Radiopharmaceuticals that can target the random metastatic dissemination of
melanoma tumors may present opportunities for imaging and staging the disease as well as potential radiotherapeutic applications. A novel molecule, 2-(2-(4-(4-(123)I-iodobenzyl)piperazin-1-yl)-2-oxoethyl)isoindoline-1,3-dione (MEL037), was synthesized, labeled with 123I, and evaluated for application in
melanoma tumor scintigraphy and
radiotherapy.
METHODS: The
tumor imaging potential of 123I-MEL037 was studied in vivo in C57BL/6J female mice bearing the B16F0 murine
melanoma tumor and in BALB/c nude mice bearing the A375 human
amelanotic melanoma tumor by biodistribution, competition studies, and SPECT.
RESULTS: 123I-MEL037 exhibited high and rapid uptake in the B16F0
melanoma tumor at 1 h (13 %ID/g [percentage injected dose per gram]), increasing with time to reach 25 %ID/g at 6 h. A significant uptake was also observed in the eyes (2 %ID, at 3-6 h after injection) of black mice. No uptake was observed in the
tumor or in the eyes of nude mice bearing the A375
tumor. Because of high uptake and long retention in the
tumor and rapid body clearance, the mean contrast ratios (MCR) of 123I-MEL037 were 30 and 60, at 24 and 48 h after injection, respectively. At 24 h after injection of mice bearing the
B16 melanoma, SPECT indicated that the radioactivity was located predominately in the
tumor followed by the eyes, whereas no specific localization of the radioactivity was noted in mice bearing the A375 human amelanotic
tumor. In competition experiments, uptake of 123I-MEL037 in brain, lung, heart, and kidney--organs known to contain
sigma-receptors--was not significantly different in
haloperidol-treated animals compared with control animals. Therefore, reduction of uptake in
tumor and eyes of the pigmented mice bearing the B16F0
tumor suggested that the mechanism of
tumor uptake was likely due to an interaction with
melanin.
CONCLUSION: These findings suggested that 123I-MEL037, which displays a rapid and very high
tumor uptake, appeared to be a promising imaging agent for detection of most
melanoma tumors with the potential for development as a therapeutic agent in
melanoma tumor proliferation.