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


CONCLUSIONS
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.
Bauer
Andreas
A
Institute of Medicine, Research Center Jülich, Jülich, Germany. an.bauer@fz-juelich.de
Langen
Karl-Josef
KJ
Bidmon
Hans
H
Holschbach
Marcus H
MH
Weber
Simone
S
Olsson
Ray A
RA
Coenen
Heinz H
HH
Zilles
Karl
K
D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D001932:Brain Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D005910:Glioma / Q000000981:diagnostic imaging* / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009361:Neoplasm Invasiveness / Q000000981:diagnostic imaging*; D049268:Positron-Emission Tomography / Q000379:methods; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D051381:Rats; D011916:Rats, Inbred F344; D043682:Receptor, Adenosine A1 / Q000378:metabolism*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D014018:Tissue Distribution; D014970:Xanthines / Q000493:pharmacokinetics*
C468796:8-cyclopenta-3-(3-fluoropropyl)-1-propylxanthine; D014408:Biomarkers, Tumor; D019275:Radiopharmaceuticals; D043682:Receptor, Adenosine A1; D014970:Xanthines