Melanin-Targeted Preclinical PET Imaging of Melanoma Metastasis

Dialkylamino-alkyl-benzamides possess an affinity for melanin, suggesting that labeling of such benzamides with F-18 could potentially produce melanin-targeted PET probes able to identify melanotic melanoma metastases in vivo with high sensitivity and specificity. Methods: In this study, N-[2-(diethylamino)-ethyl]-4-F-18-fluorobenzamide (F-18-FBZA) was synthesized via a 1-step conjugation reaction. The sigma-receptor binding affinity of F-19-FBZA was determined along with the in vitro cellular uptake of radiofluorinated F-18-FBZA in B16F10 cells. In vivo distribution and small-animal PET studies were conducted on mice bearing B16F10 melanoma, A375M amelanotic melanoma, and U87MG tumors, and comparative studies were performed with F-18-FDG PET in the melanoma models. Results: In vitro, uptake of F-18-FBZA was significantly higher in B16F10 cells treated with L-tyrosine (P < 0.001). In vivo, F-18-FBZA displayed significant tumor uptake; at 2 h, 5.94 +/- 1.83 percentage injected dose (%ID) per gram was observed in B16F10 tumors and only 0.75 +/- 0.09 %ID/g and 0.56 +/- 0.13 %ID/g was observed in amelanotic A375M and U87MG tumors, respectively. Lung uptake was significantly higher in murine lungs bearing melanotic B16F10 pulmonary metastases than in normal murine lungs (P < 0.01). Small-animal PET clearly identified melanotic lesions in both primary and pulmonary metastasis B16F10 tumor models. Coregistered micro-CT with small-animal PET along with biopsies further confirmed the presence of tumor lesions in the mouse lungs. Conclusion: F-18-FBZA specifically targets primary and metastatic melanotic melanoma lesions with high tumor uptake and may have translational potential.