title: Development and biologic evaluation of a kit for preformed chelate technetium-99m radiolabeling of an antibody Fab fragment using a diamide dimercaptide chelating agent.
abstract: A kit has been developed for 99mTc antibody radiolabeling via defined chemistry using an N2S2 diamide dimercaptide bifunctional chelating agent and the performed chelate method. The process involved efficient transchelation of 99mTc from gluconate to 2,3,5,6-tetrafluorophenyl 4,5-bis-S-(1-ethoxyethyl) mercaptoacetamidopentanoate as an active ester ligand and subsequent conjugation to antibody lysine amine functional groups. The use of the ethoxyethyl group for sulfur protection allowed optimum yields of 99mTc N2S2 chelate formation with complete retention of the active ester. Subsequent addition of antibody Fab fragment gave 99mTc chelate conjugates indistinguishable from the stepwise in situ esterification and purification of the 99mTc N2S2 complex followed by conjugation as previously shown to give stable 99mTc antibody fragments with retained immunoreactivity and tumor-targeting properties.
authors.affiliation: NeoRx Corporation, Seattle, Washington 98119.
authors.forename: S
authors.initials: S
authors.lastname: Kasina
authors.forename: T N
authors.initials: TN
authors.lastname: Rao
authors.forename: A
authors.initials: A
authors.lastname: Srinivasan
authors.forename: J A
authors.initials: JA
authors.lastname: Sanderson
authors.forename: J N
authors.initials: JN
authors.lastname: Fitzner
authors.forename: J M
authors.initials: JM
authors.lastname: Reno
authors.forename: P L
authors.initials: PL
authors.lastname: Beaumier
authors.forename: A R
authors.initials: AR
authors.lastname: Fritzberg
mesh_terms: D000599:Amino Acids, Diamino / Q000138:chemical synthesis / Q000493:pharmacokinetics; D000603:Amino Acids, Sulfur / Q000138:chemical synthesis / Q000493:pharmacokinetics; D000818:Animals; D005069:Evaluation Studies as Topic; D007140:Immunoglobulin Fab Fragments; D007128:Immunoglobulin Fragments; D007553:Isotope Labeling; D051379:Mice; D008819:Mice, Nude; D011933:Reagent Kits, Diagnostic; D013667:Technetium; D014018:Tissue Distribution
chemical_list: D000599:Amino Acids, Diamino; D000603:Amino Acids, Sulfur; D007140:Immunoglobulin Fab Fragments; D007128:Immunoglobulin Fragments; D011933:Reagent Kits, Diagnostic; C069725:2,3,5,6-tetrafluorophenyl 4,5-bis-S-(1-ethoxyethyl)mercaptoacetamidopentanoate; D013667:Technetium