A PILOT PHARMACOKINETIC AND IMMUNOSCINTIGRAPHIC STUDY WITH THE TC-99M-LABELED MONOCLONAL-ANTIBODY BC-1 DIRECTED AGAINST ONCOFETAL FIBRONECTIN IN PATIENTS WITH BRAIN-TUMORS

BACKGROUND. Preliminary experiments in an animal model have shown the favorable tumor targeting potential in vivo of radiolabeled BC-1, an i mmunoglobulin (Ig)GI monoclonal antibody (MoAb) that recognizes the hu man fibronectin isoform (B+) containing the ED-B oncofetal domain, Thi s antigen has extremely restricted distribution in normal adult tissue s. Instead, it is highly expressed in fetal and tumor tissues, especia lly in high grade astrocytomas and malignant gliomas of the brain, in which the process of neoangiogenesis linked to tumor growth is particu larly important. METHODS. This study was carried out with five patient s who had malignant brain tumors (four gliomas and one malignant angio blastic meningioma). The BC-1 MoAb was labeled with technetium-99m (Tc -99m) by MDP transchelation, Planar and single photon emission compute d tomography (SPECT) imaging was acquired at 4-6 and 20 hours after in travenous injection of about 450 MBq/0.2 mg Tc-99m-BC-1 and was compar ed. with the nonspecific indicator of blood-brain barrier disruption, Tc-99m-diethyienetriamine pentaacetic acid (DTPA). Plasma pharmacokine tic analysis was based on serial blood sampling. All patients underwen t potentially curative surgery at the end of the study. RESULTS. The p lasma clearance curves were biexponential, with average T-1/2 values o f 2-4 hours and 28-33 hours, respectively. Tc-99m-BC-1 showed very low nonspecific uptake in the bone marrow, liver, and spleen. Planar and SPECT imaging with Tc-99m-BC-1 visualized brain tumors in all patients , with a pattern of intratumor distribution that specifically identifi ed areas of peripheral tumor growth more accurately than the nonspecif ic indicator, Tc-99m-DTPA. Tumor uptake of Tc-99m-BC-1 was correlated with the expression of the specific oncofetal fibronectin, as shown by immunohistochemistry on surgical samples. CONCLUSIONS. These results indicate the diagnostic potential of MoAb Tc-99m-BC-1 for immunoscinti graphy in cancer patients, at least when neoangiogenesis induced by ca ncer is particularly important. (C) 1997 American Cancer Society.