Tc-99m labeled PSMA-617 as a potential SPECT radiotracer for prostate cancer diagnostics: Complexation optimization and its in vitro/vivo evaluation

IF 3.3 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Bioorganic & Medicinal Chemistry Pub Date : 2025-02-01 DOI:10.1016/j.bmc.2024.118058

Kalapaphuk Tachatumvitoon , Charasphat Preuksarattanawut , Thititip Tippayamontri , Piyachai Khomein

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Abstract

Technetium-99m (Tc-99m) is the most employed radionuclide in nuclear imaging diagnostics worldwide for many diseases. The ideal physiochemical properties of Tc-99m (such as half-life and pure gamma energy) make it favorable for Single Photon Emission Computed Tomography (SPECT). In this study, we aim to expand the utilization of Tc-99m radiopharmaceutical toward prostate cancer diagnostics which is currently no FDA approved products and has been intensively examined for a potential candidate. The new formulation for Tc-99m complexation with PSMA-617, a current ligand for radionuclide therapy of prostate cancer with lutetium-177 (Lu-177), has been investigated. Co-complexation with citrate was utilized to improve the labeling efficiency by over 97 %. The stability of the new radiopharmaceutical was in vitro evaluated confirming that the Tc-99m labeled PSMA-617 remained stable for over a single half-life of Tc-99m in normal saline solution and in human serum. The in vivo study in the LNCaP xenografted mouse model confirmed a high selectivity of the new tracer toward prostate cancer.

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Tc-99m标记PSMA-617作为前列腺癌诊断的潜在SPECT放射示踪剂：络合优化及其体外/体内评价

锝-99m （Tc-99m）是世界上许多疾病的核成像诊断中使用最多的放射性核素。Tc-99m理想的物理化学性质（如半衰期和纯γ能量）使其有利于单光子发射计算机断层扫描（SPECT）。在本研究中，我们的目标是扩大Tc-99m放射性药物在前列腺癌诊断中的应用，Tc-99m目前还没有获得FDA批准的产品，并且已经在为潜在的候选产品进行深入研究。研究了Tc-99m与PSMA-617络合的新配方，PSMA-617是目前用镥-177 （Lu-177）治疗前列腺癌的配体。利用与柠檬酸盐的共络合使标记效率提高97%以上。新的放射性药物的稳定性进行了体外评估，确认Tc-99m标记的PSMA-617在正常生理盐水溶液和人血清中保持稳定超过Tc-99m的单个半衰期。在LNCaP异种移植小鼠模型的体内研究证实了这种新型示踪剂对前列腺癌的高选择性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Bioorganic & Medicinal Chemistry 医学-生化与分子生物学

CiteScore

6.80

自引率

2.90%

发文量

413

审稿时长

17 days

期刊介绍： Bioorganic & Medicinal Chemistry provides an international forum for the publication of full original research papers and critical reviews on molecular interactions in key biological targets such as receptors, channels, enzymes, nucleotides, lipids and saccharides. The aim of the journal is to promote a better understanding at the molecular level of life processes, and living organisms, as well as the interaction of these with chemical agents. A special feature will be that colour illustrations will be reproduced at no charge to the author, provided that the Editor agrees that colour is essential to the information content of the illustration in question.