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A pilot pharmacokinetic and immunoscintigraphic study with the technetium‐99m‐labeled monoclonal antibody BC‐1 directed against oncofetal fibronectin in patients with brain tumors
Author(s) -
Mariani Giuliano,
Lasku Arben,
Pau Antonio,
Villa Giuseppe,
Motta Cinzia,
Calcagno Giuseppina,
Taddei Gioconda Z.,
Castellani Patrizia,
Syrigos Kostas,
Dorcaratto Alessandra,
Epenetos Agamen A.,
Zardi Luciano,
Viale Giuseppe A.
Publication year - 1997
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/(sici)1097-0142(19971215)80:12+<2484::aid-cncr20>3.0.co;2-7
Subject(s) - medicine , oncofetal antigen , technetium 99m , pharmacokinetics , monoclonal antibody , pathology , in vivo , spleen , antibody , glioma , brain tumor , nuclear medicine , cancer research , immunology , scintigraphy , biology , microbiology and biotechnology , tumor associated antigen
Abstract BACKGROUND Preliminary experiments in an animal model have shown the favorable tumor targeting potential in vivo of radiolabeled BC‐1, an immunoglobulin (Ig)G 1 monoclonal antibody (MoAb) that recognizes the human fibronectin isoform (B + ) containing the ED‐B oncofetal domain. This antigen has extremely restricted distribution in normal adult tissues. Instead, it is highly expressed in fetal and tumor tissues, especially in high grade astrocytomas and malignant gliomas of the brain, in which the process of neoangiogenesis linked to tumor growth is particularly important. METHODS This study was carried out with five patients who had malignant brain tumors (four gliomas and one malignant angioblastic meningioma). The BC‐1 MoAb was labeled with technetium‐99m ( 99m Tc) by MDP transchelation. Planar and single photon emission computed tomography (SPECT) imaging was acquired at 4‐6 and 20 hours after intravenous injection of about 450 MBq/0.2 mg 99m Tc‐BC‐1 and was compared with the nonspecific indicator of blood‐brain barrier disruption, 99m Tc‐diethylenetriamine pentaacetic acid (DTPA). Plasma pharmacokinetic analysis was based on serial blood sampling. All patients underwent potentially curative surgery at the end of the study. RESULTS The plasma clearance curves were biexponential, with average T 1/2 values of 2‐4 hours and 28‐33 hours, respectively. 99m Tc‐BC‐1 showed very low nonspecific uptake in the bone marrow, liver, and spleen. Planar and SPECT imaging with 99m Tc‐BC‐1 visualized brain tumors in all patients, with a pattern of intratumor distribution that specifically identified areas of peripheral tumor growth more accurately than the nonspecific indicator, 99m Tc‐DTPA. Tumor uptake of 99m Tc‐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 99m Tc‐BC‐1 for immunoscintigraphy in cancer patients, at least when neoangiogenesis induced by cancer is particularly important. Cancer 1997; 80:2484‐9. © 1997 American Cancer Society.