Development of Novel 99mTc-Labeled Hydrazinoicotinamide-Modified Ubiquicidin 29-41 Complexes with Improved Target-to-Nontarget Ratios for Bacterial Infection Imaging

IF 4.9 Q1 CHEMISTRY, MEDICINAL

ACS Pharmacology and Translational Science Pub Date : 2025-02-04 DOI:10.1021/acsptsci.4c0059910.1021/acsptsci.4c00599

Yuhao Jiang, Qianna Wang, Guangxing Yin, Junhong Feng, Qing Ruan, Peiwen Han and Junbo Zhang*,

{"title":"Development of Novel 99mTc-Labeled Hydrazinoicotinamide-Modified Ubiquicidin 29-41 Complexes with Improved Target-to-Nontarget Ratios for Bacterial Infection Imaging","authors":"Yuhao Jiang, Qianna Wang, Guangxing Yin, Junhong Feng, Qing Ruan, Peiwen Han and Junbo Zhang*, ","doi":"10.1021/acsptsci.4c0059910.1021/acsptsci.4c00599","DOIUrl":null,"url":null,"abstract":"To develop novel 99mTc-labeled ubiquicidin 29-41 derivatives for bacterial infection SPECT imaging aiming at achieving a high target-to-nontarget ratio and lower nontarget organ uptake, a novel 6-hydrazinoicotinamide (HYNIC) ubiquicidin 29-41 derivative (HYNIC-UBI 29-41) was designed and synthesized. It was then radiolabeled with ternary ligands, including TPPTS, PDA, 2,6-PDA, NIC, ISONIC, PSA, 4-PSA, and PES, to obtain eight 99mTc-labeled HYNIC-UBI 29-41 complexes. All the complexes demonstrated hydrophilicity, exhibited good in vitro stability, and specifically bound Staphylococcus aureus in vitro. Biodistribution studies in mice with bacterial infection demonstrated that [99mTc]Tc-tricine/TPPTS-HYNIC-UBI 29-41 resulted in increased abscess-to-muscle and abscess-to-blood ratios as well as decreased nontarget organ uptake. Furthermore, it was able to distinguish between bacterial infection and sterile inflammation. Single-photon emission computed tomography (SPECT) imaging studies in mice with bacterial infection revealed visible accumulation at the site of infection, indicating that [99mTc]Tc-tricine/TPPTS-HYNIC-UBI 29-41 is a potential radiotracer for imaging bacterial infection.","PeriodicalId":36426,"journal":{"name":"ACS Pharmacology and Translational Science","volume":"8 2","pages":"470–483 470–483"},"PeriodicalIF":4.9000,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"ACS Pharmacology and Translational Science","FirstCategoryId":"1085","ListUrlMain":"https://pubs.acs.org/doi/10.1021/acsptsci.4c00599","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}

引用次数: 0

Abstract

To develop novel ^99mTc-labeled ubiquicidin 29-41 derivatives for bacterial infection SPECT imaging aiming at achieving a high target-to-nontarget ratio and lower nontarget organ uptake, a novel 6-hydrazinoicotinamide (HYNIC) ubiquicidin 29-41 derivative (HYNIC-UBI 29-41) was designed and synthesized. It was then radiolabeled with ternary ligands, including TPPTS, PDA, 2,6-PDA, NIC, ISONIC, PSA, 4-PSA, and PES, to obtain eight ^99mTc-labeled HYNIC-UBI 29-41 complexes. All the complexes demonstrated hydrophilicity, exhibited good in vitro stability, and specifically bound Staphylococcus aureus in vitro. Biodistribution studies in mice with bacterial infection demonstrated that [^99mTc]Tc-tricine/TPPTS-HYNIC-UBI 29-41 resulted in increased abscess-to-muscle and abscess-to-blood ratios as well as decreased nontarget organ uptake. Furthermore, it was able to distinguish between bacterial infection and sterile inflammation. Single-photon emission computed tomography (SPECT) imaging studies in mice with bacterial infection revealed visible accumulation at the site of infection, indicating that [^99mTc]Tc-tricine/TPPTS-HYNIC-UBI 29-41 is a potential radiotracer for imaging bacterial infection.

Abstract Image

查看原文本刊更多论文

求助全文

约1分钟内获得全文求助全文

来源期刊

ACS Pharmacology and Translational Science Medicine-Pharmacology (medical)

CiteScore

10.00

自引率

3.30%

发文量

133

期刊介绍： ACS Pharmacology & Translational Science publishes high quality, innovative, and impactful research across the broad spectrum of biological sciences, covering basic and molecular sciences through to translational preclinical studies. Clinical studies that address novel mechanisms of action, and methodological papers that provide innovation, and advance translation, will also be considered. We give priority to studies that fully integrate basic pharmacological and/or biochemical findings into physiological processes that have translational potential in a broad range of biomedical disciplines. Therefore, studies that employ a complementary blend of in vitro and in vivo systems are of particular interest to the journal. Nonetheless, all innovative and impactful research that has an articulated translational relevance will be considered. ACS Pharmacology & Translational Science does not publish research on biological extracts that have unknown concentration or unknown chemical composition. Authors are encouraged to use the pre-submission inquiry mechanism to ensure relevance and appropriateness of research.