Titre
In Vivo Evaluation of Indium-111-Labeled 800CW as a Necrosis-Avid Contrast Agent.
Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Périodique
Auteur(s)
Stroet, MCM
Auteure/Auteur
de Blois, E.
Auteure/Auteur
Stuurman, D.C.
Auteure/Auteur
de Ridder, CMA
Auteure/Auteur
Haeck, J.
Auteure/Auteur
Seimbille, Y.
Auteure/Auteur
Mezzanotte, L.
Auteure/Auteur
de Jong, M.
Auteure/Auteur
Löwik, CWGM
Auteure/Auteur
Panth, K.M.
Auteure/Auteur
Liens vers les personnes
Liens vers les unités
ISSN
1860-2002
Statut éditorial
Publié
Date de publication
2020-10
Volume
22
Numéro
5
Première page
1333
Dernière page/numéro d’article
1341
Peer-reviewed
Oui
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Publication Status: ppublish
Résumé
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.
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.
PID Serval
serval:BIB_CF4B3594ECD7
PMID
Open Access
Oui
Date de création
2020-06-10T13:47:50.224Z
Date de création dans IRIS
2025-05-21T03:39:50Z
Fichier(s)![Vignette d'image]()
En cours de chargement...
Nom
32514888_BIB_CF4B3594ECD7.pdf
Version du manuscrit
published
Licence
https://creativecommons.org/licenses/by/4.0
Taille
1.23 MB
Format
Adobe PDF
PID Serval
serval:BIB_CF4B3594ECD7.P001
URN
urn:nbn:ch:serval-BIB_CF4B3594ECD75
Somme de contrôle
(MD5):ec1a62441e98c85cb6ed4f6fa269232a