Synthesis of a Fluorescently Labeled 68Ga-DOTA-TOC Analog for Somatostatin Receptor Targeting Academic Article uri icon

Overview

MeSH Major

  • Enzyme Inhibitors
  • Molecular Imaging
  • Single-Cell Analysis

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, (68)Ga-DOTA-TOC, to produce the dual-labeled analog, (68)Ga-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 (68)Ga-MMC(IRDye 800CW)-TOC, along with clearance via the reticuloendothelial system. Higher uptake was observed in most tissues compared to (68)Ga-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 (68)Ga-MMC(IRDye 800CW)-TOC for intraoperative detection of SSTR2-expressing tumors.

publication date

  • July 13, 2017

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC5512127

Digital Object Identifier (DOI)

  • 10.1021/acsmedchemlett.7b00125

PubMed ID

  • 28740605

Additional Document Info

start page

  • 720

end page

  • 725

volume

  • 8

number

  • 7