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Molecules 2016, 21(6), 817;

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

Department of Isotopes, China Institute of Atomic Energy, P. O. Box 2108, Beijing 102413, China
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
Department of Nuclear Medicine, Zhongshan Hospital Affiliated of Xiamen University, Hubin South Road, Xiamen 361004, China
Authors to whom correspondence should be addressed.
Academic Editor: Zhen Cheng
Received: 30 May 2016 / Revised: 17 June 2016 / Accepted: 20 June 2016 / Published: 22 June 2016
(This article belongs to the Special Issue Molecular Imaging Probes)
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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. View Full-Text
Keywords: folate receptor; molecular imaging; dimeric folic acids; click reaction; SPECT imaging folate receptor; molecular imaging; dimeric folic acids; click reaction; SPECT imaging

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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Guo, Z.; Gao, M.; Song, M.; Shi, C.; Zhang, P.; Xu, D.; You, L.; Zhuang, R.; Su, X.; Liu, T.; Du, J.; Zhang, X. Synthesis and Evaluation of 99mTc-Labeled Dimeric Folic Acid for FR-Targeting. Molecules 2016, 21, 817.

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