A pilot pharmacokinetic and immunoscintigraphic study with the technetium-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 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 T(1/2) 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.
Mariani
G
G
Nuclear Medicine Service, DIMI, University of Genoa, Italy.
Lasku
A
A
Pau
A
A
Villa
G
G
Motta
C
C
Calcagno
G
G
Taddei
G Z
GZ
Castellani
P
P
Syrigos
K
K
Dorcaratto
A
A
Epenetos
A A
AA
Zardi
L
L
Viale
G A
GA
D000328:Adult; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics; D000951:Antigens, Neoplasm / Q000032:analysis* / Q000276:immunology; D001932:Brain Neoplasms / Q000000981:diagnostic imaging*; D005260:Female; D005353:Fibronectins / Q000032:analysis* / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011877:Radionuclide Imaging; D013667:Technetium
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D005353:Fibronectins; C031192:oncofetal antigens; D013667:Technetium