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

Although F-18-5-fluoro-N-(2-[diethylamino]-ethyl)picolinamide (F-18-5-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 F-18-5-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. F-18-PEG(3)-FPN was successfully prepared with a high radiolabeling yield (44.68% +/- 5.99%) and radiochemical purity (> 99%). The uptake of F-18-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 F-19-PEG(3)-FPN. On small animal PET images, B16F10 tumors, but not A375 tumors, were clearly delineated after F-18-PEG(3)-FPN injection. More importantly, F-18-PEG(3)-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 F-18-5-FPN, and the lesions in lung and liver could be clearly detected by F-18-PEG3-FPN PET imaging in mouse models of pulmonary or hepatic metastases. Overall, we successfully synthesized F-18-PEG(3)-FPN, which has higher labeling efficacy and better in vivo pharmacokinetics along with lower liver uptake compared to F-18-5-FPN. This suggests F-18-PEG(3)-FPN as a candidate for pigmented melanoma liver and lung metastasis detection.