HUMAN POLYCLONAL IMMUNOGLOBULIN LABELED WITH TC-99M VIA NHS-MAG(3) - A COMPARISON OF RADIOCHEMICAL BEHAVIOR AND BIOLOGICAL EFFICACY WITH OTHER LABELING METHODS

The aim of this study was to evaluate the radiochemical behavior, biol ogical distribution, and localization in infection sites in mice of a human polyclonal immunoglobulin (HIG) labelled with Tc-99m by a novel MAG, labelling method. The resulting [Tc-99m]MAG(3)-HIG was compared w ith [Tc-99m]HIG preparations radiolabelled directly via 2 mercaptoetha nol (2 Me) or stannous ion (Sn) reduction and indirectly via 2-iminoth iolane (2-Im) conjugation, All preparations showed similar UV and radi oactivity HPLC profile to that of native HIG except for 2-Im-HIG, whic h showed aggregates, The stabilities of the label to challenge with cy steine were similar for all the preparations. By nondenaturing SDS-PAG E, all preparations other than MAG(3)-HIG showed evidence of lower mol ecular weight fragments. The tissue distribution 4 and 24 h after intr avenous administration of the four preparations were compared in mice previously administered with an isolate of Staphylococcus aureus in on e thigh. The pharmacokinetics varied among the different preparations, When prepared via 2 Me, Sn, and 2-Im, both blood clearance and urinar y excretion were faster than that of labelled MAG(3)-HIG, The absolute uptake in the infected thigh at 24 h was significantly higher for HIG labelled via MAG(3) and 2 Me vs, the remaining methods. The infected thigh/normal thigh radioactivity ratios were similar at both time poin ts for labelled HIG prepared via 2-Me, 2 Im, and NHS-MAG(3) methods bu t was significantly lower at 24 h for HIG prepared via Sn, The radioac tive HPLC profiles of serum at 4 and 24 h were similar to that of the radiolabelled injectates. Based on these data we conclude that each ra diolabelled HIG preparation studied showed increased localization in i nfectious foci although [Tc-99m]MAG(3)-HIG showed superior radiochemic al and biological characteristics under the conditions of this investi gation. (C) 1998 Elsevier Science Inc.