Efficacy of 177Lu- and 90Y-labeled nanoparticles in targeted tumor therapy in a mouse CT26 and 4T1 xenograft model

Dragana Stanković; Drina Janković; Marija Mirković; Magdalena Radović; Zorana Milanović; Aleksandar Vukadinović; Aljoša Stanković; Marko Perić; Sanja Vranješ-Djurić; Željko Prijović; Miroslav Savić

Dragana Stanković University of Belgrade – Vinča Institute of Nuclear Sciences, Laboratory for radioisotopes
Drina Janković University of Belgrade – Vinča Institute of Nuclear Sciences, Laboratory for radioisotopes
Marija Mirković University of Belgrade – Vinča Institute of Nuclear Sciences, Laboratory for radioisotopes
Magdalena Radović University of Belgrade – Vinča Institute of Nuclear Sciences, Laboratory for radioisotopes
Zorana Milanović University of Belgrade – Vinča Institute of Nuclear Sciences, Laboratory for radioisotopes
Aleksandar Vukadinović University of Belgrade – Vinča Institute of Nuclear Sciences, Laboratory for radioisotopes
Aljoša Stanković University of Belgrade – Vinča Institute of Nuclear Sciences, Laboratory for radioisotopes
Marko Perić University of Belgrade – Vinča Institute of Nuclear Sciences, Laboratory for radioisotopes
Sanja Vranješ-Djurić University of Belgrade – Vinča Institute of Nuclear Sciences, Laboratory for radioisotopes
Željko Prijović University of Belgrade – Vinča Institute of Nuclear Sciences, Laboratory for radioisotopes
Miroslav Savić University of Belgrade – Faculty of Pharmacy, Department of Pharmacology

Abstract

Nanoparticle delivery to solid tumors after an intravenous injection has shown to be very limited in its ability to achieve therapeutic dosage in the tumor due to nonspecific nanoparticle uptake by RES. To overcome these problems, local intratumoral injection of nanoparticles is being investigated as more relevant route of administration. In the present study, superparamagnetic iron oxide nanoparticles (SPIONs) were synthetized, coated with citric (CA) or dimercaptosuccinic acid (DMSA) and radiolabeled with ⁹⁰Y or ¹⁷⁷Lu, aiming to develop radioactive nanoparticles for localized tumor therapy. Biodistribution and antitumor efficacy of radiolabeled SPIONs after local intratumoral administration in CT26 or 4T1 xenografts-bearing BALB/c mice were studied. Tracking the radioactivity distribution of injected ⁹⁰Y-CA-SPIONs and ¹⁷⁷Lu-DMSA-SPIONs revealed that due to the size of the nanoparticles, their diffusive escape from the tumor into healthy organs and tissues is slowed down; the particles remain at the injection site up to 14 days after the injection, and thereby increasing the tumor's exposure to radiation. Lower therapeutic efficacy of ¹⁷⁷Lu-DMSA-SPIONs in CT26 or 4T1 tumor can be explained by slight diffusion of particles from injection sites into distant tumor regions and moderate-energy β-particles emitted by ¹⁷⁷Lu (0.5MeV). These studies suggest that ⁹⁰Y-CA-SPIONs is superior to ¹⁷⁷Lu-DMSA-SPIONs at inhibiting both tumors growth, due to the high-energy β-particles emitted by ⁹⁰Y (2.27MeV) and a longer path length.⁹⁰Y is therapeutically superior to ¹⁷⁷Lu in investigated xenograft models. We believe that an intratumorally injected radiolabeled SPIONs can be considered as a potential therapeutic agent for localized cancer therapy.