Sarah Johnson with Dr. Georges El Fakhri (MGH)
Radionuclide therapy is useful in the locoregional treatment of non-operable or marginally operable tumors. Starting with Feraheme (FH), a commercially available nanoparticle (NP) approved by the FDA for the treatment of iron anemia, Dr. El Fakhri’s lab has previously demonstrated success in creating a multifunctional NP for both imaging and therapy, in which they applied a combination of heat-induced radiolabeling (HIR) to add radioisotopes to the core of FH and surface coating click chemistry to attach cancer-targeting biomolecules. This integration functionalizes the radiolabeled FH NP for cancer targeting. HIR chemistry is a chelate-free Radiocation Surface Adsorption method and demonstrates cation flexibility, which allows the incorporation of multiple kinds of radioisotopes such as 89Zr4+, 64Cu2+ and 111In3+ for imaging and 90Y3+ and 177Lu3+ for therapy. 177Lu is a beta-emitting isotope that has been used to radiolabel other small cancer-specific molecules for effective radionuclide therapy, such as prostate-specific membrane antigen (PSMA) for the treatment of prostate cancer and DOTATATE for endocrine tumors. The focus of this project is to investigate the therapeutic efficacy of intra-/peri-tumoral injection of [177Lu]-FHNPs in a panel of human cancer and murine cancer cell line xenograft tumor-bearing mice. We will use the chelate-free HIR method to label FH NPs with 177Lu3+ and compare their tumor-killing efficacy when the NPs are with or without surface cancer-targeting biomolecules. Tumor growth inhibition will be monitored by caliper measurements of tumor size, followed by biodistribution studies to investigate normal organ toxicity. If successful, the [177Lu]-FHNP may be a promising tool for cancer therapy by locoregional application for non-surgically removable tumor elimination and/or pre-surgical tumor shrinking.
