The novel [⁶⁸Ga]Ga-DOTA-C6-anti-integrin peptide in glioblastoma

Glioblastoma (GB) is the most aggressive primary brain tumor. Patient survival remains poor, with current therapies bringing no improvements, and the assessment of therapy response and tumor progression using conventional imaging exams is challenging for clinicians during patient follow-up. Integrins, transmembrane proteins related to cell invasion and motility, are overexpressed in GB. This study evaluates the effects of [⁶⁸Ga]Ga-DOTA-C6-anti-integrin peptide on GB binding, internalization, survival, migration, and biodistribution, as well as its mechanism of action against the tumor. Binding and internalization assays performed in U87, U118, U251, and Gl261 GB cells at 30 minutes revealed binding rates of 8.0%, 3.9%, 6.0%, and 8.6%, and internalization of 9.4%, 7.0%, 8.1%, and 10.2%, respectively. At 60 minutes, the binding percentages were 7.8%, 3.9%, 4.7%, and 10.7%, while internalization was 9.8%, 6.7%, 6.6%, and 9.6%, respectively. The anti-integrin peptide did not affect proliferation, the cell cycle, or apoptosis, but reduced U251 and Gl261 cell migration compared to the control (63.1% vs. 85.8%, p = 0.03; 34.1% vs. 50.8%, p = 0.04, respectively). In U87 cells, the compound modulated the PI3K/Akt pathway, reducing expression of the ITGAV, AKT1, CCNE1, JUN, MDM2, and SRC genes and increasing CASP9 expression. Biodistribution analysis performed using PET/CT imaging in female Swiss mice showed that the [⁶⁸Ga]Ga-DOTA-C6-anti-integrin was eliminated by the kidneys and accessed the brain within the first few minutes after drug administration. Our data support the potential of [⁶⁸Ga]Ga-DOTA-C6-anti-integrin peptide as an imaging probe for GB and provide a basis for its further investigation as a candidate for therapeutic applications.