Synthesis and Biological Evaluation of O-[3-18F-fluoropropyl]-α-methyl Tyrosine in Mesothelioma-Bearing Rodents. (9th July 2013)

• Record Type: Journal Article
• Authors: Shih, I-Hong; Kong, Fan-Lin; Ali, Mohammad S.; Zhang, Yinhan; Yu, Dong-Fang; Duan, Xudong; Yang, David J.
• Other Names: Inoue Tomio Academic Editor.
• Is Part Of: BioMed research international. Volume 2013(2013)
• Publication Date: 2013-07-09
• Subjects: Medicine -- Periodicals; Biology -- Periodicals; Biotechnology -- Periodicals; Life sciences -- Periodicals; 610.5
• DOI: 10.1155/2013/460619
• Languages: English
• ISSNs: 2314-6133

Abstract

Abstract : 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.