title: Preparation and in vivo evaluation of an N-(p-[125I]iodophenethyl)maleimide-antibody conjugate.
abstract: Protein sulfhydryl reactive N-(4-[125I]iodophenethyl)maleimide (IPEM, 5) was obtained from N-[4-(tri-n-butylstannyl)phenethyl]maleimide in 59-100% radiochemical yield. Conjugation of 5 to NR-ML-05 Fab, a murine anti-melanoma antibody Fab fragment that had been previously reduced with dithiothreitol (DTT), was effected in an average of 85% yield. Results from in vitro chemical challenges and serum stability studies on the IPEM conjugate of NR-ML-05 Fab (6) indicated a stable covalent attachment of the radioiodine. A biodistribution study of the IPEM conjugate in tumor-bearing athymic nude mice showed lack of significant accumulation of radioiodine in the thyroid and stomach which was an indication of in vivo stability. The observed uptake in tumor was consistent with that obtained for Chloramine-T- or p-iodobenzoate-labeled NR-ML-05 Fab conjugates.
authors.affiliation: NeoRx Corporation, Seattle, Washington 98119.
authors.forename: M D
authors.initials: MD
authors.lastname: Hylarides
authors.forename: D S
authors.initials: DS
authors.lastname: Wilbur
authors.forename: M W
authors.initials: MW
authors.lastname: Reed
authors.forename: S W
authors.initials: SW
authors.lastname: Hadley
authors.forename: J R
authors.initials: JR
authors.lastname: Schroeder
authors.forename: L M
authors.initials: LM
authors.lastname: Grant
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology*; D004229:Dithiothreitol; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism; D007140:Immunoglobulin Fab Fragments; D007457:Iodine Radioisotopes; D007462:Iodobenzenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D007553:Isotope Labeling / Q000379:methods*; D008301:Maleimides / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D008545:Melanoma / Q000276:immunology*; D008546:Melanoma, Experimental / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D013961:Thyroid Gland / Q000378:metabolism; D014018:Tissue Distribution
chemical_list: D000951:Antigens, Neoplasm; D007140:Immunoglobulin Fab Fragments; D007457:Iodine Radioisotopes; D007462:Iodobenzenes; D008301:Maleimides; C074012:N-(4-iodophenethyl)maleimide; D004229:Dithiothreitol