Development of 99mTc-labeled trivalent isonitrile radiotracer for folate receptor imaging.

Folate receptors (FR) are frequently overexpressed in a wide variety of human cancers. The aim of this study was to develop a trivalent 99mTc(CO)3-labeled folate radiotracer containing isonitrile (CN-R) as the coordinating ligand for FR target imaging. [99mTc]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. [99mTc]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 [99mTc]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.