title: Systemic perfusion: a method of enhancing relative tumor uptake of radiolabeled monoclonal antibodies.
abstract: We evaluated the feasibility of systemic vascular perfusion with saline (mimicking plasmapheresis) as a method to enhance tumor-specific monoclonal antibody (MoAb) tumor/background ratios. Initially, groups of rats were injected intravenously (i.v.) with 131I-5G6.4 MoAb (murine IgG2aK reactive with ovarian carcinoma). These animal's radioactivity levels were determined by dose calibrator and they were imaged before and after perfusion which was conducted at 4 or 24 h post-antibody injection. Animals were sacrificed after perfusion, as were controls, and normal organ radioactivity levels determined. In addition, nude mice bearing HTB77 ovarian cancers subcutaneously were injected i.v. with 131I-5G6.4 MoAb and were imaged before and after systemic perfusion with saline 24 h post-5G6.4 injection. Perfusion in rats dropped whole-body 5G6.4 levels significantly at both perfusion times (P less than 0.0005). The drop in whole-body radioactivity with perfusion was significantly greater for the animals perfused at 4 h post i.v. 5G6.4 antibody injection (48.3 +/- 5.1%) than for those perfused at 24 h post i.v. antibody injection (32.9 +/- 2.9%) (P less than 0.025). In the nude mice with ovarian cancer xenografts, gamma camera images of tumors were visually and quantitatively (by computer image analysis) enhanced by perfusion, with a 2.33-fold greater decline in whole body uptake than in the tumor (P less than 0.05). These studies show that (1) much background antibody radioactivity can be removed using whole-body perfusion with saline, (2) that the decline in whole body activity is larger with 4 than 24 h perfusion and (3) tumor imaging can be enhanced by this approach.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor 48109-0028.
authors.forename: R L
authors.initials: RL
authors.lastname: Wahl
authors.forename: C R
authors.initials: CR
authors.lastname: Piko
authors.forename: B A
authors.initials: BA
authors.lastname: Beers
authors.forename: O
authors.initials: O
authors.lastname: Geatti
authors.forename: J
authors.initials: J
authors.lastname: Johnson
authors.forename: P
authors.initials: P
authors.lastname: Sherman
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal; D005260:Female; D006801:Humans; D007457:Iodine Radioisotopes; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010051:Ovarian Neoplasms / Q000000981:diagnostic imaging*; D010477:Perfusion; D011877:Radionuclide Imaging; D051381:Rats; D011919:Rats, Inbred Strains; D014018:Tissue Distribution; D014183:Transplantation, Heterologous
chemical_list: D000911:Antibodies, Monoclonal; D007457:Iodine Radioisotopes