Details

Autor(en) / Beteiligte

• Mariani, Giuliano
• Lasku, Arben
• Pau, Antonio
• Villa, Giuseppe
• Motta, Cinzia
• Calcagno, Giuseppina
• Taddei, Gioconda Z.
• Castellani, Patrizia
• Syrigos, Kostas
• Dorcaratto, Alessandra
• Epenetos, Agamennon A.
• Zardi, Luciano
• Viale, Giuseppe A.

Titel

A pilot pharmacokinetic and immunoscintigraphic study with the technetium‐99m‐labeled monoclonal antibody BC‐1 directed against oncofetal fibronectin in patients with brain tumors

Ist Teil von

• Cancer, 1997-12, Vol.80 (S12), p.2484-2489

Ort / Verlag

New York: John Wiley & Sons, Inc

Erscheinungsjahr

1997

Quelle

Wiley-Blackwell Journals

Beschreibungen/Notizen

• BACKGROUND Preliminary experiments in an animal model have shown the favorable tumor targeting potential in vivo of radiolabeled BC‐1, an immunoglobulin (Ig)G1 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 (99mTc) 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 99mTc‐BC‐1 and was compared with the nonspecific indicator of blood‐brain barrier disruption, 99mTc‐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 T1/2 values of 2‐4 hours and 28‐33 hours, respectively. 99mTc‐BC‐1 showed very low nonspecific uptake in the bone marrow, liver, and spleen. Planar and SPECT imaging with 99mTc‐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, 99mTc‐DTPA. Tumor uptake of 99mTc‐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 99mTc‐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. MoAb Bc‐1 detects human (B+)‐fibronectin, a novel oncofetal marker of neoangiogenesis associated with tumor growth. This plasma pharmacokinetic and scintigraphic study with 99mTc‐BC‐1 was carried out in patients with malignant brain tumors, characterized by high expression of oncofetal fibronectin. The pattern of tumor uptake of 99mTc‐BC‐1 specifically identified areas of tumor growth and of expression of the antigen demonstrated by immunohistochemistry, regardless of simple blood‐brain barrier disruption. 99mTc‐BC‐1 exhibits diagnostic potentials, particularly in cancers with important neoangiogenesis.