Preclinical study of a new 177Lu-labeled somatostatin receptor antagonist in HT-29 human colorectal cancer cells

Behnammanesh, Hossein and Erfani, Mostafa and Hajiramezanali, Maliheh and Jokar, Safura and Geramifar, Parham and Sabzevari, Omid and Amini, Mohsen and Mazidi, Mohammad and Beiki, Davood (2020) Preclinical study of a new 177Lu-labeled somatostatin receptor antagonist in HT-29 human colorectal cancer cells. Asia Oceania Journal of Nuclear Medicine and Biology, 8 (2). pp. 109-115.

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Abstract

Objective(s): Somatostatin receptor-positive neuroendocrine tumors have been targeted using various peptide analogs radiolabeled with therapeutic radionuclides for years. The better biomedical properties of radioantagonists as higher tumor uptake make these radioligands more attractive than agonists for somatostatin receptor-targeted radionuclide therapy. In this study, we tried to evaluate the efficiency of Luthetium-177 (177Lu) radiolabeled DOTA-Peptide 2 (177Lu-DOTA-Peptide 2) as a new radioantagonist in HT-29 human colorectal cancer in vitro and in vivo. Methods: DOTA conjugated antagonistic peptide with the sequence of p-Cl-Phe-Cyclo(D-Cys-L-BzThi-D-Aph-Lys-Thr-Cys)-D-Tyr-NH2 (DOTA-Peptide 2) was labeled with 177Lu. In vitro assays (saturation binding assay and internalization test) and animal biodistribution were performed in human colon adenocarcinoma cells (HT-29) and HT-29 tumor-bearing nude mice. Results: 177Lu-DOTA-Peptide 2 showed high stability in acetate buffer and human plasma (>97). Antagonistic property of 177Lu-DOTA-Peptide 2 was confirmed by low internalization in HT-29 cells (<5). The desired dissociation constant (Kd =11.14 nM) and effective tumor uptake (10.89 percentage of injected dose per gram of tumor) showed high binding affinity of 177Lu-DOTA-Peptide 2 to somatostatin receptors. Conclusion: 177Lu-DOTA-Peptide 2 demonstrated selective and high binding affinity to somatostatin receptors overexpressed on the surface of HT-29 cancer cells, which could make this radiopeptide suitable for somatostatin receptor-targeted radionuclide therapy.

Item Type: Article
Uncontrolled Keywords: Somatostatin,Lutetium-177,Antagonistic peptide,Human colon adenocarcinoma cells
Subjects: WN Radiology . Diagnostic Imaging
Divisions: Journals > Asia Oceania J Nuclear Medicine & Biology
Depositing User: AOJNMB AOJNMB
Date Deposited: 27 Jun 2020 08:46
Last Modified: 27 Jun 2020 08:46
URI: http://eprints.mums.ac.ir/id/eprint/19467

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