Synthesis and Evaluation of a 18F-radiolabeled ornithine as a potential tumor PET tracer

1117 Objectives: Polyamines are essential substances to maintain vital movement activities such as cell growth and differentiation. The activity of polyamine synthase is up-regulated due to the rapid proliferation of tumor cells requires high levels of polyamines. Ornithine is the main material for the synthesise of polyamines by the decarboxylation of ornithine decarboxylase (ODC). ODC is the frist rate-limiting enzyme for regulating the intracellular polyamines biosynthesis. Studies have confirmed that tumorigenesis is related to the imbalance of polyamines metabolism, also over-expression of oncogenes results in up-regulation of ODC, such as gastric cancer, prostate cancer, melanoma, breast cancer, and colorectal cancer. Moreover, ODC has become an target for anti-tumor therapy. In this study, we synthesized a new 18F-radiolabeled ornithine analogue and evaluated as a potential tumor PET tracer. Methods: The precursor compound was synthesized through the acylation of N-Boc-L-Ornithine tert-butyl ester and 2-bromopropionyl bromide. Nucleophilic substitution reaction of the precursor with [18F-] was proceeded at 100 °C for 30 min, the radiolabeled intermediate was purified by HPLC and hydrolyzed with 4 N hydrochloric acid. The radiolabeled ornithine [18F]FPO injection was obtained after the neutralization with an appropriate dose of 0.5 N NaHCO3. Bio-distribution and micro-PET/CT imaging studies were performed in normal ICR mice and nude mice bearing subcutaneous DU-145 cells, respectively. Results: Total synthesized time of [18F]FPO was about 80 min, and the radiochemical yield was about 5% (uncorrected, based on [18F]F-) and the radiochemical purity was>98%. The performance of micro-PET/CT imaging result showed that there was significant accumulation in tumor site for [18F]FPO, and the excellent high tumor/background was observed at 60 min. Bio-distribution in normal ICR mice demonstrated that the significantly lower uptakes in heart liver and brain was seen in comparison with other normal tissues. And the high uptake rate in kidney suggested that the urinary system is the main pathway to excrete, which is consistent with the consequence of PET/CT imaging. Conclusions: All the above results demonstrate that [18F]FPO has the potential of being a new PET tracer for tumor imaging.