New PET tracers for evaluation of solid tumor response to therapy.

ABSTRACT

We take advantage of the special characteristics of human tumors to image tumor response including predicting susceptibility to specific cancer therapies. The metabolic phenotype of malignancy, includes increased glycolysis (2-[(18)F]fluoro-2-D-deoxyglucose [FDG]), increased proliferation (2-[(18)F]fluoro-L-thymidine [FLT]), increased amino acid transport, as well as other functions such as fatty acid synthesis which have yet to be fully exploited. The endocrine dependent malignancies offer rich opportunities for selective imaging, including radioligands that have high affinity for hormone receptors, like androgen receptor (AR) (16Beta-[(18)F]16beta-[(18)F]fluoro-5alpha-dihydrotestoste-rone [FDHT]) and estrogen receptor (ER) ([(18)F]fluoroestradiol [FES]) and tissue specific transporters such as sodium iodide symporter (NIS) ((124)I). As knowledge of cancer biology has grown, it has become possible to develop tracers which image the client proteins involved in response to specific drugs, e.g. Gallium-68-Fab'2 herceptin for HER 2 effected by HSP 90 inhibitor drugs. More and more radiolabeled drugs will be used to explore the pharmacology of anticancer therapies, such as [(18)F]Desatinib. These may or may not be excellent imaging agents, but as analogs or even true tracers for specific anti-cancer drugs, noninvasive imaging through positron emission tomography will provide highly useful information, relating cancer pharmacology within the local tumor, to treatment response.