18F-CPFPX PET identifies changes in cerebral A1 adenosine receptor density caused by glioma invasion.

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. 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. 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. 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.