A MALIGNANT-MELANOMA IMAGING AGENT - SYNTHESIS, CHARACTERIZATION, IN-VITRO BINDING AND BIODISTRIBUTION OF ODINE-125-(2-PIPERIDINYLAMINOETHYL)4-IODOBENZAMIDE

In order to develop improved radiopharmaceuticals for imaging malignan t melanoma, we have synthesized and characterized I-125- and I-131-lab eled (2-piperidinylaminoethyl) 4-iodobenzamide (PAB). In vitro binding profiles of IPAB and N-(2-diethylaminoethyl) 4-iodobenzamide (IDAB, a structurally related analog of IPAB) for a variety of neurotransmitte r receptors suggested that both IPAB and IDAB possessed a high sigma-1 affinity and a low affinity for sigma-e sites. In vitro homologous co mpetition binding studies of [(125)l]PAB with human malignant melanoma cell A2058 showed that the tracer was bound to the cells with a high affinity (Ki = 6.0 nM) and that the binding was saturable. Biodistribu tion studies in nude mice implanted with human malignant melanoma xeno grafts showed good tumor uptake (3.87% ID/g at 1 hr, 2.91% ID/g at 6 h r and 1.02% ID/g at 24 hr) of [(125)l]PAB. High tumor-to-nontarget org an ratios were obtained at 24 hr postinjection. Tumor-to-blood, liver, muscle, lung, intestines, heart and brain ratios at 24 hr were 17.80, 3.88, 94.58, 14.29, 10.87, 37.07 and 90.01, respectively. Tumor imagi ng with [I-131]PAB in a nude mice model xenografted with human maligna nt melanoma at 24 hr clearly delineated the tumor with very little act ivity in any other organ. These results demonstrate that sigma-1 recep tors could be used as external markers for malignant melanoma.