287 (PB067) - Investigation of a novel radionuclide carrier for targeted radionuclide therapy

Abstract

Background: In internal radiation therapy of cancer, optimal targeting ligand and type of therapeutic radionuclide must be considered carefully for effective treatment. In addition, optimal ligand and nuclide type may vary depending on diverse parameters characterizing the tumor. Thus, for use in various cancers, there is a need for the development of a carrier that can firmly bind to a variety of nuclides. Here we introduce a biocompatible iron oxide nano radionuclide carrier. By reacting nanoparticles and nuclides using our conjugate synthesizer, it is possible to bind near-permanently nuclides to our nanocarriers. Material and methods: To test the carrier’s biocompatibility, particles were labeled with a fluorescence dye and injected intravenously into female CD-1 mice. Mice were anesthetized and carrier biodistribution was recorded. In addition, to test the carrier’s radionuclide binding capabilities, carriers were radiolabeled with radioactive iodine and injected intravenously in CD-1 mice that were anesthetized and scanned using single-photon emission computed tomography (SPECT). Ligand-mediated cellular uptake of the carriers was demonstrated per iron content in human origin cancer cells qualitatively through Prussian blue staining and quantitatively by ICP-MS. Results: As a result of biodistribution studies, carriers circulated through the body during initial time points were rapidly excreted through the kidney and could be detected in the bladder at 3 hours post-injection. Rapid excretion of carriers allows for lowered whole-body radiation toxicity. SPECT data showed stable distribution of radioactive iodine throughout the whole body. Given that the normal distribution of free radioiodine is for it to accumulate in the thyroid, such a result is evidence of firm binding of nuclides to the carrier. Ligand-receptor-mediated cellular uptake of nanocarriers increased dose-dependently up to 24 hours post-treatment. Conclusions: Here we have introduced a biocompatible radionuclide carrier. Its biodistribution and near-permanent nuclide binding properties make it an admirable platform for targeted radionuclide therapy. Further in vivo studies have been carried out to test the carrier’s application for treating triple-negative breast cancers (TNBC) and platinum-resistant ovarian cancers using131I and folic acid targeted ligands. No conflict of interest.