Journal article
High-Contrast Detection of Somatostatin Receptor Subtype‑2 for Fluorescence-Guided Surgery
Molecular pharmaceutics, Vol.19(11), pp.4241-4253
11/07/2022
DOI: 10.1021/acs.molpharmaceut.2c00583
PMCID: PMC9830638
PMID: 36174110
Abstract
Dye design can influence the ability of fluorescently labeled imaging agents to generate tumor contrast and has become an area of significant interest in the field of fluorescence-guided surgery (FGS). Here, we show that the charge-balanced near-infrared fluorescent (NIRF) dye FNIR-Tag enhances the imaging properties of a fluorescently labeled somatostatin analogue. In vitro studies showed that the optimized fluorescent conjugate MMC(FNIR-Tag)-TOC bound primarily via somatostatin receptor subtype-2 (SSTR2), whereas its negatively charged counterpart with IRDye 800CW had higher off-target binding. NIRF imaging in cell line- and patient-derived xenograft models revealed markedly higher tumor contrast with MMC(FNIR-Tag)-TOC, which was attributed to increased tumor specificity. Ex vivo staining of surgical biospecimens from primary and metastatic tumors, as well as involved lymph nodes, demonstrated binding to human tumors. Finally, in an orthotopic tumor model, a simulated clinical workflow highlighted our unique ability to use standard preoperative nuclear imaging for selecting patients likely to benefit from SSTR2-targeted FGS. Our findings demonstrate the translational potential of MMC(FNIR-Tag)-TOC for intraoperative imaging and suggest broad utility for using FNIR-Tag in fluorescent probe development.
Details
- Title: Subtitle
- High-Contrast Detection of Somatostatin Receptor Subtype‑2 for Fluorescence-Guided Surgery
- Creators
- Servando Hernandez Vargas - Brown FoundationSolmaz AghaAmiri - Brown FoundationSukhen C. Ghosh - Brown FoundationMichael P. Luciano - Chemical Biology Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, Maryland21702, United States.Luis C. Borbon - Roy J. and Lucille A. Carver College of MedicinePo Hien Ear - Roy J. and Lucille A. Carver College of MedicineJames R. Howe - Roy J. and Lucille A. Carver College of MedicineJennifer M. Bailey-Lundberg - The University of Texas Health Science CenterGregory D. Simonek - The University of Texas Health Science Center at HoustonDaniel M. Halperin - The University of Texas MD Anderson Cancer CenterHop S. Tran Cao - The University of Texas MD Anderson Cancer CenterNaruhiko Ikoma - The University of Texas MD Anderson Cancer CenterMartin J. Schnermann - Chemical Biology Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, Maryland21702, United States.Ali Azhdarinia - Brown Foundation
- Resource Type
- Journal article
- Publication Details
- Molecular pharmaceutics, Vol.19(11), pp.4241-4253
- DOI
- 10.1021/acs.molpharmaceut.2c00583
- PMID
- 36174110
- PMCID
- PMC9830638
- NLM abbreviation
- Mol Pharm
- ISSN
- 1543-8384
- eISSN
- 1543-8392
- Publisher
- American Chemical Society
- Grant note
- DOI: 10.13039/100000005, name: U.S. Department of Defense, award: BC011506; DOI: 10.13039/100004917, name: Cancer Prevention and Research Institute of Texas, award: RP180812; DOI: 10.13039/100000002, name: National Institutes of Health, award: P50CA174521, U54CA224083
- Language
- English
- Date published
- 11/07/2022
- Academic Unit
- Surgery
- Record Identifier
- 9984322928902771
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