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

Autor: Fatemeh Ebrahimi, Nooshin Reisi Zargari, Mehdi Akhlaghi, S. Mohsen Asghari, Khosrou Abdi, Saeed Balalaie, Mahboobeh Asadi, Davood Beiki
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Pharmaceutics, Vol 16, Iss 7, p 899 (2024)
Druh dokumentu: article
ISSN: 1999-4923
DOI: 10.3390/pharmaceutics16070899
Popis: 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.
Databáze: Directory of Open Access Journals
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