Key Laboratory of Radiopharmaceuticals of Ministry of Education, NMPA (National Medical Products Administration) Key Laboratory for Research and Evaluation of Radiopharmaceuticals, College of Chemistry, Beijing Normal University, Beijing 100875, P. R. China.
Key Laboratory of Beam Technology of the Ministry of Education, School of Physics and Astronomy, Beijing Normal University, Beijing 100875, China.
J Med Chem. 2024 Sep 12;67(17):15796-15806. doi: 10.1021/acs.jmedchem.4c01425. Epub 2024 Jul 26.
F-2-fluoro-2-deoxy-d-glucose ([F]FDG) has been the most used positron emission tomography imaging agent for clinical applications. Single photon emission computed tomography (SPECT) imaging is cheaper and used more widely for diagnostic use, but there is no SPECT tumor imaging agent for clinical applications comparable to [F]FDG. Mannose is a C2 epimer of glucose and can also be transported into tumor cells via glucose transporters (GLUTs). To develop a novel SPECT tumor imaging agent with satisfactory tumor uptake and tumor/nontarget ratios, here a mannose derivative (CN7DM) was synthesized and radiolabeled with technetium-99m to prepare [Tc]Tc-CN7DM. The six-coordinated structure of [Tc]Tc-CN7DM was confirmed by the corresponding rhenium compound (Re-CN7DM). [Tc]Tc-CN7DM was transported into cancer cells via GLUTs and may be trapped in the cancer cells by electrostatic attraction. The probe exhibited high uptake in tumors and low uptake in nontarget tissues in mice bearing different tumors, indicating that [Tc]Tc-CN7DM exhibited promising potential for SPECT tumor imaging and warranted further clinical investigation.
氟代-2-脱氧-D-葡萄糖([F]FDG) 一直是临床应用中最常用的正电子发射断层扫描成像剂。单光子发射计算机断层扫描(SPECT) 成像价格更便宜，更广泛用于诊断用途，但没有与 [F]FDG 相当的用于临床应用的 SPECT 肿瘤成像剂。甘露糖是葡萄糖的 C2 差向异构体，也可以通过葡萄糖转运蛋白(GLUTs) 进入肿瘤细胞。为了开发一种具有令人满意的肿瘤摄取和肿瘤/非靶比值的新型 SPECT 肿瘤成像剂，在此合成了甘露糖衍生物 (CN7DM)，并用锝-99m 放射性标记以制备[Tc]Tc-CN7DM。[Tc]Tc-CN7DM 的六配位结构通过相应的铼化合物 (Re-CN7DM) 得到证实。[Tc]Tc-CN7DM 通过 GLUTs 进入癌细胞，可能通过静电吸引而被滞留在癌细胞中。探针在携带不同肿瘤的小鼠中表现出高肿瘤摄取和低非靶组织摄取，表明[Tc]Tc-CN7DM 具有用于 SPECT 肿瘤成像的巨大潜力，值得进一步临床研究。
