Integrin-αvβ3 is a therapeutically targetable fundamental factor in medulloblastoma tumorigenicity and radioresistance.

Medulloblastoma (MB) is one of the most prevalent solid tumors found in children, occuring in the brain's posterior fossa. The standard treatment protocol involves maximal resection surgery followed by craniospinal irradiation and chemotherapy. Despite a long-term survival rate of 70%, wide disparities among patients have been observed. The identification of pertinent targets for both initial and recurrent MB cases is imperative. Both primary and recurrent MBs are marked by their aggressive infiltration into surrounding brain tissue, robust angiogenesis, and resistance to radiation therapy. While the significant role of integrin-αvβ3 in driving these characteristics has been extensively documented in glioblastoma, its impact in the context of MB remains largely unexplored. Integrin-αvβ3 was found to be expressed in a subset of MB patients. We investigated the role of integrin-αvβ3 using MB-derived cell lines with β3-subunit depletion or overexpression both in vitro and in vivo settings. By generating radioresistant MB cell lines, we uncovered an increased integrin-αvβ3 expression, which correlated with increased susceptibility to pharmacological integrin-αvβ3 inhibition with cilengitide, a competitive ligand mimetic. Lastly, we conducted single-photon emission computed tomography (SPECT)/magnetic resonance imaging (MRI) studies on orthotopic models using a radiolabeled integrin-αvβ3 ligand (99mTc-RAFT-RGD. This innovative approach presents the potential for a novel predictive imaging technique in the realm of MB. Altogether, our findings lay the foundation for employing SPECT/MRI to identify a specific subset of MB patients eligible for integrin-αvβ3-directed therapies. This breakthrough offers a pathway toward more targeted and effective interventions in the treatment of MB.