title: Thiolations, 99mTc labelings, and animal in vivo biodistributions of divalent monoclonal antibody fragments.
abstract: A number of divalent monoclonal antibody fragments have been derivatized with a bifunctional reagent containing a latent thiol group, and the conjugates were thiol-deprotected by exposure to aqueous hydroxylamine. This two-step procedure enabled convenient 99mTc labeling of thiolated MAb divalent fragments, using either performed 99mTc-glucoheptonate or [99mTc] pertechnetate and single-vial lyophilized formulations of the conjugate and tin. Nonspecific incorporation of radiolabel was negligible, if any, when using nonthiolated antibodies. In animal biodistributions, in nude mice bearing LS174T human colon carcinoma xenografts, the 99mTc-labeled MAb divalent fragments studied were found to result in a 3-fold reduction in the kidney uptake of radioactivity at 24 h, compared to a 99mTc-Fab, and also to lead to improvements in other tumor:nontumor ratios.
authors.affiliation: Immunomedics, Inc., Morris Plains, New Jersey 07950, USA.
authors.forename: S V
authors.initials: SV
authors.lastname: Govindan
authors.forename: D M
authors.initials: DM
authors.lastname: Goldenberg
authors.forename: R C
authors.initials: RC
authors.lastname: Grebenau
authors.forename: H J
authors.initials: HJ
authors.lastname: Hansen
authors.forename: G L
authors.initials: GL
authors.lastname: Griffiths
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*; D002277:Carcinoma / Q000473:pathology; D002851:Chromatography, High Pressure Liquid; D003110:Colonic Neoplasms / Q000473:pathology; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D006801:Humans; D019811:Hydroxylamine; D006898:Hydroxylamines / Q000737:chemistry; D007140:Immunoglobulin Fab Fragments / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*; D007128:Immunoglobulin Fragments / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D015609:Organotechnetium Compounds; D013670:Sodium Pertechnetate Tc 99m; D013056:Spectrophotometry, Ultraviolet; D013400:Sugar Acids; D013439:Sulfhydryl Reagents / Q000737:chemistry; D013997:Time Factors; D014018:Tissue Distribution; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
chemical_list: D000911:Antibodies, Monoclonal; D006898:Hydroxylamines; D007140:Immunoglobulin Fab Fragments; D007128:Immunoglobulin Fragments; D015609:Organotechnetium Compounds; D013400:Sugar Acids; D013439:Sulfhydryl Reagents; D019811:Hydroxylamine; D013670:Sodium Pertechnetate Tc 99m; C100014:technetium Tc 99m gluceptate