Northeastern University


Biology, '23

Hydrogel Sustained 177Lu-labeled Ferumoxytol Nanoparticles (177Lu-FH) for Intratumoral Injection Radionuclide Therapy

Mentor: Georges El Fakhri, Ph.D.

Institution: Massachusetts General Hospital

Recently, research utilizing radionuclide theranostic techniques has proved incredibly useful in both the treatment and imaging of various cancer types. Dr. El Fakhri’s lab has previously utilized ferumoxytol (brand name Feraheme, FH) nanoparticles (NPs), an FDA approved treatment for iron anemia, for these purposes, demonstrating the ability to utilize heat-induced radiolabeling (HIR) in the formulation of radionuclide-labeled FH NPs (Yuan et al., 2017). Specifically, members of Dr. El Fakhri’s lab have incorporated the radioisotope 177Lu3+ to the core surface of FH NPs, acting as a source to deliver beta radiation for the treatment of tumors. The therapeutic benefits of intratumorally injected 177Lu -FH NPs were observed in murine models, which showed increased cytotoxic activity in tumor cells compared to negative controls. However, biodistribution studies showed relatively high levels of radiation in various off-target sites, most notably bone and liver tissue, in these models. Along with potential detrimental effects to these off-target tissues, these findings imply that the delivery of beta radiation from 177Lu3+ radioisotopes could potentially be carried out more efficiently. To address this issue, we plan to utilize a thermosensitive hydrogel, a sustained drug release system consisting of a solution that, when injected and subjected to sufficient temperature, forms a gel in vivo. These gels degrade in the body over an extended period, which could significantly increase the amount of time over which 177Lu -FH NPs are able to act upon tumor cells, increasing their therapeutic efficacy. We will adapt a procedure described in a recently published paper which utilized a Pluronic F127/hyaluronic acid (PF127/HA) hydrogel for sustained NP-drug release in the treatment of iron overload to fit our experimental needs (Park et al., 2022). If successful, this 177Lu -FH hydrogel could significantly improve the therapeutic efficacy of intratumorally-injected radionuclide compounds for the treatment of cancer.