Radiosynthesis and biological evaluation of N-(2-[18F]fluoropropionyl)-3,4-dihydroxy-l-phenylalanine as a PET tracer for oncologic imaging.

Abstract:

INTRODUCTION:Several 11C and 18F labeled 3,4-dihydroxy-l-phenylalanine (l-DOPA) analogues have been used for neurologic and oncologic diseases, especially for brain tumors and neuroendocrine tumors PET imaging. However, 18F-labeled N-substituted l-DOPA analogues have not been reported so far. In the current study, radiosynthesis and biological evaluation of a new 18F-labeled l-DOPA analogue, N-(2-[18F]fluoropropionyl)-3,4-dihydroxy-l-phenylalanine ([18F]FPDOPA) for tumor PET imaging are performed. METHODS:The synthesis of [18F]FPDOPA was via a two-step reaction sequence from 4-nitrophenyl-2-[18F]fluoropropionate ([18F]NFP). The biodistribution of [18F]FPDOPA was determined in normal Kunming mice. In vitro competitive inhibition and protein incorporation experiments were performed with SPC-A-1 lung adenocarcinoma cell lines. PET/CT studies of [18F]FPDOPA were conducted in C6 rat glioma and SPC-A-1 human lung adenocarcinoma and H460 human large cell lung cancer-bearing nude mice. RESULTS:[18F]FPDOPA was prepared with a decay-corrected radiochemical yield of 28±5% and a specific activity of 50±15GBq/μmol (n=10) within 125min. In vitro cell experiments showed that [18F]FPDOPA uptake in SPC-A-1 cells was primarily transported through Na+-independent system L, with Na+-dependent system B0,+ and system ASC partly involved in it. Biodistribution data in mice showed that renal-bladder route was the main excretory system of [18F]FPDOPA. PET imaging demonstrated intense accumulation of [18F]FPDOPA in several tumor xenografts, with (8.50±0.40)%ID/g in C6 glioma, (6.30±0.12)%ID/g in SPC-A-1 lung adenocarcinoma, and (6.50±0.10)%ID/g in H460 large cell lung cancer, respectively. CONCLUSION:A novel N-substituted 18F-labeled L-DOPA analogue [18F]FPDOPA is synthesized and evaluated in vitro and in vivo. The results support that [18F]FPDOPA seems to be a potential PET tracer for tumor imaging, especially be a better potential PET tracer than [18F]fluoro-2-deoxy-d-glucose ([18F]FDG) for brain tumor imaging.

journal_name

Nucl Med Biol

authors

Tang C,Nie D,Tang G,Gao S,Liu S,Wen F,Tang X

doi

10.1016/j.nucmedbio.2017.04.002

subject

Has Abstract

pub_date

2017-07-01 00:00:00

pages

39-46

eissn

0969-8051

issn

1872-9614

pii

S0969-8051(17)30040-9

journal_volume

50

pub_type

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