Automated synthesis of 18F-fluoropropoxytryptophan for amino acid transporter system imaging.

OBJECTIVE: This study was to develop a cGMP grade of [(18)F]fluoropropoxytryptophan ((18)F-FTP) to assess tryptophan transporters using an automated synthesizer. METHODS: Tosylpropoxytryptophan (Ts-TP) was reacted with K(18)F/kryptofix complex. After column purification, solvent evaporation, and hydrolysis, the identity and purity of the product were validated by radio-TLC (1M-ammonium acetate : methanol = 4 : 1) and HPLC (C-18 column, methanol : water = 7 : 3) analyses. In vitro cellular uptake of (18)F-FTP and (18)F-FDG was performed in human prostate cancer cells. PET imaging studies were performed with (18)F-FTP and (18)F-FDG in prostate and small cell lung tumor-bearing mice (3.7 MBq/mouse, iv). RESULTS: Radio-TLC and HPLC analyses of (18)F-FTP showed that the Rf and Rt values were 0.9 and 9 min, respectively. Radiochemical purity was >99%. The radiochemical yield was 37.7% (EOS 90 min, decay corrected). Cellular uptake of (18)F-FTP and (18)F-FDG showed enhanced uptake as a function of incubation time. PET imaging studies showed that (18)F-FTP had less tumor uptake than (18)F-FDG in prostate cancer model. However, (18)F-FTP had more uptake than (18)F-FDG in small cell lung cancer model. CONCLUSION: (18)F-FTP could be synthesized with high radiochemical yield. Assessment of upregulated transporters activity by (18)F-FTP may provide potential applications in differential diagnosis and prediction of early treatment response.

Synthesis and biological evaluation of O-[3-18F-fluoropropyl]-α-methyl tyrosine in mesothelioma-bearing rodents.

Radiolabeled tyrosine analogs enter cancer cells via upregulated amino acid transporter system and have been shown to be superior to (18)F-fluoro-2-deoxy-D-glucose ((18)F-FDG) in differential diagnosis in cancers. In this study, we synthesized O-[3-(19)F-fluoropropyl]-α-methyl tyrosine ((19)F-FPAMT) and used manual and automated methods to synthesize O-[3-(18)F-fluoropropyl]-α-methyl tyrosine ((18)F-FPAMT) in three steps: nucleophilic substitution, deprotection of butoxycarbonyl, and deesterification. Manual and automated synthesis methods produced (18)F-FPAMT with a radiochemical purity >96%. The decay-corrected yield of (18)F-FPAMT by manual synthesis was 34% at end-of-synthesis (88 min). The decay-corrected yield of (18)F-FPAMT by automated synthesis was 15% at end-of-synthesis (110 min). (18)F-FDG and (18)F-FPAMT were used for in vitro and in vivo studies to evaluate the feasibility of (18)F-FPAMT for imaging rat mesothelioma (IL-45). In vitro studies comparing (18)F-FPAMT with (18)F-FDG revealed that (18)F-FDG had higher uptake than that of (18)F-FPAMT, and the uptake ratio of (18)F-FPAMT reached the plateau after being incubated for 60 min. Biodistribution studies revealed that the accumulation of (18)F-FPAMT in the heart, lungs, thyroid, spleen, and brain was significantly lower than that of (18)F-FDG. There was poor bone uptake in (18)F-FPAMT for up to 3 hrs suggesting its in vivo stability. The imaging studies showed good visualization of tumors with (18)F-FPAMT. Together, these results suggest that (18)F-FPAMT can be successfully synthesized and has great potential in mesothelioma imaging.