Radiosynthesis and evaluation of N⁵-(2-¹⁸F-fluoropropanyl) ornithine as a potential agent for tumor PET imaging

Objective: Studies have confirmed that tumorigenesis is related to an imbalance of polyamine metabolism and over-expression of oncogenes resulting in the up-regulation of ornithine decarboxylase (ODC, the first ratelimiting enzyme for regulating intracellular polyamines biosynthesis), which has become a target for antitumor therapy. In this study, an ornithine derivative, N-5-(2-[F-18]fluoropropionyl) ornithine (N-5-[F-18]FPO), has been prepared and its potential utility for tumor PET imaging evaluated. Methods: N-5-[F-18]FPO was successfully prepared via a nucleophilic fluorination reaction and a subsequent efficient deprotection step. The in vitro and in vivo stability were determined by HPLC conducted in fetal bovine serum, saline and rat urine. Cellular uptake studies were conducted in HepG2 cells and the biodistribution and micro-PET/CT imaging performed in normal ICR mice and three tumor-bearing mice models, respectively. Results: Total synthesis time of N-5-[F-18]FPO was about 80 min with a radiochemical yield of 15% +/- 6% (uncorrected, based on F-18(-), n = 6) and a high radiochemical stability can be seen in vitro and vivo. The N-5-[F-18]FPO exhibited fast uptake in HepG2 cells and the cellular uptake ability of N-5-[F-18]FPO can be inhibited by L-ornithine and DFMO, which indicated that the transport pathway of N-5-[F-18]FPO is similar to that of Lornithine, interacting with ODC after being transported into the cell. The biodistribution and micro-PET/CT images demonstrate that N-5-[(FFPO)-F-18-F-] was excreted by the urinary system, and excellent tumor visualization with high tumor-to-background ratios can be observed in the three tumor-bearing mice models studied. Conclusion: All the above results suggest that N-5-[F-18]FPO has the potential to be a novel radiotracer for imaging ODC expression in solid tumors. (C) 2021 Elsevier Inc. All rights reserved.