Synthesis and preclinical evaluation of [ 18 F]AlF-NODA-MP-C6-CTHRSSVVC as a PET tracer for CD163-positive tumor-infiltrating macrophages.

Autor: Fernandes B; Dept. of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands; Graduate Program in Biomedical Gerontology, Pontifical Catholic University of Rio Grande do Sul (PUCRS), Porto Alegre, Brazil., Antunes IF; Dept. of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands., Prasad K; Dept. of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands., Vazquez-Matias DA; Dept. of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands., De Mattos EP; Dept. of Biomedical Sciences of Cells & Systems, Section Molecular Cell Biology, University of Groningen, Groningen, the Netherlands., Szymanski W; Department of Radiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands., Jeckel CMM; Graduate Program in Biomedical Gerontology, Pontifical Catholic University of Rio Grande do Sul (PUCRS), Porto Alegre, Brazil., de Vries EFJ; Dept. of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands., Elsinga PH; Dept. of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands. Electronic address: p.h.elsinga@umcg.nl.
Jazyk: angličtina
Zdroj: Nuclear medicine and biology [Nucl Med Biol] 2024 Aug 10; Vol. 138-139, pp. 108946. Date of Electronic Publication: 2024 Aug 10.
DOI: 10.1016/j.nucmedbio.2024.108946
Abstrakt: Positron emission tomography (PET) can provide information about tumor-associated macrophage (TAM) infiltration, as long as a suitable tracer is available. This study aimed to evaluate the radiolabeled peptide [ 18 F]AlF-NODA-MP-C6-CTHRSSVVC as a potential PET tracer for imaging of the CD163 receptor, which is expressed on M2-type tumor-associated macrophages. The conjugated peptide NODA-MP-C6-CTHRSSVVC was labeled with aluminum [ 18 F]fluoride. Tracer binding and its biodistribution were evaluated in an in vitro binding assay and in healthy BALB/c mice, respectively. In addition, different treatments with cyclophosphamide in tumor-bearing mice were used to assess whether the tracer could detect differences in CD163 expression caused by differential TAM infiltration. After 7 days of treatment, animals were injected with [ 18 F]AlF-NODA-MP-C6-CTHRSSVVC, and a 60-min dynamic PET scan was performed, followed by an ex vivo biodistribution study. [ 18 F]AlF-NODA-MP-C6-CTHRSSVVC was prepared in 23 ± 6 % radiochemical yield and showed approximately 50 % of specific receptor-mediated binding in an in vitro binding assay on human CD163-expressing tissue homogenates. No CD163-mediated binding of [ 18 F]AlF-NODA-MP-C6-CTHRSSVVC was detected by PET under normal physiological conditions in healthy BALB/c mice. On the other hand, CD163-positive xenograft tumors were clearly visualized with PET and a positive correlation was found between CD163 levels and the [ 18 F]AlF-NODA-MP-C6-CTHRSSVVC tumor-to-muscle ratio (TMR) obtained from the PET images (Pearson r = 0.76, p = 0.002). No significant differences in the CD163 protein level and in the tracer uptake between treatment groups were found in the tumors. Taken together, [ 18 F]AlF-NODA-MP-C6-CTHRSSVVC appears a promising candidate PET tracer for M2-type TAM, as it binds specifically to CD163 in vitro and its tumor uptake correlates well with CD163 expression in vivo.
Competing Interests: Declaration of competing interest All authors declare no conflicts of interest or relationships relevant to the contents of this manuscript to disclose.
(Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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