Synthesis and Evaluation of 99mTc-Labeled Dimeric Folic Acid for FR-Targeting

• Main Authors: Zhide Guo, Mengna Gao, Manli Song, Changrong Shi, Pu Zhang, Duo Xu, Linyi You, Rongqiang Zhuang, Xinhui Su, Ting Liu, Jin Du, Xianzhong Zhang
• Format: Article
• Language: English
• Published: MDPI AG 2016-06-01
• Series: Molecules
• Subjects: folate receptor; molecular imaging; dimeric folic acids; click reaction; SPECT imaging
• Online Access: http://www.mdpi.com/1420-3049/21/6/817

The folate receptor (FR) is overexpressed in a wide variety of human tumors. In our study, the multimeric concept was used to synthesize a dimeric folate derivative via a click reaction. The novel folate derivative (HYNIC-D1-FA2) was radiolabeled with 99mTc using tricine and trisodium triphenylphosphine-3,3′,3″-trisulfonate (TPPTS) as coligands (99mTc-HYNIC-D1-FA2) and its in vitro physicochemical properties, ex vivo biodistribution and in vivo micro-SPECT/CT imaging as a potential FR targeted agent were evaluated. It is a hydrophilic compound (log P = −2.52 ± 0.13) with high binding affinity (IC50 = 19.06 nM). Biodistribution in KB tumor-bearing mice showed that 99mTc-HYNIC-D1-FA2 had high uptake in FR overexpressed tumor and kidney at all time-points, and both of them could obviously be inhibited when blocking with free FA in the blocking studies. From the in vivo micro-SPECT/CT imaging results, good tumor uptake of 99mTc-HYNIC-D1-FA2 was observed in KB tumor-bearing mice and it could be blocked obviously. Based on the results, this new radiolabeled dimeric FA tracer might be a promising candidate for FR-targeting imaging with high affinity and selectivity.