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

Sang Hee Lee; Ji Young Choi; Jae Ho Jung; In Ho Song; Hyun Soo Park; Nunzio Denora; Francesco Leonetti; Sang Eun Kim; Byung Chul Lee

doi:10.3390/cancers13195029

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

Cancers (Basel). 2021 Oct 8;13(19):5029. doi: 10.3390/cancers13195029.

Authors

Sang Hee Lee^{1

2}, Ji Young Choi¹, Jae Ho Jung¹, In Ho Song¹, Hyun Soo Park¹, Nunzio Denora³, Francesco Leonetti³, Sang Eun Kim^{1

4

5}, Byung Chul Lee^{1

4}

Affiliations

¹ Department of Nuclear Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam 13620, Korea.
² Department of Transdisciplinary Studies, Graduate School of Convergence Science and Technology, Seoul National University, Seoul 08826, Korea.
³ Department of Pharmacy-Pharmaceutical Sciences, University of Bari "A. Moro", 70121 Bari, Italy.
⁴ Center for Nanomolecular Imaging and Innovative Drug Development, Advanced Institute of Convergence Technology, Suwon 16229, Korea.
⁵ Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul 08826, Korea.

Abstract

Cell adhesion receptor integrin α_vβ₃ 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 ¹⁸⁸Re-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 ^99mTc-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.

Keywords: combination therapy; peptide receptor radionuclide therapy; temozolomide; tumor angiogenesis.

Abstract

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