Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea; Isotope Production Division, Pakistan Institute of Nuclear Science & Technology (PINSTECH), P. O, Nilore, Islamabad, Pakistan.
Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea; Department of Biomedical Sciences, Seoul National University Graduate School, Seoul, Republic of Korea; Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
Bioorg Med Chem. 2019 May 15;27(10):1925-1931. doi: 10.1016/j.bmc.2019.04.013. Epub 2019 Apr 10.
Folate receptors (FR) are frequently overexpressed in a wide variety of human cancers. The aim of this study was to develop a trivalent Tc(CO)-labeled folate radiotracer containing isonitrile (CN-R) as the coordinating ligand for FR target imaging. [Tc]Tc-10 was HPLC purified (>98% chemical purity) and evaluated in vitro and in vivo as a potential agent for targeting FR-positive KB cells. [Tc]Tc-10 is a hydrophilic compound with partition coefficient of -2.90 ± 0.13 that showed high binding affinity (0.04 ± 0.002 nM) in vitro. High accumulation and retention of [Tc]Tc-10 (5.32 ± 2.99% ID/g) was observed in mice with KB tumors at 4 h after injection through the tail vein, which was significantly inhibited by co-injection of free folic acid (FA). SPECT (single photon emission tomography)/CT results were in accordance with biodistribution data at all time points.
叶酸受体（FR）在多种人类癌症中过度表达。本研究旨在开发一种三价 Tc（CO）标记的叶酸放射性示踪剂，其中异腈（CN-R）作为配位配体用于 FR 靶向成像。[Tc]Tc-10 经 HPLC 纯化（>98%化学纯度），并在体外和体内进行评估，作为靶向 FR 阳性 KB 细胞的潜在药物。[Tc]Tc-10 是一种具有 -2.90±0.13 分配系数的亲水性化合物，在体外表现出高结合亲和力（0.04±0.002 nM）。在通过尾静脉注射后 4 小时，注射部位存在 KB 肿瘤的小鼠中观察到 [Tc]Tc-10 的高积累和保留（5.32±2.99% ID/g），这一现象通过与游离叶酸（FA）共同注射可显著抑制。在所有时间点，SPECT（单光子发射断层扫描）/CT 结果均与生物分布数据一致。
