Novel Peptide-Based PET Probe for Non-invasive Imaging of C-X-C Chemokine Receptor Type 4 (CXCR4) in Tumors.

Details

Serval ID
serval:BIB_0CCD89795847
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Novel Peptide-Based PET Probe for Non-invasive Imaging of C-X-C Chemokine Receptor Type 4 (CXCR4) in Tumors.
Journal
Journal of medicinal chemistry
Author(s)
Trotta A.M., Aurilio M., D'Alterio C., Ieranò C., Di Martino D., Barbieri A., Luciano A., Gaballo P., Santagata S., Portella L., Tomassi S., Marinelli L., Sementa D., Novellino E., Lastoria S., Scala S., Schottelius M., Di Maro S.
ISSN
1520-4804 (Electronic)
ISSN-L
0022-2623
Publication state
Published
Issued date
25/03/2021
Peer-reviewed
Oui
Volume
64
Number
6
Pages
3449-3461
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
The recently reported CXCR4 antagonist 3 (Ac-Arg-Ala-[DCys-Arg-2Nal-His-Pen]-CO <sub>2</sub> H) was investigated as a molecular scaffold for a CXCR4-targeted positron emission tomography (PET) tracer. Toward this end, 3 was functionalized with 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) and 1,4,7-triazacyclononanetriacetic acid (NOTA). On the basis of convincing affinity data, both tracers, [ <sup>68</sup> Ga]NOTA analogue ([ <sup>68</sup> Ga]-5) and [ <sup>68</sup> Ga]DOTA analogue ([ <sup>68</sup> Ga]-4), were evaluated for PET imaging in "in vivo" models of CHO-hCXCR4 and Daudi lymphoma cells. PET imaging and biodistribution studies revealed higher CXCR4-specific tumor uptake and high tumor/background ratios for the [ <sup>68</sup> Ga]NOTA analogue ([ <sup>68</sup> Ga]-5) than for the [ <sup>68</sup> Ga]DOTA analogue ([ <sup>68</sup> Ga]-4) in both in vivo models. Moreover, [ <sup>68</sup> Ga]-4 and [ <sup>68</sup> Ga]-5 displayed rapid clearance and very low levels of accumulation in all nontarget tissues but the kidney. Although the high tumor/background ratios observed in the mouse xenograft model could partially derive from the hCXCR4 selectivity of [ <sup>68</sup> Ga]-5, our results encourage its translation into a clinical context as a novel peptide-based tracer for imaging of CXCR4-overexpressing tumors.
Pubmed
Web of science
Create date
16/03/2021 9:42
Last modification date
13/10/2021 5:44
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