Synthesis and evaluation of a 68Ga-labeled iodinated benzamide derivative as a PET imaging agent for malignant melanoma

Abstract

Malignant melanoma is a highly aggressive skin cancer with increasing prevalence worldwide. The 5-year survival rate for localized malignant melanoma is 90%, but this drops to 6% if metastasis has occurred at diagnosis. Current positron emission tomography (PET) imaging probes, such as 2-deoxy-2-[18F]fluoro-D-glucose ([18F] FDG), show low sensitivity for metastatic melanoma, underscoring the need for new probes. This study explores the potential of 68Ga-labeled 2,2 ',2 '',2 & tprime;-(2-(4-(3-(2-((2-(5-iodopicolinamido)ethyl)(methyl)amino)ethyl)thiour- eido)benzyl)-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrayl)tetraacetic acid (68Ga-MI-0202F1) as a novel PET imaging probe designed for enhanced specificity and sensitivity towards melanin. The precursor MI-0202F1 was synthesized from 5-iodopicolinic acid, 2,2 '-diamino-N-methyldiethylamine, and 2,2 ',2 '',2 & tprime;-(2-(4-isothiocyanatobenzyl)-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrayl)tetraacetic acid ((p-SCN- Bn)-DOTA). The precursor was labeled with 68Ga in a reaction vial at 95 degrees C and pH 5.0 for 10 min. The radiochemical purity of the 68Ga-labeled compound was determined using radio-thin-layer chromatography. Cellular uptake of the iodinated benzamide derivative was evaluated in the B16F10 cell line (mouse melanoma) following L-tyrosine treatment. MicroPET studies were conducted at 30 and 60 min post-intravenous injection of the labeled complex into B16F10 tumor-bearing mice. The non-decay-corrected radiochemical yield was 95.96 +/- 3.73% (n = 3), and the radiochemical purity exceeded 98%. In vitro studies demonstrated significantly higher uptake of 68Ga-MI-0202F1 in L-tyrosine-treated B16F10 cells compared with untreated cells. In vivo PET imaging showed rapid accumulation and sustained retention of 68Ga-MI-0202F1 in melanoma tumors, with high tumor-to-background ratios. Overall, 68Ga-MI-0202F1 demonstrates potential as an innovative molecular imaging probe for malignant melanoma. Further studies are needed to investigate the potential of MI-0202F1 as a theranostic agent incorporating the radioisotope pairs 68Ga and 177Lu.