In vivo detection of hydrogen sulfide in the brain of live mouse: application in neuroinflammation models

被引：12

作者：

Nam, Bora ^{[1
]}

Lee, Woonghee ^{[1
]}

Sarkar, Swarbhanu ^{[1
]}

Kim, Jae-Hong ^{[2
]}

Bhise, Abhinav ^{[1
]}

Park, Hyun ^{[3
]}

Kim, Jung Young ^{[3
]}

Huynh, Phuong Tu ^{[1
]}

Rajkumar, Subramani ^{[1
]}

Lee, Kiwoong ^{[1
]}

Ha, Yeong Su ^{[1
]}

Cho, Seong Hwan ^{[1
]}

Lim, Jeong Eun ^{[1
]}

Kim, Kyung Won ^{[1
]}

Lee, Kyo Chul ^{[3
]}

Suk, Kyoungho ^{[2
]}

Yoo, Jeongsoo ^{[1
]}

机构：

[1] Kyungpook Natl Univ, Sch Med, Brain Korea 21 Four KNU Convergence Educ Program, Dept Mol Med, Daegu 41944, South Korea

[2] Kyungpook Natl Univ, Sch Med, Brain Korea 21 Four KNU Convergence Educ Program, Dept Pharmacol, Daegu 41944, South Korea

[3] Korea Inst Radiol & Med Sci, Div Appl RI, Seoul 01812, South Korea

来源：

EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING | 2022年 / 49卷 / 12期

基金：

新加坡国家研究基金会;

关键词：

Imaging agent; Hydrogen sulfide; Gasotransmitter; Neuroinflammation; ALZHEIMERS-DISEASE; FLUORESCENT-PROBES; H2S; COPPER; BETA; METABOLISM; INHIBITORS; STRATEGY; SULFUR; TOOLS;

D O I：

10.1007/s00259-022-05854-1

中图分类号：

R8 [特种医学]; R445 [影像诊断学];

学科分类号：

1002 ; 100207 ; 1009 ;

摘要：

Purpose Hydrogen sulfide (H2S) plays important roles in brain pathophysiology. However, nuclear imaging probes for the in vivo detection of brain H2S in living animals have not been developed. Here, we report the first nuclear imaging probe that enables in vivo imaging of endogenous H2S in the brain of live mice. Methods Utilizing a bis(thiosemicarbazone) backbone, a fluorescent ATSM-FITC conjugate was synthesized. Its copper complex, Cu(ATSM-FITC) was thoroughly tested as a biosensor for H2S. The same ATSM-FITC ligand was quantitatively labeled with [Cu-64]CuCl2 to obtain a radioactive [Cu-64][Cu(ATSM-FITC)] imaging probe. Biodistribution and positron emission tomography (PET) imaging studies were performed in healthy mice and neuroinflammation models. Results The Cu(ATSM-FITC) complex reacts instantly with H2S to release CuS and becomes fluorescent. It showed excellent reactivity, sensitivity, and selectivity to H2S. Endogenous H2S levels in living cells were successfully detected by fluorescence microscopy. Exceptionally high brain uptake of [Cu-64][Cu(ATSM-FITC)] (> 9% ID/g) was observed in biodistribution and PET imaging studies. Subtle changes in brain H2S concentrations in live mice were accurately detected by quantitative PET imaging. Due to its dual modality feature, increased H2S levels in neuroinflammation models were characterized at the subcellular level by fluorescence imaging and at the whole-body scale by PET imaging. Conclusion Our biosensor can be readily utilized to study brain H2S function in live animal models and shows great potential as a novel imaging agent for diagnosing brain diseases.

引用

页码：4073 / 4087

页数：15