Synthesis and Preclinical Evaluation of ¹⁸F-PEG₃-FPN for the Detection of Metastatic Pigmented Melanoma

Abstract

Although ¹⁸F-5-fluoro-N-(2-[diethylamino]ethyl)picolinamide (¹⁸F-5-FPN) is considered a promising radiopharmaceutical for PET imaging of melanoma, it accumulates at high concentrations in the liver. The aim in this research was to optimize the structure of ¹⁸F-5-FPN with triethylene glycol to reduce liver uptake as well as improve pharmacokinetics, and to evaluate its performance in detection of melanoma liver and lung metastases. ¹⁸F-PEG₃-FPN was successfully prepared with a high radiolabeling yield (44.68% ± 5.99%) and radiochemical purity (>99%). The uptake of ¹⁸F-PEG₃-FPN by pigmented B16F10 melanoma cells was significantly higher than that by amelanotic melanoma A375 cells. The binding to B16F10 cells could be blocked by excess ¹⁹F-PEG₃-FPN. On small animal PET images, B16F10 tumors, but not A375 tumors, were clearly delineated after ¹⁸F-PEG₃-FPN injection. More importantly, ¹⁸F-PEG₃-FPN uptake by liver (2.27 ± 0.45 and 1.74 ± 0.35% ID/g, at 1 and 2 h) was significantly lower than that of ¹⁸F-5-FPN, and the lesions in lung and liver could be clearly detected by ¹⁸F-PEG₃-FPN PET imaging in mouse models of pulmonary or hepatic metastases. Overall, we successfully synthesized ¹⁸F-PEG₃-FPN, which has higher labeling efficacy and better in vivo pharmacokinetics along with lower liver uptake compared to ¹⁸F-5-FPN. This suggests ¹⁸F-PEG₃-FPN as a candidate for pigmented melanoma liver and lung metastasis detection.