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¹⁸F-CPFPX PET Identifies Changes in Cerebral A₁ Adenosine Receptor Density Caused by Glioma Invasion

¹ Institute of Medicine, Research Center Jülich, Jülich, Germany
² C. & O. Vogt Institute for Brain Research, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany
³ Institute of Nuclear Chemistry, Research Center Jülich, Jülich, Germany
⁴ Central Institute for Electronics, Research Center Jülich, Jülich, Germany
⁵ Department of Internal Medicine, University of South Florida, Tampa, Florida

ABSTRACT

Adenosine plays a critical role in both tumor proliferation and the cerebral response to tumor invasion. We used 8-cyclopentyl-3-(3-¹⁸F-fluoropropyl)-1-propylxanthine (¹⁸F-CPFPX) PET to investigate A₁ adenosine receptor (A₁AR) density as a potential indicator of the local cerebral response to glioma invasion. Methods: A₁AR density in F98 glioma–bearing rats was examined by ¹⁸F-CPFPX and ³H-CPFPX using PET, quantitative in vitro and ex vivo double-label receptor autoradiography, and immunohistochemical analyses. Results: For all imaging modalities, A₁AR signal intensity was increased in a zone surrounding experimental tumors (136%–146% that in control tissue) (P < 0.01). Immunostaining identified activated astrocytes as the main origin of peritumoral A₁AR upregulation. The results of a pilot ¹⁸F-CPFPX PET study on a patient with recurrent glioblastoma multiforme confirmed increases in A₁AR density in the immediate vicinity of the tumor. Conclusion: ¹⁸F-CPFPX PET is suitable for the detection of peritumoral changes in A₁AR density. Molecular imaging with ¹⁸F-CPFPX PET may open novel possibilities for gaining experimental and clinical insights into the cerebral response to tumor invasion.

Key Words: brain tumor • A₁ adenosine receptor • tumor invasion • ¹⁸F-CPFPX • molecular imaging

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