title: Therapy of rat tracheal carcinoma IC-12 in SCID mice: vascular targeting with [213Bi]-MAb TES-23.
abstract: In previous work, we have demonstrated that vascular targeting of [213Bi], an alpha-emitter, to lung blood vessels could efficiently destroy tumour colonies growing in the lung. In order to expand this approach to treatment of tumours growing in other sites, we employed the monoclonal antibody (MAb) TES-23, which reacts with CD44H, preferentially expressed on new blood vessels in tumours. Biodistribution studies of N-succinimidyl [125I] 3-iodobenzoate (SIB)-radiolabelled MAb TES-23 in ICR-severe combined immunodeficient (SCID) mice bearing subcutaneous (s.c.) and intramuscular (i.m.) IC-12 tumours, demonstrated efficient tumour uptake. At 24 h, accumulation in small tumours was 45%ID/g for s.c. tumours, and 58%ID/g for i.m. tumours and in large tumours it was 25%ID/g for s.c. tumours and 17%ID/g for i.m. tumours. Micro-autoradiography data confirmed that radiolabel accumulated in or near tumour blood vessels. Normal tissues had very low levels of radioactivity. Treatment of mice bearing small IC-12 tumours with [213Bi] MAb TES-23 retarded tumour growth relative to animals treated with cold MAb TES-23. Biodistribution and therapy experiments were also performed in BALB/c mice bearing both s.c. and i.m. syngeneic, lung carcinoma (line 498) tumours. [I(125)] SIB MAb TES-23 accumulated efficiently in both s.c. and i.m. tumours (14%ID/g and 15%ID/g, respectively, at 4 h); however, no therapeutic effect of [213Bi] MAb TES-23 treatment could be demonstrated in this model system. The data demonstrate that the timing of vascularisation of the tumours and the delivery kinetics of MAb relative to the half-life of the therapeutic radionuclide are critical for effective therapy.
authors.affiliation: Life Sciences Division, Oak Ridge National Laboratory, TN 37831-6101, USA. kennelsj@ornl.gov
authors.forename: S J
authors.initials: SJ
authors.lastname: Kennel
authors.forename: T
authors.initials: T
authors.lastname: Lankford
authors.forename: S
authors.initials: S
authors.lastname: Davern
authors.forename: L
authors.initials: L
authors.lastname: Foote
authors.forename: K
authors.initials: K
authors.lastname: Taniguchi
authors.forename: I
authors.initials: I
authors.lastname: Ohizumi
authors.forename: Y
authors.initials: Y
authors.lastname: Tsutsumi
authors.forename: S
authors.initials: S
authors.lastname: Nakagawa
authors.forename: T
authors.initials: T
authors.lastname: Mayumi
authors.forename: S
authors.initials: S
authors.lastname: Mirzadeh
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics; D001345:Autoradiography; D001729:Bismuth / Q000493:pharmacokinetics / Q000627:therapeutic use*; D015153:Blotting, Western; D002455:Cell Division; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D016499:Radioimmunotherapy / Q000379:methods*; D011868:Radioisotopes / Q000493:pharmacokinetics / Q000627:therapeutic use*; D051381:Rats; D014134:Tracheal Neoplasms / Q000098:blood supply / Q000473:pathology / Q000532:radiotherapy*; D014183:Transplantation, Heterologous
chemical_list: D000911:Antibodies, Monoclonal; D011868:Radioisotopes; D001729:Bismuth