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Preclinical Evaluation of a Novel 99mTc-Labeled CB86 for Rheumatoid Arthritis Imaging.


ABSTRACT: 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.

SUBMITTER: Liu P 

PROVIDER: S-EPMC7745438 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Preclinical Evaluation of a Novel <sup>99m</sup>Tc-Labeled CB86 for Rheumatoid Arthritis Imaging.

Liu Peng P   Wang Tingting T   Yang Rongshui R   Dong Wentao W   Wang Qiang Q   Guo Zhide Z   Ma Chao C   Wang Weixing W   Li Huaibo H   Su Xinhui X  

ACS omega 20201130 49


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 (<sup>99m</sup>Tc)-labeled TSPO ligand (<sup>99m</sup>Tc-CB256 [2-(8-(2-(bis(pyridin-2-yl)methyl)amino)acetamido)-2-(4-chlorophenyl)<i>H</i>-imidazo[1,2-<i>a</i>]pyridin-3-yl)-<i>N</i>,<i>N</i>-dipropylacetamide] composed of a translocator protein (TSPO) ligand CB86 [[2-(4-chlorophenyl)-8-amino-imidazo[1,2-<i>a</i>  ...[more]

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