Dataset Information

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

ABSTRACT: 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-D?-FA?) was radiolabeled with (99m)Tc using tricine and trisodium triphenylphosphine-3,3',3?-trisulfonate (TPPTS) as coligands ((99m)Tc-HYNIC-D?-FA?) 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-D?-FA? 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-D?-FA? 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.

SUBMITTER: Guo Z

PROVIDER: S-EPMC6274367 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature

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

Guo Zhide Z Gao Mengna M Song Manli M Shi Changrong C Zhang Pu P Xu Duo D You Linyi L Zhuang Rongqiang R Su Xinhui X Liu Ting T Du Jin J Zhang Xianzhong X

Molecules (Basel, Switzerland) 20160622 6

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 target ...[more]

PMID: 27338334

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Project description:Early diagnosis and therapy are crucial to control disease progression optimally and achieve a good prognosis in rheumatoid arthritis (RA). Previous study showed that a technetium-99m (99mTc)-labeled TSPO ligand (99mTc-CB256 [2-(8-(2-(bis(pyridin-2-yl)methyl)amino)acetamido)-2-(4-chlorophenyl)H-imidazo[1,2-a]pyridin-3-yl)-N,N-dipropylacetamide] composed of a translocator protein (TSPO) ligand CB86 [[2-(4-chlorophenyl)-8-amino-imidazo[1,2-a]-pyridin-3-yl]-N,N-di-n-propylacetamide] and di-(2-picolyl)amine, a bifunctional chelate agent, was used to image a TSPO-rich cancer cell in vitro; however, few 99mTc-CB256 in vivo evaluation has been reported so far probably due to the cytotoxicity of CB256 (ca. 75 times more than analogous CB86). Herein, we describe a novel TSPO targeting radiopharmaceutical consisting of CB86 and diethylenetriaminepentaacetic acid (DTPA), a conventional bifunctional chelating ligand in clinical trials used to prepare 99mTc-labeled CB86, and its evaluation as a 99mTc-single-photon emission computed tomography (SPECT) probe. The radiosynthesis and characterization of 99mTc-DPTA-CB86 including hydrophilicity and stability tests were determined. Additionally, the binding affinity and specificity of 99mTc-DTPA-CB86 to TSPO were evaluated using RAW264.7 macrophage cells. Biodistribution and 99mTc-SPECT studies were conducted on rheumatoid arthritis (RA) rat models after the injection of 99mTc-DTPA-CB86 with or without co-injection of unlabeled DTPA-CB86. The radiosynthesis of 99mTc-DTPA-CB86 was completed successfully with the labeling yields and radiochemical purity of 95.86 ± 2.45 and 97.45 ± 0.69%, respectively. The probe displayed good stability in vitro and binding specificity to RAW264.7 macrophage cells. In the biodistribution studies, 99mTc-DTPA-CB86 exhibited rapid inflammatory ankle accumulation. At 180 min after administration, 99mTc-DTPA-CB86 uptakes of the left inflammatory ankle were 2.35 ± 0.10 percentage of the injected radioactivity per gram of tissue (% ID/g), significantly higher than those of the normal tissues. 99mTc-SPECT imaging studies revealed that 99mTc-DTPA-CB86 could clearly identify the left inflammatory ankle with good contrast at 30-180 min after injection. Therefore, 99mTc-DTPA-CB86 may be a promising probe for arthritis 99mTc-SPECT imaging.

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Dataset Information

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

Publications

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

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