Synthesis of a fluorescently labeled (68)Ga-DOTA-TOC analog for somatostatin receptor targeting Journal Article
| Authors: | Ghosh, S. C.; Hernandez Vargas, S.; Rodriguez, M.; Kossatz, S.; Voss, J.; Carmon, K. S.; Reiner, T.; Schonbrunn, A.; Azhdarinia, A. |
| Article Title: | Synthesis of a fluorescently labeled (68)Ga-DOTA-TOC analog for somatostatin receptor targeting |
| Abstract: | Fluorescently labeled imaging agents can identify surgical margins in real-time to help achieve complete resections and minimize the likelihood of local recurrence. However, photon attenuation limits fluorescence-based imaging to superficial lesions or lesions that are a few millimeters beneath the tissue surface. Contrast agents that are dual-labeled with a radionuclide and fluorescent dye can overcome this limitation and combine quantitative, whole-body nuclear imaging with intraoperative fluorescence imaging. Using a multimodality chelation (MMC) scaffold, IRDye 800CW was conjugated to the clinically used somatostatin analog, 68Ga-DOTA-TOC, to produce the dual-labeled analog, 68Ga-MMC(IRDye 800CW)-TOC, with high yield and specific activity. In vitro pharmacological assays demonstrated retention of receptor-targeting properties for the dual-labeled compound with robust internalization that was somatostatin receptor (SSTR) 2-mediated. Biodistribution studies in mice identified the kidneys as the primary excretion route for 68Ga-MMC(IRDye 800CW)-TOC, along with clearance via the reticuloendothelial system. Higher uptake was observed in most tissues compared to 68Ga-DOTA-TOC but decreased as a function of time. The combination of excellent specificity for SSTR2-expressing cells and suitable biodistribution indicate potential application of 68Ga-MMC(IRDye 800CW)-TOC for intraoperative detection of SSTR2-expressing tumors. © 2017 American Chemical Society. |
| Keywords: | pet; somatostatin receptor; dual labeling; nirf |
| Journal Title: | ACS Medicinal Chemistry Letters |
| Volume: | 8 |
| Issue: | 7 |
| ISSN: | 1948-5875 |
| Publisher: | American Chemical Society |
| Date Published: | 2017-07-13 |
| Start Page: | 720 |
| End Page: | 725 |
| Language: | English |
| DOI: | 10.1021/acsmedchemlett.7b00125 |
| PROVIDER: | scopus |
| PMCID: | PMC5512127 |
| PUBMED: | 28740605 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 2 August 2017 -- Source: Scopus |
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