucleic acid

PET Probes for Imaging Epidermal Growth Factor Receptors

Epidermal growth factor receptor (EGFR) is associated with a well-characterized proto-oncogene that has been shown to promote tumor progression in several solid cancers.108 EGFR is a member of the structurally related ErbB family of receptor tyrosine kinases.109 The EGF family includes four receptors: HER1 (ErbB1), HER2 (ErbB2), HER3 (ErbB3), and HER4 (ErbB4).110 Activation of EGFR contributes to several tumorigenic mechanisms, and in many tumors, overexpression of EGFR may act as a prognostic

PET Probes for Imaging Somatostatin Receptors

Somatostatin exists in two isoforms: a short peptide having 14 amino acids, and a second peptide with 28 amino acids, both of which bind with high affinity to five receptor subtypes.117 A majority of malignant tumors, such as neuroendocrine tumor (NET), small cell lung cancer, breast tumor, and malignant lymphoma, overexpress multiple somatostatin receptor subtypes, of which the somatostatin receptor 2 (sst2) subtype is predominantly expressed.118

Somatostatin has a short plasma half-life (∼2

Conclusion and Perspectives

PET imaging has rapidly gained importance in preclinical and clinical applications for cancer diagnosis and treatment. PET imaging can provide a whole-body readout in an intact system, which is much more relevant and reliable than in vitro/ex vivo studies; decrease the workload and accelerate the drug development process; provide more statistically accurate results through longitudinal studies that can be performed in the same subject; facilitate lesion detection in cancer patients and patient

Acknowledgment

The authors would like to acknowledge the intramural research program at the National Institute of Biomedical Imaging and Bioengineering for financial support.

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    Publication of this article was supported by the intramural research program at the National Institute of Biomedical Imaging and Bioengineering.

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