Objective. This study was to develop a cGMP grade of [18F]fluoropropoxytryptophan (18F-FTP) to assess tryptophan transporters using an automated synthesizer. Methods. Tosylpropoxytryptophan (Ts-TP) was reacted with K18F/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 18F-FTP and 18F-FDG was performed in human prostate cancer cells. PET imaging studies were performed with 18F-FTP and 18F-FDG in prostate and small cell lung tumor-bearing mice (3.7 MBq/mouse, iv). Results. Radio-TLC and HPLC analyses of 18F-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 18F-FTP and 18F-FDG showed enhanced uptake as a function of incubation time. PET imaging studies showed that 18F-FTP had less tumor uptake than 18F-FDG in prostate cancer model. However, 18F-FTP had more uptake than 18F-FDG in small cell lung cancer model. Conclusion. 18F-FTP could be synthesized with high radiochemical yield. Assessment of upregulated transporters activity by 18F-FTP may provide potential applications in differential diagnosis and prediction of early treatment response.
Radiolabeled tyrosine analogs enter cancer cells via upregulated amino acid transporter system and have been shown to be superior to 18F-fluoro-2-deoxy-D-glucose (18F-FDG) in differential diagnosis in cancers. In this study, we synthesized O-[3-19F-fluoropropyl]-α-methyl tyrosine (19F-FPAMT) and used manual and automated methods to synthesize O-[3-18F-fluoropropyl]-α-methyl tyrosine (18F-FPAMT) in three steps: nucleophilic substitution, deprotection of butoxycarbonyl, and deesterification. Manual and automated synthesis methods produced 18F-FPAMT with a radiochemical purity >96%. The decay-corrected yield of 18F-FPAMT by manual synthesis was 34% at end-of-synthesis (88 min). The decay-corrected yield of 18F-FPAMT by automated synthesis was 15% at end-of-synthesis (110 min). 18F-FDG and 18F-FPAMT were used for in vitro and in vivo studies to evaluate the feasibility of 18F-FPAMT for imaging rat mesothelioma (IL-45). In vitro studies comparing 18F-FPAMT with 18F-FDG revealed that 18F-FDG had higher uptake than that of 18F-FPAMT, and the uptake ratio of 18F-FPAMT reached the plateau after being incubated for 60 min. Biodistribution studies revealed that the accumulation of 18F-FPAMT in the heart, lungs, thyroid, spleen, and brain was significantly lower than that of 18F-FDG. There was poor bone uptake in 18F-FPAMT for up to 3 hrs suggesting its in vivo stability. The imaging studies showed good visualization of tumors with 18F-FPAMT. Together, these results suggest that 18F-FPAMT can be successfully synthesized and has great potential in mesothelioma imaging.
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