title: Radioimmunolocalization and selective delivery of radiation in a rat model system: comparison of intact and fragmented antibody.
abstract: Monoclonal antibody (MoAb) fragments are known to have advantages over intact immunoglobulins for radioimmunoscintigraphy. It is less clear whether they are as effective in the delivery of radioimmunotherapy. The imaging and dosimetric properties of an intact MoAb, K-1-21, reactive against human kappa light chains (LC) were compared with that of its F(ab')2 and Fab fragments using a normal rat model system. Two days after injection of 131I-K-1-21 into rats bearing antigen-sepharose implants, gamma camera images showed specific localization of the MoAb to the target (kappa LC) but not to the control (lambda LC) implant. Better images were obtained with K-1-21 F(ab')2 than with Fab or intact antibody. Mean kappa implant: blood ratios were 8.6 +/- 3.9 for Fab, 7.9 +/- 1.8 for F(ab')2 and 2.0 +/- 0.3 for intact K-1-21. The improvement associated with the use of 131I-K-1-21 fragments was, however, achieved at the expense of lower absolute values of activity at the target site. Thus the absorbed dose delivered to the implant by the intact K-1-21 was double that delivered with F(ab')2 and six times that delivered with Fab. As intact K-1-21 also delivered a greater radiation dose to normal tissues, F(ab')2 fragments may have the greatest overall advantages for therapy with radionuclide MoAb conjugates.
authors.affiliation: Clinical Immunology Research Centre, University of Sydney, NSW, Australia.
authors.forename: K Z
authors.initials: KZ
authors.lastname: Walker
authors.forename: K
authors.initials: K
authors.lastname: Seymour-Munn
authors.forename: J E
authors.initials: JE
authors.lastname: Towson
authors.forename: S M
authors.initials: SM
authors.lastname: Axiak
authors.forename: R L
authors.initials: RL
authors.lastname: Raison
authors.forename: G J
authors.initials: GJ
authors.lastname: Bautovitch
authors.forename: J
authors.initials: J
authors.lastname: Morris
authors.forename: A
authors.initials: A
authors.lastname: Basten
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal; D005260:Female; D007140:Immunoglobulin Fab Fragments; D007128:Immunoglobulin Fragments; D007167:Immunotherapy / Q000379:methods*; D007457:Iodine Radioisotopes; D008297:Male; D011877:Radionuclide Imaging / Q000379:methods*; D011878:Radiotherapy / Q000379:methods*; D051381:Rats; D011916:Rats, Inbred F344; D014018:Tissue Distribution
chemical_list: D000911:Antibodies, Monoclonal; D007140:Immunoglobulin Fab Fragments; D007128:Immunoglobulin Fragments; D007457:Iodine Radioisotopes