Conventional anatomical imaging with CT and MRI has limitations in the evaluation of prostate cancer. PET is a powerful imaging technique, which can be directed toward molecular targets as diverse as glucose metabolism, density of prostate-specific membrane antigen receptors, and skeletal osteoblastic activity. Although 2-deoxy-2-18F-FDG-PET is the mainstay of molecular imaging, FDG has limitations in typically indolent prostate cancer. Yet, there are many useful and emerging PET tracers beyond FDG, which provide added value. These include radiotracers interrogating prostate cancer via molecular mechanisms related to the biology of choline, acetate, amino acids, bombesin, and dihydrotestosterone, among others. Choline is used for cell membrane synthesis and its metabolism is upregulated in prostate cancer. 11C-choline and 18F-choline are in wide clinical use outside the United States, and they have proven most beneficial for detection of recurrent prostate cancer. 11C-acetate is an indirect biomarker of fatty acid synthesis, which is also upregulated in prostate cancer. Imaging of prostate cancer with 11C-acetate is overall similar to the choline radiotracers yet is not as widely used. Upregulation of amino acid transport in prostate cancer provides the biologic basis for amino acid-based radiotracers. Most recent progress has been made with the nonnatural alicyclic amino acid analogue radiotracer anti-1-amino-3-18F-fluorocyclobutane-1-carboxylic acid (FACBC or fluciclovine) also proven most useful for the detection of recurrent prostate cancer. Other emerging PET radiotracers for prostate cancer include the bombesin group directed to the gastrin-releasing peptide receptor, 16β-18F-fluoro-5α-dihydrotestosterone (FDHT) that binds to the androgen receptor, and those targeting the vasoactive intestinal polypeptide receptor 1 (VPAC-1) and urokinase plasminogen activator receptor (uPAR), which are also overexpressed in prostate cancer.
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