English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Background  The chemokine receptor 4 (CXCR4) is an important molecular target for both visualization and therapy of tumors. The aim of the present study was the synthesis and preclinical evaluation of a  64 Cu-labeled, CXCR4-targeting peptide for positron emission tomography (PET) imaging of CXCR4 expression in vivo.    Methods  For this purpose, 1,4,7-triazacyclononane,1-glutaric acid-4,7-acetic acid (NODAGA), or 1,4,7-triazacyclononane-triacetic acid (NOTA) was conjugated to the highly affine CXCR4-targeting pentixather scaffold. Affinities were determined using Jurkat T-lymphocytes in competitive binding assays employing [ 125 I]FC131 as the radioligand. Internalization and efflux studies of [ 64 Cu]NOTA-pentixather were performed in chem-1 cells, stably transfected with hCXCR4. The stability of the tracer was evaluated in vitro and in vivo .  Small-animal PET and biodistribution studies at different time points were performed in Daudi lymphoma-bearing severe combined immunodeficiency (SCID) mice.    Results  [ 64 Cu]NOTA-pentixather was rapidly radiolabeled at 60 °C with high radiochemical yields ≥90% and purities >99%. [ 64 Cu]NOTA-pentixather offered the highest affinity of the evaluated peptides in this study (IC 50  = 14.9 ± 2.1 nM), showed efficient CXCR4-targeting in vitro and was stable in blood and urine with high resistance to transchelation in ethylenediaminetetraacetic acid (EDTA) challenge studies. Due to the enhanced lipophilicity of [ 64 Cu]NOTA-pentixather (logP = -1.2), biodistribution studies showed some nonspecific accumulation in the liver and intestines. However, tumor accumulation (13.1 ± 1.5% ID/g, 1.5 h p.i.) was CXCR4-specific and higher than in all other organs and resulted in high resolution delineation of Daudi tumors in PET/CT images in vivo.    Conclusions  [ 64 Cu]NOTA-pentixather was fast and efficiently radiolabeled, showed effective CXCR4-targeting, high stability in vitro and in vivo and resulted in high resolution PET/CT images accompanied with a suitable biodistribution profile, making [ 64 Cu]NOTA-pentixather a promising tracer for future application in humans.

[64Cu]NOTA-pentixather enables high resolution PET imaging of CXCR4 expression in a preclinical lymphoma model