Tumor targeting potential of the monoclonal antibody BC-1 against oncofetal fibronectin in nude mice bearing human tumor implants.
BACKGROUND
The immunoglobulin G1 (IgG1) monoclonal antibody (MoAb) BC-1 detects human oncofetal fibronectin, which has extremely restricted distribution in normal adult tissues and is highly expressed in fetal and tumor tissues.


METHODS
We studied the biodistribution of 125I-labeled MoAb BC-1 in nude mice bearing subcutaneous human tumor implants of U87MG high-grade astrocytoma and SKMel28 melanoma. 125I-BC-1 was injected either intraperitoneally (i.p.) or intravenously (i.v.), and biodistribution was measured up to 144 hours after injection. In animals bearing SKMel28 implants, tumor targeting was also evaluated by in vivo imaging of the whole mouse by using a dedicated device based on transmitted light excitation after i.v. injection of MoAb BC-1 conjugated with the infrared fluorophore, CY7-bis(N-hydroxy-succinimido)-ester.


RESULTS
125I-BC-1 showed favorable uptake in the human tumor implants, reaching a maximum of 5.27 +/- 0.48% ID/g in the U87MG astrocytoma (72 hours after i.p. injection). The highest uptake in the SKMel28 melanoma implants was 3.49 +/- 0.25% ID/g (24 hours after i.v. injection). Microautoradiography of tumor specimens obtained after administration of 125I-BC-1 clearly showed radioactivity uptake within the two tumors replicating the same pattern of distribution as that of the oncofetal fibronectin shown by immunohistochemistry with MoAb BC-1. Nonspecific uptake of 125I-BC-1 in the bone marrow and skeletal muscle was much lower than in the tumors. In vivo imaging with the fluorophore-labeled MoAb clearly visualized the tumor implants 72-120 hours after i.v. injection.


CONCLUSIONS
The experimental results obtained in this study demonstrate the favorable tumor targeting potential in vivo of the radiolabeled MoAb BC-1, a useful marker of neo angiogenesis induced by cancer.
Mariani
G
G
Nuclear Medicine Service, DIMI, University of Genoa, Italy.
Lasku
A
A
Balza
E
E
Gaggero
B
B
Motta
C
C
Di Luca
L
L
Dorcaratto
A
A
Viale
G A
GA
Neri
D
D
Zardi
L
L
D000818:Animals; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000951:Antigens, Neoplasm / Q000032:analysis* / Q000276:immunology; D001345:Autoradiography; D005353:Fibronectins / Q000032:analysis* / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000532:radiotherapy*; D014018:Tissue Distribution; D014183:Transplantation, Heterologous
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D005353:Fibronectins; C031192:oncofetal antigens