Non-invasive assessment of tumour cell proliferation with positron emission tomography and [Br-76]bromodeoxyuridine

In oncology, a number of new potential therapeutic modalities, including ge ne 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 ass essed by the incorporation of thymidine into the DNA of S-phase cells. We r eport the use of the thymidine analogue bromodeoxyuridine (BrUdR) labelled with bromide-76 (Br-76) in positron emission tomography (PET). PET scans us ing [Br-76]BrUdR were performed in seven patients with metastatic melanoma. The in vitro cell proliferation in these metastases (n = 7) was compared w ith immunohistochemically evaluated cell proliferation using anti-bromodeox yuridine and MIB-1 antibodies after excision. Blood samples were taken to a nalyse the kinetics of the radiopharmaceutical. The accumulation of [Br-76] BrUdR in PET correlated significantly with the immunohistochemically assess ment of S-phase and cycling cells. In one patient a clinically unexpected m etastases was found on [Br-76]BrUdR-PET which became evident 4 weeks later. Analysis of blood samples showed a fast disappearance of [Br-76]BrUdR; 30 min after injection free bromide was the main form of radioactivity, result ing in a high background activity. Assessment of cell proliferation using [ Br-76]BrUdR is hampered because of fast debromation and high background act ivity. The results are thus rather the effect of the increased circulation in more rapidly proliferating metastases than incorporation of [Br-76]BrUdR into proliferating cells. (C) 1999 Lippincott Williams & Wilkins.