Selective PET Imaging of CXCR4 Using the AlF-labeled Antagonist LY2510924

Overview

Journal Eur J Nucl Med Mol Imaging

Specialties Biophysics
Nuclear Medicine
Radiology

Date 2024 Dec 10

PMID 39658737

Authors

Muriel Aline Spahn

Tom Van Loy

Sofie Celen

Michel Koole

Christophe M Deroose

Christopher Cawthorne

Wim Vanduffel

Dominique Schols

Guy Bormans

Frederik Cleeren

Affiliations

Soon will be listed here.

Abstract

Background: [Ga]PentixaFor detects C-X-C chemokine receptor type 4 (CXCR4) overexpression in various malignancies, such as multiple myeloma and non-Hodgkin lymphomas, as well as in endocrine and inflammatory disorders. This study aimed to develop an AlF-labeled radiotracer derived from LY2510924 for CXCR4-targeted imaging, leveraging the physical and logistical advantages of fluorine-18.

Methods: We designed a CXCR4-specific radioprobe, [F]AlF-NOTA-SC, based on LY2510924 by incorporating a triglutamate linker and NOTA chelator to enable AlF-labeling. The in vitro CXCR4 affinity was assessed using cell-based binding assays. Subsequently, in vivo pharmacokinetics and tumor uptake of [F]AlF-NOTA-SC were assessed in naïve mice and mice with xenografts derived from U87.CD4/U87.CD4.CXCR4 and MM.1 S cells. Finally, biodistribution was determined in a non-human primate using PET-MR.

Results: Compared to Ga-PentixaFor, AlF-NOTA-SC demonstrated similar in vitro affinity for human CXCR4. [F]AlF-NOTA-SC was produced with a decay-corrected radiochemical yield of 21.0 ± 7.1% and an apparent molar activity of 16.4 ± 3.6 GBq/µmol. In [F]AlF-NOTA-SC binding assays on U87.CD4.CXCR4 cells, the total bound fraction was 7.1 ± 0.5% (58% blocking by AMD3100). In naïve mice, the radiotracer did not accumulate in any organs; however, it showed a significant CXCR4-specific uptake in xenografted tumors (SUVmean = 0.04 ± 0.00 (n = 3); SUVmean = 3.04 ± 0.65 (n = 3); SUVmean = 1.95 ± 0.11 (n = 3)). In a non-human primate, [F]AlF-NOTA-SC accumulated in CXCR4 expressing organs, such as the spleen and bone marrow.

Conclusion: [F]AlF-NOTA-SC exhibited CXCR4-specific uptake in vitro and in vivo, with fast and persistent tumor accumulation, making it a strong candidate for clinical translation as an F-alternative to [Ga]PentixaFor.

Citing Articles

Comparing Ga-Pentixafor,F-FDG PET/CT and Chemokine Receptor 4 Immunohistochemistry Staining in Breast Cancer: A Prospective Cross Sectional Study.

Hadebe B, Harry L, Gabela L, Nxasana T, Ndlovu N, Pillay V Cancers (Basel). 2025; 17(5).

PMID: 40075611 PMC: 11898970. DOI: 10.3390/cancers17050763.

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