Synthesis and in vivo evaluation of 18F-desbromo-DuP-697 as a PET tracer for cyclooxygenase-2 expression.
Cyclooxygenase-2 (COX-2) overexpression has been observed in various pathologies, such as inflammation, cancer, ischemia, and Alzheimer's disease. As an initial step toward a noninvasive PET technique to assay COX-2 expression, this study describes the synthesis and preliminary evaluation of the radiolabeled COX-2 inhibitor (18)F-desbromo-DuP-697.


METHODS
Desbromo-DuP-697 was radiolabeled by a nucleophilic aromatic substitution reaction of the nitro precursor with (18)F-fluoride. Biodistribution studies of the tracer were performed in a carrageenan-induced hyperalgesia rat model. Brain uptake was investigated with autoradiography. To confirm the results of the biodistribution, COX activity was determined by a peroxidase assay.


RESULTS
Biodistribution studies showed specific binding of the tracer to COX-2 in heart, kidney, brain, and blood cells, but not in the inflamed paw, which was probably due to low COX-2 expression. In the brain, regional differences in tracer uptake were observed, with high uptake in cortical regions. (18)F-Desbromo-DuP-697 did not show any binding to COX-1. Nonspecific uptake was high in fat and intestines.


CONCLUSIONS
Because of its ability to cross the blood-brain barrier, (18)F-desbromo-DuP-697 appears to be suitable for COX-2 imaging in the brain. Its high nonspecific uptake in the intestines may limit its use for imaging in the abdominal region.
de Vries
Erik F J
EF
PET Center, Groningen University Hospital, Groningen, The Netherlands. e.f.j.de.vries@pet.azg.nl
van Waarde
Aren
A
Buursma
Anne Rixt
AR
Vaalburg
Willem
W
D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism*; D051546:Cyclooxygenase 2; D005462:Fluorine Radioisotopes / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D006930:Hyperalgesia / Q000000981:diagnostic imaging* / Q000378:metabolism*; D007527:Isoenzymes / Q000096:biosynthesis*; D007553:Isotope Labeling / Q000379:methods*; D008297:Male; D009928:Organ Specificity; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis*; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D013876:Thiophenes / Q000138:chemical synthesis / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D014018:Tissue Distribution
C479805:18F-2-(4-fluorophenyl)-3-(4-methylsulfonylphenyl)thiophene; D005462:Fluorine Radioisotopes; D007527:Isoenzymes; D019275:Radiopharmaceuticals; D013876:Thiophenes; C064874:DuP 697; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases