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

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Behnammanesh Hossein; ERFANI MOSTAFA; Hajiramezanali Maliheh; Jokar Safura; GERAMIFAR PARHAM; SABZEVARI OMID; AMINI MOHSEN; Mazidi Seyed Mohammad; BEIKI DAVOOD

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Journal: Asia Oceania Journal of Nuclear Medicine & Biology Year:2020 | Volume:8 | Issue:2 Page(s): 109-115

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Title

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

Author(s)

Keywords

Somatostatin Lutetium

177 Antagonistic peptide Human colonadenocarcinoma cells

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-DOTAPeptide 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.

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APA: Copy

Behnammanesh, Hossein, ERFANI, MOSTAFA, Hajiramezanali, Maliheh, Jokar, Safura, GERAMIFAR, PARHAM, SABZEVARI, OMID, AMINI, MOHSEN, Mazidi, Seyed Mohammad, & 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), 109-115. SID. https://sid.ir/paper/762766/en

Vancouver: Copy

Behnammanesh Hossein, ERFANI MOSTAFA, Hajiramezanali Maliheh, Jokar Safura, GERAMIFAR PARHAM, SABZEVARI OMID, AMINI MOHSEN, Mazidi Seyed Mohammad, BEIKI DAVOOD. 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[Internet]. 2020;8(2):109-115. Available from: https://sid.ir/paper/762766/en

IEEE: Copy

Hossein Behnammanesh, MOSTAFA ERFANI, Maliheh Hajiramezanali, Safura Jokar, PARHAM GERAMIFAR, OMID SABZEVARI, MOHSEN AMINI, Seyed Mohammad Mazidi, and DAVOOD BEIKI, “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, vol. 8, no. 2, pp. 109–115, 2020, [Online]. Available: https://sid.ir/paper/762766/en

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