Effect of Peptide Receptor Radionuclide Therapy in Combination with Temozolomide against Tumor Angiogenesis in a Glioblastoma Model

SIMPLE SUMMARY: Glioblastoma multiforme (GBM) is an aggressive brain tumor characterized by intense angiogenesis. Thus, tumor angiogenesis-related receptors, such as the cell adhesion molecule integrin α(v)β(3), are potential biomarkers for cancer diagnosis and therapy. In this study, we aimed to investigate the therapeutic efficacy of peptide receptor radionuclide therapy (PRRT) with (188)Re-IDA-D-[c(RGDfK)](2) (11.1 MBq). Our results revealed that PRRT combined with temozolomide markedly reduced the tumor volume compared with monotherapy. In summary, (188)Re-IDA-D-[c(RGDfK)](2) might be an effective radiotherapeutic agent for the treatment of GBM. ABSTRACT: Cell adhesion receptor integrin α(v)β(3) is a promising biomarker for developing tumor-angiogenesis targeted theranostics. In this study, we aimed to examine the therapeutic potential of peptide receptor radionuclide therapy (PRRT) with (188)Re-IDA-D-[c(RGDfK)](2) (11.1 MBq). The results showed that the tumor volume was significantly decreased by 81% compared with the vehicle-treated group in U87-MG xenografts. The quantitative in vivo anti-angiogenic responses of PRRT were obtained using (99m)Tc-IDA-D-[c(RGDfK)](2) SPECT and corresponded to the measured tumor volume. PRRT combined with temozolomide (TMZ) resulted in a 93% reduction in tumor volume, which was markedly greater than that of each agent used individually. In addition, histopathological characterization showed that PRRT combined with TMZ was superior to PRRT or TMZ alone, even when TMZ was used at half dose. Overall, our results indicated that integrin-targeted PRRT and TMZ combined therapy might be a new medical tool for the effective treatment of glioblastoma.