Low kidney uptake of GLP-1R-targeting, beta cell-specific PET tracer, 18F-labeled [Nle14,Lys40]exendin-4 analog, shows promise for clinical imaging View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2016-12

AUTHORS

Kirsi Mikkola, Cheng-Bin Yim, Paula Lehtiniemi, Saila Kauhanen, Miikka Tarkia, Tuula Tolvanen, Pirjo Nuutila, Olof Solin

ABSTRACT

BACKGROUND: Several radiometal-labeled, exendin-based tracers that target glucagon-like peptide-1 receptors (GLP-1R) have been intensively explored for β cell imaging. The main obstacle has been the high uptake of tracer in the kidneys. This study aimed to develop a novel GLP1-R-specific tracer, with fluorine-18 attached to exendin-4, to label β cells for clinical imaging with PET (positron emission tomography). We hypothesized that this tracer would undergo reduced kidney uptake. 18F-labeled [Nle14,Lys40]exendin-4 analog ([18F]exendin-4) was produced via Cu-catalyzed click chemistry. The biodistribution of [18F]exendin-4 was assessed with ex vivo organ γ-counting and in vivo PET imaging. We also tested the in vivo stability of the radiotracer. The localization of 18F radioactivity in rat and human pancreatic tissue sections was investigated with autoradiography. Receptor specificity was assessed with unlabeled exendin-3. Islet labeling was confirmed with immunohistochemistry. The doses of radiation in humans were estimated based on biodistribution results in rats. RESULTS: [18F]exendin-4 was synthesized with high yield and high specific activity. Results showed specific, sustained [18F]exendin-4 uptake in pancreatic islets. In contrast to previous studies that tested radiometal-labeled exendin-based tracers, we observed rapid renal clearance of [18F]exendin-4. CONCLUSIONS: [18F]exendin-4 showed promise as a tracer for clinical imaging of pancreatic β cells, due to its high specific uptake in native β cells and its concomitant low kidney radioactivity uptake. More... »

PAGES

91

References to SciGraph publications

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1186/s13550-016-0243-2

    DOI

    http://dx.doi.org/10.1186/s13550-016-0243-2

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1013879093

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/27957723


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