Synthesis and Evaluation of (99m)Tc-Labeled Dimeric Folic Acid for FR-Targeting

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 (99m)Tc using tricine and trisodium triphenylpho...

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Bibliographic Details
Published in:Molecules (Basel, Switzerland) Switzerland), 2016-06, Vol.21 (6)
Main Authors: Guo, Zhide, Gao, Mengna, Song, Manli, Shi, Changrong, Zhang, Pu, Xu, Duo, You, Linyi, Zhuang, Rongqiang, Su, Xinhui, Liu, Ting, Du, Jin, Zhang, Xianzhong
Format: Article
Language:English
Subjects:
Animals
Cell Line, Tumor
Folate Receptor 1 - antagonists & inhibitors
Folate Receptor 1 - chemistry
Folate Receptor 1 - metabolism
Folic Acid - chemistry
Folic Acid - metabolism
Humans
Mice
Neoplasms - drug therapy
Octreotide - analogs & derivatives
Octreotide - chemistry
Organophosphorus Compounds - chemistry
Organotechnetium Compounds - chemistry
Radiopharmaceuticals - chemistry
Sulfonic Acids - chemistry
Technetium - chemistry
Tissue Distribution
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Summary: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 (99m)Tc using tricine and trisodium triphenylphosphine-3,3',3″-trisulfonate (TPPTS) as coligands ((99m)Tc-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 (99m)Tc-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 (99m)Tc-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.
ISSN:1420-3049
DOI:10.3390/molecules21060817