Development of Radiofluorinated Nicotinamide/Picolinamide Derivatives as Diagnostic Probes for the Detection of Melanoma

Regarding the increased incidence and high mortality rate of malignant melanoma, practical early-detection methods are essential to improve patients’ clinical outcomes. In this study, we successfully prepared novel picolinamide–benzamide ((18)F-FPABZA) and nicotinamide–benzamide ((18)F-FNABZA) conjugates and determined their biological characteristics. The radiochemical yields of (18)F-FPABZA and (18)F-FNABZA were 26 ± 5% and 1 ± 0.5%, respectively. (18)F-FPABZA was more lipophilic (log P = 1.48) than (18)F-FNABZA (log P = 0.68). The cellular uptake of (18)F-FPABZA in melanotic B16F10 cells was relatively higher than that of (18)F-FNABZA at 15 min post-incubation. However, both radiotracers did not retain in amelanotic A375 cells. The tumor-to-muscle ratios of (18)F-FPABZA-injected B16F10 tumor-bearing mice increased from 7.6 ± 0.4 at 15 min post-injection (p.i.) to 27.5 ± 16.6 at 3 h p.i., while those administered with (18)F-FNABZA did not show a similarly dramatic increase throughout the experimental period. The results obtained from biodistribution studies were consistent with those derived from microPET imaging. This study demonstrated that (18)F-FPABZA is a promising melanin-targeting positron emission tomography (PET) probe for melanotic melanoma.