Fluoro-2-deoxy-d-glucose-positron emission tomography (FDG-PET) is utilized in more than 90% of cancers in staging, re-staging, assessing therapy response and during the follow-up. However, not all tumors show significant increase of metabolic activity on FDG-PET imaging. This is particularly true for prostate cancer, neuroendocrine tumors and hepatic tumors. In this review we have considered those already used for clinical applications such as 11C- and 18F-Choline, 11C-Methionine and 18F-FET, 18F-DOPA, 68Ga-DOTA-somatostatine analogues, 11C-Acetate and 18F-FLT. Choline presents a high affinity for malignant prostate tissue, even if low grade. Choline can be labeled with either 11C or 18F, the former being the preference due to lower urinary excretion and patients exposure. The latter is more useful for possible distribution to centers lacking in on-site cyclotron. Methionine is needed for protein synthesis and tumor cells require an external supply of methionine. These tracers have primarily been used for imaging of CNS neoplasms. The most appropriate indication is when conventional imaging procedures do not distinguish between edema, fibrosis or necrosis and disease relapse. In addition, the uptake of 11C-Methionine is proportional to the tumor grade and, therefore, the maximum small unilamellar vesicles (SUV) inside the brain mass before therapy is somehow considered a prognostic value. Neuroendocrine tumors (carcinoids, pheocromocytoma, neuroblastoma, medullary thyroid cancer, microcytoma, carotid glomus tumors, and melanoma) demonstrate an increased activity of L-DOPA decarboxylase, and hence they show a high uptake of 18FDOPA. For the study of NETs, 68Ga-DOTA-TOC/DOTA-NOC has been introduced as PET tracer. This compound for PET imaging has a high affinity for sst2 and sst5 and has been used in the detection of NETs in preliminary studies; 68Ga-DOTA-NOC PET is useful before metabolic radiotherapy in order to evaluate the biodistribution of the therapeutic compound; 18F-FLT is a specific marker of cell proliferation and the most important field of application of FLT is lung cancer. Other tracers are used in PET utilized as markers of hypoxia inside big neoplastic masses include 18F-MISO, 64Cu-ATSM, 18F-EF5, which highlight the presence of hypoxic areas are useful for patients that must be treated with radiotherapy.
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