INTRODUCTION: N-position radiolabeled amino acids, such as N-(2-[(18)F]fluoropropionyl)-L-methionine ([(18)F]FPMET) as a derivative of L-methionine (MET), can potentially serve as a PET tracer for tumor imaging. In the current study, radiosynthesis and biological evaluation of [(18)F]FPMET as a new PET tumor agent are performed. METHODS: [(18)F]FPMET was synthesized by reacting 4-nitrophenyl 2-[(18)F]fluoropropionate ([(18)F]NFP) with MET. In vitro competitive inhibition and protein incorporation experiments were performed with Hepa1-6 hepatoma cell lines. The biodistribution of [(18)F]FPMET was determined in S180 fibrosarcoma-bearing mice. PET/CT studies of [(18)F]FPMET were conducted in S180 fibrosarcoma-bearing mice, A549 lung adenocarcinoma-bearing nude mice, and PC-3 prostate cancer-bearing nude mice. RESULTS: [(18)F]FPMET was synthesized in 72%± 4% uncorrected radiochemical yield (n=10) from [(18)F]NFP. In vitro experiments showed that [(18)F]FPMET was primarily transported through Na(+)-dependent system A, system ASC, and system B(0,+), and was not incorporated into protein. Biodistribution and PET/CT imaging studies indicated that [(18)F]FPMET could delineate S180 fibrosarcoma, A549 lung adenocarcinoma, and PC-3 prostate cancer. CONCLUSION: An efficient synthesis of N-position [(18)F]labeled amino acids with a classic [(18)F]NFP prosthetic group is developed. The results support that [(18)F]FPMET seems to be a potential tracer for tumor imaging with PET.
INTRODUCTION: N-position radiolabeled amino acids, such as N-(2-[(18)F]fluoropropionyl)-L-methionine ([(18)F]FPMET) as a derivative of L-methionine (MET), can potentially serve as a PET tracer for tumor imaging. In the current study, radiosynthesis and biological evaluation of [(18)F]FPMET as a new PETtumor agent are performed. METHODS: [(18)F]FPMET was synthesized by reacting 4-nitrophenyl 2-[(18)F]fluoropropionate ([(18)F]NFP) with MET. In vitro competitive inhibition and protein incorporation experiments were performed with Hepa1-6 hepatoma cell lines. The biodistribution of [(18)F]FPMET was determined in S180 fibrosarcoma-bearing mice. PET/CT studies of [(18)F]FPMET were conducted in S180 fibrosarcoma-bearing mice, A549 lung adenocarcinoma-bearing nude mice, and PC-3 prostate cancer-bearing nude mice. RESULTS: [(18)F]FPMET was synthesized in 72%± 4% uncorrected radiochemical yield (n=10) from [(18)F]NFP. In vitro experiments showed that [(18)F]FPMET was primarily transported through Na(+)-dependent system A, system ASC, and system B(0,+), and was not incorporated into protein. Biodistribution and PET/CT imaging studies indicated that [(18)F]FPMET could delineate S180 fibrosarcoma, A549 lung adenocarcinoma, and PC-3 prostate cancer. CONCLUSION: An efficient synthesis of N-position [(18)F]labeled amino acids with a classic [(18)F]NFP prosthetic group is developed. The results support that [(18)F]FPMET seems to be a potential tracer for tumor imaging with PET.
Authors: Oliver Clauß; Linda Schäker-Hübner; Barbara Wenzel; Magali Toussaint; Winnie Deuther-Conrad; Daniel Gündel; Rodrigo Teodoro; Sladjana Dukić-Stefanović; Friedrich-Alexander Ludwig; Klaus Kopka; Peter Brust; Finn K Hansen; Matthias Scheunemann Journal: Pharmaceuticals (Basel) Date: 2022-03-08