High-Contrast PET of Melanoma Using 18F-MEL050, a Selective Probe for Melanin with Predominantly Renal Clearance

The aim of this study was to evaluate the novel probe 18F-6-fluoro-N-[2-(diethylamino)ethyl] pyridine-3-carboxamide (18F-MEL050) for the imaging of primary and metastatic melanoma. Methods: PET using 18F-MEL050 was performed in murine models of melanoma. The specificity of 18F-MEL050 was studied by comparing its accumulation in pigmented B16-F0 allograft tumors with that of human amelanotic A375 xenografts using PET and high-resolution autoradiography. 18F-MEL050 PET results were compared with 18F-FDG PET, the current standard in melanoma molecular imaging. To test the ability of 18F-MEL050 to assess the metastatic spread of melanoma, a murine model of lung metastasis was imaged by PET/CT, and results correlated with physical assessment of tumor burden in the lungs. Results: In pigmented B16-F0 grafts, 18F-MEL050 PET yielded a tumor-to-background ratio of approximately 20:1 at 1 h and greater than 50:1 at 2 and 3 h. In the B16-F0 melanoma allograft model, tumor-to-background ratio was more than 9-fold higher for 18F-MEL050 than for 18F-FDG (50.9 ± 6.9 vs. 5.8 ± 0.5). No uptake was observed in the amelanotic melanoma xenografts. Intense uptake of 18F-MEL050 was evident in metastatic lesions in the lungs of B16-BL6 tumor–bearing mice on PET at 2 h after tracer injection, with high concordance between 18F-MEL050 accumulation on PET/CT and tumor burden determined at necroscopy. Conclusion:18F-MEL050 has a rapid tumor uptake and high retention with specificity for melanin, suggesting great potential for noninvasive clinical evaluation of suspected metastatic melanoma.