The Effects of Clinically Relevant Radionuclides on the Activation of an IFN1 Response Correlate with Radionuclide Half-life and Linear Energy Transfer and Influence Radiopharmaceutical Antitumor Efficacy.

ABSTRACT: Radiopharmaceutical therapies (RPT) activate an IFN1 response in tumor cells. We hypothesized that the timing and amplitude of this response varies by isotope. We compared equal doses delivered by 90Y, 177Lu, and 225Ac in vitro as unbound radionuclides and in vivo when chelated to NM600, a tumor-selective alkylphosphocholine. Response in murine MOC2 head and neck carcinoma and B78 melanoma was evaluated by using qPCR and flow cytometry. Therapeutic response to 225Ac-NM600 + anti-CTLA4 + anti-PD-L1 immune checkpoint inhibition (ICI) was evaluated in wild-type and stimulator of IFN genes (STING) knockout B78. The timing and magnitude of the IFN1 response correlated with radionuclide half-life and linear energy transfer. The ratio of CD8+ T cells to regulatory T cells increased in tumors 7 da

SUBMITTER: Kerr CP 

PROVIDER: S-EPMC12316559 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature