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.
Department of Experimental Diagnosis Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
I-Hong
IH
Shih
Fan-Lin
FL
Kong
Mohammad S
MS
Ali
Yinhan
Y
Zhang
Dong-Fang
DF
Yu
Xudong
X
Duan
David J
DJ
Yang
D000818:Animals; D003952:Diagnostic Imaging; D005462:Fluorine Radioisotopes / Q000008:administration & dosage / Q000737:chemistry*; D006801:Humans; D008654:Mesothelioma / Q000000981:diagnostic imaging*; D051379:Mice; D049268:Positron-Emission Tomography / Q000379:methods; D011859:Radiography; D019275:Radiopharmaceuticals; D051381:Rats; D014018:Tissue Distribution
D005462:Fluorine Radioisotopes; D019275:Radiopharmaceuticals