title: Analysis of 76Br-BrdU in DNA of brain tumors after a PET study does not support its use as a proliferation marker.
abstract: 76Br-bromodeoxyuridine has previously been suggested as a PET tracer to characterize proliferation potential. However, in animal studies a large fraction of the tissue radioactivity is due to 76Br-bromide, which remains extracellular for extensive periods and contributes significantly to the level of radioactivity. The present project aimed at investigating whether in human brain tumors, sufficient amounts of 76Br-bromodeoxyuridine would be incorporated into DNA, to motivate further attempts with this tracer. Eight patients with brain tumors: 3 meningiomas, 2 astrocytoma grade IV, 1 astrocytoma oligodendroglioma grade II-IV and 2 metastases, were examined with PET and 76Br-BrdU on three occasions: immediately after injection of the tracer, at 4-6, and at 18-20 hours after administration. After the first PET study, diuresis was introduced and maintained for about 12 hours. About 20 hours after tracer administration, 200 mg/m(2) bromodeoxyuridine was administered to 7 patients median 5.8 (range 1-22) hours prior to operation allowing the immunohistochemical analysis of the proliferation potential. During the operation, tumor samples were taken and radioactivity in DNA extracted and measured. The uptake of radioactivity was higher in the tumors than in brain parenchyma. However, in the operative samples only 1-27% (average: 9%) of the radioactivity was found in the DNA fraction. The plasma radioactivity remained high throughout the study with only minimal signs of elimination by the diuresis. 76Br-BrdU is extensively metabolized to 76Br-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 proliferation potential.
authors.affiliation: Department of Neurosurgery, University Hospital, Uppsala, Sweden. olafur.gudjonsson@neurokir.uu.se
authors.forename: O
authors.initials: O
authors.lastname: Gudjonssona
authors.forename: M
authors.initials: M
authors.lastname: Bergström
authors.forename: S
authors.initials: S
authors.lastname: Kristjansson
authors.forename: F
authors.initials: F
authors.lastname: Wu
authors.forename: G
authors.initials: G
authors.lastname: Nyberg
authors.forename: K J
authors.initials: KJ
authors.lastname: Fasth
authors.forename: B
authors.initials: B
authors.lastname: Långström
mesh_terms: D000368:Aged; D001254:Astrocytoma / Q000737:chemistry / Q000000981:diagnostic imaging / Q000378:metabolism*; D001932:Brain Neoplasms / Q000737:chemistry / Q000000981:diagnostic imaging / Q000378:metabolism*; D001967:Bromine Radioisotopes; D001973:Bromodeoxyuridine / Q000032:analysis / Q000097:blood / Q000493:pharmacokinetics*; D004273:DNA, Neoplasm / Q000737:chemistry / Q000378:metabolism*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008579:Meningioma / Q000737:chemistry / Q000000981:diagnostic imaging / Q000378:metabolism*; D008875:Middle Aged; D011838:Radiation-Sensitizing Agents / Q000032:analysis / Q000493:pharmacokinetics*; D014055:Tomography, Emission-Computed
chemical_list: D001967:Bromine Radioisotopes; D004273:DNA, Neoplasm; D011838:Radiation-Sensitizing Agents; D001973:Bromodeoxyuridine