Synthesis, Radiolabeling, and Biodistribution Study of a Novel DOTA-Peptide for Targeting Vascular Endothelial Growth Factor Receptors in the Molecular Imaging of Breast Cancer

Author:

Ebrahimi Fatemeh1,Zargari Nooshin Reisi2,Akhlaghi Mehdi3ORCID,Asghari S. Mohsen4ORCID,Abdi Khosrou1ORCID,Balalaie Saeed5ORCID,Asadi Mahboobeh3,Beiki Davood13ORCID

Affiliation:

1. Department of Nuclear Pharmacy, School of Pharmacy, Tehran University of Medical Sciences, Tehran 1417614411, Iran

2. University Campus II, University of Guilan, Rasht 4144784475, Iran

3. Research Center for Nuclear Medicine, Shariati Hospital, Tehran University of Medical Sciences, Tehran 1411713135, Iran

4. Institute of Biochemistry and Biophysics (IBB), University of Tehran, Tehran 1417614335, Iran

5. Peptide Chemistry Research Institute, K. N. Toosi University of Technology, Tehran 158754416, Iran

Abstract

As angiogenesis plays a pivotal role in tumor progression and metastasis, leading to more cancer-related deaths, the angiogenic process can be considered as a target for diagnostic and therapeutic applications. The vascular endothelial growth factor receptor-1 (VEGR-1) and VEGFR-2 have high expression on breast cancer cells and contribute to angiogenesis and tumor development. Thus, early diagnosis through VEGFR-1/2 detection is an excellent strategy that can significantly increase a patient’s chance of survival. In this study, the VEGFR1/2-targeting peptide VGB3 was conjugated with 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), using 6-aminohexanoic acid (Ahx) as a spacer to prevent steric hindrance in binding. DOTA-Ahx-VGB3 was radiolabeled with Gallium-68 (68Ga) efficiently. An in vitro cell binding assay was assessed in the 4T1 cell line. The tumor-targeting potential of [68Ga]Ga-DOTA-Ahx-VGB3 was conducted for 4T1 tumor-bearing mice. Consequently, high radiochemical purity [68Ga]Ga-DOTA-Ahx-VGB3 (RCP = 98%) was prepared and stabilized in different buffer systems. Approximately 17% of the radiopeptide was internalized after 2 h incubation and receptor binding as characterized by the IC50 value being about 867 nM. The biodistribution and PET/CT studies revealed that [68Ga]Ga-DOTA-Ahx-VGB3 reached the tumor site and was excreted rapidly by the renal system. These features convey [68Ga]Ga-DOTA-Ahx-VGB3 as a suitable agent for the noninvasive visualization of VEGFR-1/2 expression.

Funder

the Tehran University of Medical Sciences

the Institute of Biochemistry and Biophysics

University of Tehran

Publisher

MDPI AG

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