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Improved PET Imaging of Tumors in Mice Using a Novel 18 F-Folate Conjugate with an Albumin-Binding Entity

Fischer, Cindy ; Groehn, Viola ; Reber, Josefine ; Schibli, Roger ; Ametamey, Simon ; Müller, Cristina

In: Molecular Imaging and Biology, 2013, vol. 15, no. 6, p. 649-654

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    Titre
    • Improved PET Imaging of Tumors in Mice Using a Novel 18 F-Folate Conjugate with an Albumin-Binding Entity
    Auteur
    • Fischer, Cindy. Center for Radiopharmaceutical Sciences of ETH, PSI and USZ, Institute of Pharmaceutical Sciences, ETH Zurich, 8093, Zurich, Switzerland
    • Groehn, Viola. Merck & Cie, 8200, Schaffhausen, Switzerland
    • Reber, Josefine. Center for Radiopharmaceutical Sciences of ETH, PSI and USZ, Paul Scherrer Institute, 5232, Villigen-PSI, Switzerland
    • Schibli, Roger. Center for Radiopharmaceutical Sciences of ETH, PSI and USZ, Institute of Pharmaceutical Sciences, ETH Zurich, 8093, Zurich, Switzerland
    • Ametamey, Simon. Center for Radiopharmaceutical Sciences of ETH, PSI and USZ, Institute of Pharmaceutical Sciences, ETH Zurich, 8093, Zurich, Switzerland
    • Müller, Cristina. Center for Radiopharmaceutical Sciences of ETH, PSI and USZ, Paul Scherrer Institute, 5232, Villigen-PSI, Switzerland
    Type de document
    • Postprint
    Langue
    • Anglais
    Publié dans
    • Molecular Imaging and Biology, 2013, vol. 15, no. 6, p. 649-654. Springer US; http://www.springer-ny.com
    Autre version électronique
    Identifiant OAI-PMH
    • oai:doc.rero.ch:315323
    Summary
    Purpose: The folate receptor (FR) is a promising target for nuclear imaging due to its overexpression in many different cancer types. A drawback of using folate radioconjugates is the high accumulation of radioactivity in the kidneys. Therefore, the aim of this study was to develop a 18 F-labeled folate conjugate with an albumin-binding entity to enhance the blood circulation time and hence improve the tumor-to-kidney ratio. Procedures: The novel 18 F-folate was prepared by conjugation of a 18 F-labeled glucose azide to an alkyne-functionalized folate precursor containing an albumin-binding entity via Cu(I)-catalyzed 1,3-dipolar cycloaddition. The radioconjugate was tested in vitro on FR-positive KB tumor cells and by biodistribution and positron emission tomography (PET) imaging studies using KB tumor-bearing mice. Results: The radiosynthesis of the albumin-binding [18 F]fluorodeoxyglucose-folate ([18 F]3) resulted in a radiochemical yield of 1-2% decay corrected (d.c.) and a radiochemical purity of ≥95%. The specific activity of [18 F]3 ranged from 20 to 50GBq/μmol. In vitro experiments revealed FR-specific binding of [18 F]3 to KB tumor cells. In vivo we found an increasing uptake of [18 F]3 into tumor xenografts over time reaching a value of ∼ 15% injected dose (ID)/g at 4h post-injection (p.i.). Uptake in the kidneys (∼ 13% ID/g; 1h p.i.) was approximately fourfold reduced compared to previously published 18 F-labeled folic acid derivatives. An excellent visualization of tumor xenografts with an unprecedentedly high tumor-to-kidney ratio (∼ 1) was obtained by PET imaging. Conclusions: [18 F]3 showed a favorable accumulation in tumor xenografts compared to the same folate conjugate without albumin-binding properties. Moreover, the increased tumor-to-kidney ratios improved the PET imaging quality significantly, in spite of a somewhat higher background radioactivity which was a consequence of the slower blood clearance of [18 F]3