title: Kinetics of radioiodinated monoclonal antibodies in the rat. Influence of tumour growth and reticuloendothelial system host modulation.
abstract: This experimental study in rats examines the influence of tumour growth and RES function modulation on the kinetics of iodinated MAb IgG1 C241. The study was designed to investigate unspecific accumulation in liver and blood. C241 is raised against human colon adenocarcinoma COLO 205 and reacts with SiLea tumour-associated antigen, also known as tumour-associated antigen 19-9. In 26 rats, 2 micrograms 125I MAb C241 (lodobead labelling method) was given i.v. Blood, organ and tumour content was measured at 0.5, 24, 72 and 144 h. In 61 rats, 10 micrograms 131I MAb C241 (lodogen labelling method) was given i.v. The rats were divided into a non-tumour and a tumour-bearing group and subjected to RES function modulation with Zymosan stimulation or methyl palmitate depression. A syngeneic nitrosoguanidine-induced colonic carcinoma--mean 11 g--was growing in back subcutaneous tissue and hind leg musculature. Serum content of tumour-associated antigen was not found on IRMA testing and tumour content of SiLea ganglioside antigen was found only on lipid binding phase assay. The half-time in blood of iodinated MAb C241 was three days. In-vivo release of iodine was tested by plasma separation on a gel column. More than 90% of the iodine was in the IgG fraction. The activity distribution was almost in equilibrium after 24 h. A tumour/blood activity concentration ratio of 0.5 and liver/blood ratio of 0.3 remained at 72 h and 144 h. Radionuclide accumulation was equally low in the macrophage-rich liver and the kidneys. Tumour-bearing animals had significantly lower blood content (0.37 versus 0.99% g-1) and liver content (0.09 versus 0.31% g-1) at 144 h than non-tumour-bearing rats. The whole body content at 144 h was also lower (24% versus 35% of administered activity) (p = 0.10). Modulation of RES function had no significant influence on the whole body, blood or liver content of 131I MAb C241 activity in non-tumour-bearing animals. In tumour-bearing animals, RES stimulation with Zymosan increased the whole body, liver and blood content of 131I activity. The two tested methods of iodination gave similar results.
authors.affiliation: Department of Surgery, University of Göteborg, Sahlgrenska Hospital, Sweden.
authors.forename: S B
authors.initials: SB
authors.lastname: Holmberg
authors.forename: L
authors.initials: L
authors.lastname: Hafström
authors.forename: E F
authors.initials: EF
authors.lastname: Aronsson
authors.forename: J
authors.initials: J
authors.lastname: Gretarsdottir
authors.forename: L
authors.initials: L
authors.lastname: Jacobsson
authors.forename: S
authors.initials: S
authors.lastname: Mattsson
authors.forename: L
authors.initials: L
authors.lastname: Lindholm
mesh_terms: D000230:Adenocarcinoma / Q000276:immunology; D000818:Animals; D000911:Antibodies, Monoclonal; D003110:Colonic Neoplasms / Q000276:immunology; D005260:Female; D006801:Humans; D007457:Iodine Radioisotopes / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D008297:Male; D012157:Mononuclear Phagocyte System / Q000502:physiology*; D009374:Neoplasms, Experimental / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D015054:Zymosan / Q000494:pharmacology
chemical_list: D000911:Antibodies, Monoclonal; D007457:Iodine Radioisotopes; D015054:Zymosan