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
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
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 10:42
Last modification date
13/10/2021 6:44