Biodistribution of Modular Nanotransporter Carrying Auger Electron Emitter and Targeted at Melanoma Cells in Murine Tumor Model

摘要

Recombinant modular nanotransporter containing α-melanocyte-stimulating hormone peptide sequence (MNT-MSH) as a ligand module was designed for nucleus-targeted delivery of cytotoxic agents into melanoma cells. MNT-MSH radiolabeled with Auger electron emitter (~(111) In-NOTA-MNT-MSH) showed a high antitumor efficacy in mice bearing syngeneic melanoma after intratumoral (i.t.) injection. This study is aimed at evaluating the biodistribution of the radioconjugate in melanoma tumor model in vivo. _(111)In-NOTA-MNT-MSH was administered i.t. in C57Bl/6j mice bearing subcutaneously implanted B16-F1 murine melanoma cells, expressing high levels of MCR1. The tissue uptake of radioactivity was determined ex vivo by y-counter measurements. The intravenous route of administration did not provide a desirable level of radioactivity accumulation in the tumor, possibly, due to a high uptake of the transporter in liver tissue. After i. t. administration ~(111)In-NOTA-MNT-MSH provided a high local retention of radionuclide, ranged from 400 to 350 %ID/g within at least 48 hours post-injection. MNT containing Auger electron emitter and a-MSH peptide as vector ligand could be a promising basis for radiopharmaceutical preparations intended for melanoma treatment.