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Tumor targeting potential of the monoclonal antibody BC‐1 against oncofetal fibronectin in nude mice bearing human tumor implants
Author(s) -
Mariani Giuliano,
Lasku Arben,
Balza Enrica,
Gaggero Barbara,
Motta Cinzia,
Luca Lorella Di,
Dorcaratto Alessandra,
Viale Giuseppe A.,
Neri Dario,
Zardi Luciano
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+<2378::aid-cncr7>3.0.co;2-7
Subject(s) - monoclonal antibody , medicine , oncofetal antigen , cancer research , antibody , immunology , pathology , tumor associated antigen
BACKGROUND The immunoglobulin G 1 (IgG 1 ) 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 125 I‐labeled MoAb BC‐1 in nude mice bearing subcutaneous human tumor implants of U87MG high‐grade astrocytoma and SKMel28 melanoma. 125 I‐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 125 I‐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 125 I‐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 125 I‐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. Cancer 1997; 80:2378‐84. © 1997 American Cancer Society.