N -(2-(dimethylamino)ethyl)-4- 18 F-fluorobenzamide: A Novel Molecular Probe for High-Contrast PET Imaging of Malignant Melanoma.

Malignant melanoma is a very aggressive and serious form of skin cancer, with prognosis and treatment outcome depending heavily on the clinical stage of the disease at the time of diagnosis. Here, we synthesized a novel 18 F-labeled benzamide derivative to target melanoma, and then evaluated its biological characteristics in small animal models. Methods : N -(2-(dimethylamino)ethyl)-4-18 F-fluorobenzamide (18 F-DMFB) was synthesized by reaction of N -succinimidyl 4-18 F-fluorobenzoate with N , N -dimethylethylenediamine. The binding affinity of 18 F-DMFB was measured in B16F10 (mouse melanoma) cells with or without L -tyrosine. MicroPET imaging with 18 F-DMFB was performed in B16F10 xenograft and metastasis mouse models. Results : The overall non-decay-corrected radiochemical yield of 18 F-DMFB was approximately 10%-15%. Uptake of 18 F-DMFB was melanin-specific as cellular uptake in B16F10 increased more than 18-fold in the presence of L -tyrosine. Biodistribution studies revealed that 18 F-DMFB accumulated, and was retained, in B16F10 xenografts for 120 min (10, 30, 60 and 120 min: 9.24, 10.80, 13.0, 10.59 %ID/g, respectively) of post-radiotracer injection. Liver uptake of 18 F-DMFB decreased from 10 to 120 min and showed fast clearance (10, 30, 60 and 120 min: 11.19, 5.7, 2.47, 0.4 %ID/g). Furthermore, 18 F-DMFB allowed visualization of metastatic lesions immediately after injection, and was retained in lesions for over 60 min, with a high tumor-to-background ratio. Conclusion : 18 F-DMFB demonstrated high melanin targeting ability and tumor-specific tumor uptake in both primary and metastatic lesions in animal models bearing malignant melanoma. 18 F-DMFB may be a potential PET imaging agent for melanoma.