Synthesis and Evaluation of 99mTc-Labeled Dimeric Folic Acid for FR-Targeting
Zhide Guo,
Mengna Gao,
Manli Song,
Changrong Shi,
Pu Zhang,
Duo Xu,
Linyi You,
Rongqiang Zhuang,
Xinhui Su,
Ting Liu,
Jin Du,
Xianzhong Zhang
Affiliations
Zhide Guo
Department of Isotopes, China Institute of Atomic Energy, P. O. Box 2108, Beijing 102413, China
Mengna Gao
Center for Molecular Imaging and Translational Medicine, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiang’an South Rd, Xiamen 361102, China
Manli Song
Center for Molecular Imaging and Translational Medicine, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiang’an South Rd, Xiamen 361102, China
Changrong Shi
Center for Molecular Imaging and Translational Medicine, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiang’an South Rd, Xiamen 361102, China
Pu Zhang
Center for Molecular Imaging and Translational Medicine, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiang’an South Rd, Xiamen 361102, China
Duo Xu
Center for Molecular Imaging and Translational Medicine, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiang’an South Rd, Xiamen 361102, China
Linyi You
Center for Molecular Imaging and Translational Medicine, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiang’an South Rd, Xiamen 361102, China
Rongqiang Zhuang
Center for Molecular Imaging and Translational Medicine, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiang’an South Rd, Xiamen 361102, China
Xinhui Su
Department of Nuclear Medicine, Zhongshan Hospital Affiliated of Xiamen University, Hubin South Road, Xiamen 361004, China
Ting Liu
Center for Molecular Imaging and Translational Medicine, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiang’an South Rd, Xiamen 361102, China
Jin Du
Department of Isotopes, China Institute of Atomic Energy, P. O. Box 2108, Beijing 102413, China
Xianzhong Zhang
Center for Molecular Imaging and Translational Medicine, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiang’an South Rd, Xiamen 361102, China
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.