MRI Monitored Mn-THPPmPEG12-Guided Phototherapy Elicits Abscopal Immunity and Synergizes with PD-1 Blockade in Triple-Negative Breast Cancer in Mice Model.

PURPOSE: The study was to develop a clinical-translational theranostic photosensitizer, Mn-THPPmPEG12, for multiparametric MRI-monitored photodynamic therapy (PDT) of triple-negative breast cancer (TNBC), and to evaluate its potential to elicit abscopal immunity and synergize with PD-1 blockade.

METHODS

Mn-THPPmPEG12 was synthesized and characterized, and its MRI contrast capability was evaluated. A primary TNBC mouse model was established, and the PDT efficacy of Mn‑THPPmPEG12 was evaluated using intravoxel incoherent motion‑diffusion weighted imaging (IVIM‑DWI) and blood oxygen level‑dependent MRI (BOLD‑MRI), with final pathological analyses performed for validation. Subsequently, a bilateral TNBC mouse model was established to investigate the abscopal immune response in distant tumors following PDT of primary tumors, as well as the synergistic efficacy of combining PDT with anti‑PD‑1 blockade. Throughout the treatment, MRI served as a non-invasive method for real-time monitoring of therapeutic response.

RESULTS

Mn-THPPmPEG12 exhibited excellent water solubility and high T1 relaxivity (r1 = 4.47 mM-1·s-1). Mn-THPPmPEG12-mediated PDT significantly inhibited primary TNBC growth, with MRI parameters (D, D*, f, and R2*) correlating strongly with pathological findings. Notably, PDT triggered an abscopal effect in a bilateral TNBC mouse model, increasing CD8⁺ T cell infiltration and PD-1 expression in distant tumors. Combined with anti-PD-1 blockade, the therapy showed superior efficacy against both primary and distant tumors, with parameter D enabling early detection of treatment response.

CONCLUSION

Mn-THPPmPEG12 serves as a potent theranostic platform that enables precise MRI-monitored PDT. The PDT mediated by Mn-THPPmPEG12 elicits an abscopal immune effect and synergizes with PD-1 blockade to enhance TNBC treatment.