In Vivo Evaluation of Indium-111-Labeled 800CW as a Necrosis-Avid Contrast Agent.

Details

Ressource 1Download: 32514888_BIB_CF4B3594ECD7.pdf (1256.09 [Ko])
State: Public
Version: Final published version
License: CC BY 4.0
Serval ID
serval:BIB_CF4B3594ECD7
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
In Vivo Evaluation of Indium-111-Labeled 800CW as a Necrosis-Avid Contrast Agent.
Journal
Molecular imaging and biology
Author(s)
Stroet MCM, de Blois E., Stuurman D.C., de Ridder CMA, Haeck J., Seimbille Y., Mezzanotte L., de Jong M., Löwik CWGM, Panth K.M.
ISSN
1860-2002 (Electronic)
ISSN-L
1536-1632
Publication state
Published
Issued date
10/2020
Peer-reviewed
Oui
Volume
22
Number
5
Pages
1333-1341
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
Current clinical measurements for tumor treatment efficiency rely often on changes in tumor volume measured as shrinkage by CT or MRI, which become apparent after multiple lines of treatment and pose a physical and psychological burden on the patient. Detection of therapy-induced cell death in the tumor can be a fast measure for treatment efficiency. However, there are no reliable clinical tools for detection of tumor necrosis. Previously, we studied the necrosis avidity of cyanine-based fluorescent dyes, which suffered long circulation times before tumor necrosis could be imaged due to low hydrophilicity. We now present the application of radiolabeled 800CW, a commercially available cyanine with high hydrophilicity, to image tumor necrosis in a mouse model.
We conjugated 800CW to DOTA via a PEG linker, for labeling with single-photon emission-computed tomography isotope indium-111, yielding [ <sup>111</sup> In]In-DOTA-PEG <sub>4</sub> -800CW. We then investigated specific [ <sup>111</sup> In]In-DOTA-PEG <sub>4</sub> -800CW uptake by dead cells in vitro, using both fluorescence and radioactivity as detection modalities. Finally, we investigated [ <sup>111</sup> In]In-DOTA-PEG <sub>4</sub> -800CW uptake into necrotic tumor regions of a 4T1 breast tumor model in mice.
We successfully prepared a precursor and developed a reliable procedure for labeling 800CW with indium-111. We detected specific [ <sup>111</sup> In]In-DOTA-PEG <sub>4</sub> -800CW uptake by dead cells, using both fluorescence and radioactivity. Albeit with a tumor uptake of only 0.37%ID/g at 6 h post injection, we were able to image tumor necrosis with a tumor to background ratio of 7:4. Fluorescence and radioactivity in cryosections from the dissected tumors were colocalized with tumor necrosis, confirmed by TUNEL staining.
[ <sup>111</sup> In]In-DOTA-PEG <sub>4</sub> -800CW can be used to image tumor necrosis in vitro and in vivo. Further research will elucidate the application of [ <sup>111</sup> In]In-DOTA-PEG <sub>4</sub> -800CW or other radiolabeled hydrophilic cyanines for the detection of necrosis caused by chemotherapy or other anti-cancer therapies. This can provide valuable prognostic information in treatment of solid tumors.
Keywords
Cell death, Cyanine dyes, Necrosis-avid contrast agents, SPECT, Tumor necrosis
Pubmed
Web of science
Open Access
Yes
Create date
10/06/2020 14:47
Last modification date
15/01/2021 7:11
Usage data