Analysis of Br-76-BrdU in DNA of brain tumors after a PET study does not support its use as a proliferation marker

Br-76-bromodeoxyuridine has previously been suggested as a PET tracer to ch aracterize proliferation potential. However, in animal studies a large frac tion of the tissue radioactivity is due to Br-76-bromide, which remains ext racellular for extensive periods and contributes significantly to the level of radioactivity. The present project aimed at investigating whether in hu man brain tumors, sufficient amounts of Br-76-bromodeoxyuridine would be in corporated into DNA, to motivate further attempts with this tracer. Eight p atients with brain tumors: 3 meningiomas, 2 astrocytoma grade IV, 1 astrocy toma olicodendroglioma grade II-IV and 2 metastases, were examined with PET and Br-76-BrdU on three occasions: immediately after injection of the trac er, at 4-6, and at 18-20 hours after administration. After the first PET st udy, diuresis was introduced and maintained for about 12 hours. About 20 ho urs after tracer administration, 200 mg/m(2) bromodeoxyuridine was administ ered to 7 patients median 5.8 (range 1-22) hours prior to operation allowin g the immunohistochemical analysis of the proliferation potential. During t he operation, tumor samples were taken and radioactivity in DNA extracted a nd measured. The uptake of radioactivity was higher in the tumors than in b rain parenchyma. However, in the operative samples only 1-27% (average: 9%) of the radioactivity was found in the DNA fraction. The plasma radioactivi ty remained high throughout the study with only minimal signs of eliminatio n by the diuresis. Br-76-BrdU is extensively metabolized to Br-76-bromide, and only a minor fraction of the radioactivity is found in the DNA fraction , making it unlikely that this tracer can be used for assessment of prolife ration potential. (C) 2001 Elsevier Science Inc. All rights reserved.