In Vivo Evaluation of Gallium-68-Labeled IRDye800CW as a Necrosis Avid Contrast Agent in Solid Tumors.

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Version: Final published version
License: CC BY 4.0
Serval ID
serval:BIB_475468701436
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
In Vivo Evaluation of Gallium-68-Labeled IRDye800CW as a Necrosis Avid Contrast Agent in Solid Tumors.
Journal
Contrast media & molecular imaging
Author(s)
Stroet MCM, de Blois E., Haeck J., Seimbille Y., Mezzanotte L., de Jong M., Löwik CWGM, Panth K.M.
ISSN
1555-4317 (Electronic)
ISSN-L
1555-4309
Publication state
Published
Issued date
2021
Peer-reviewed
Oui
Volume
2021
Pages
2853522
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
Abstract
Necrosis only occurs in pathological situations and is directly related to disease severity and, therefore, is an important biomarker. Tumor necrosis occurs in most solid tumors due to improperly functioning blood vessels that cannot keep up with the rapid growth, especially in aggressively growing tumors. The amount of necrosis per tumor volume is often correlated to rapid tumor proliferation and can be used as a diagnostic tool. Furthermore, efficient therapy against solid tumors will directly or indirectly lead to necrotic tumor cells, and detection of increased tumor necrosis can be an early marker for therapy efficacy. We propose the application of necrosis avid contrast agents to detect therapy-induced tumor necrosis. Herein, we advance gallium-68-labeled IRDye800CW, a near-infrared fluorescent dye that exhibits excellent necrosis avidity, as a potential PET tracer for in vivo imaging of tumor necrosis. We developed a reliable labeling procedure to prepare [ <sup>68</sup> Ga]Ga-DOTA-PEG <sub>4</sub> -IRDye800CW ([ <sup>68</sup> Ga]Ga-1) with a radiochemical purity of >96% (radio-HPLC). The prominent dead cell binding of fluorescence and radioactivity from [ <sup>68</sup> Ga]Ga-1 was confirmed with dead and alive cultured 4T1-Luc2 cells. [ <sup>68</sup> Ga]Ga-1 was injected in 4T1-Luc2 tumor-bearing mice, and specific fluorescence and PET signal were observed in the spontaneously developing tumor necrosis. The ip injection of D-luciferin enabled simultaneous bioluminescence imaging of the viable tumor regions. Tumor necrosis binding was confirmed ex vivo by colocalization of fluorescence uptake with TUNEL dead cell staining and radioactivity uptake in dichotomized tumors and frozen tumor sections. Our presented study shows that [ <sup>68</sup> Ga]Ga-1 is a promising PET tracer for the detection of tumor necrosis.
Pubmed
Web of science
Open Access
Yes
Create date
24/01/2022 19:33
Last modification date
23/01/2024 8:24
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