title: Non-invasive assessment of tumour cell proliferation with positron emission tomography and [76Br]bromodeoxyuridine.
abstract: In oncology, a number of new potential therapeutic modalities, including gene targeting, are currently under investigation. To evaluate their response at a preclinical level, a non-invasive method providing information about cell proliferation would be highly valuable. The growth fraction can be assessed by the incorporation of thymidine into the DNA of S-phase cells. We report the use of the thymidine analogue bromodeoxyuridine (BrUdR) labelled with bromide-76 (76Br) in positron emission tomography (PET). PET scans using [76Br]BrUdR were performed in seven patients with metastatic melanoma. The in vitro cell proliferation in these metastases (n = 7) was compared with immunohistochemically evaluated cell proliferation using anti-bromo-deoxyuridine and MIB-1 antibodies after excision. Blood samples were taken to analyse the kinetics of the radiopharmaceutical. The accumulation of [76Br]BrUdR in PET correlated significantly with the immunohistochemically assessment of S-phase and cycling cells. In one patient a clinically unexpected metastases was found on [76Br]BrUdR-PET which became evident 4 weeks later. Analysis of blood samples showed a fast disappearance of [76Br]BrUdR; 30 min after injection free bromide was the main form of radioactivity, resulting in a high background activity. Assessment of cell proliferation using [76Br]BrUdR is hampered because of fast debromation and high background activity. The results are thus rather the effect of the increased circulation in more rapidly proliferating metastases than Incorporation of [76Br]BrUdR into proliferating cells.
authors.affiliation: Department of Dermatology, University Hospital, Zürich, Switzerland.
authors.forename: R
authors.initials: R
authors.lastname: Böni
authors.forename: P
authors.initials: P
authors.lastname: Bläuenstein
authors.forename: R
authors.initials: R
authors.lastname: Dummer
authors.forename: G K
authors.initials: GK
authors.lastname: von Schulthess
authors.forename: P A
authors.initials: PA
authors.lastname: Schubiger
authors.forename: H C
authors.initials: HC
authors.lastname: Steinert
mesh_terms: D000328:Adult; D000368:Aged; D001967:Bromine Radioisotopes; D001973:Bromodeoxyuridine; D002455:Cell Division; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008545:Melanoma / Q000000981:diagnostic imaging* / Q000473:pathology / Q000556:secondary; D008875:Middle Aged; D014055:Tomography, Emission-Computed / Q000379:methods*
chemical_list: D001967:Bromine Radioisotopes; D001973:Bromodeoxyuridine