[Comparative studies of 111In-labeled monoclonal antibody using spacer-containing and non-spacer bifunctional chelates: (II). Biodistribution, metabolism and excretion in vivo].

Abstract

Indium-111-labeled A7 monoclonal antibodies using two spacer-containing chelates, succinimido-EGS-DTPA (EGS-DTPA: diester spacer) and maleimido-C10-Bz-EDTA (C10-Bz-EDTA: hydrocarbon spacer) were investigated in human LS180 colon tumor bearing nude mice and were compared with two non-spacer chelates, cyclic DTPA dianhydride (cDTPAA) and isothiocyanatobenzyl-EDTA (SCN-Bz-EDTA). Compared with immunoconjugates using non-spacer chelates, immunoconjugates using spacer-containing chelates, especially C10-Bz-EDTA-A7 showed lower 111In activity in normal organs. The radioactivity in the liver for C10-Bz-EDTA-A7 decreased continuously till 96 hrs postinjection, however, this liver radioactivity for EGS-DTPA-A7 showed little change after 24 hrs. Moreover, in liver subcellular distribution study, EGS-DTPA-A7 showed a higher activity retention in mitochondrial fraction which contained lysosome, a place for metabolizing and storing of 111In labeled antibody, than that of C10-Bz-EDTA-A7. The C10-Bz-EDTA-A7 conjugate demonstrated more preferable tumor-to-non tumor contrast on the scintigrams than that found with other three immunoconjugates. Up to 96 hrs postinjection, tumor bearing nude mice injecting with immunoconjugates using spacer-containing chelates excreted twice radioactivity from whole body than that excreted by using non-spacer chelates. Interestingly, different from other three chelates, C10-Bz-EDTA-A7 were mainly excreted via feces. We conclude that the decrease of radioactivity in normal tissues in the case of EGS-DTPA-A7 was duo to the rapid decrease of activity in the blood, while in the case of C10-Bz-EDTA-A7 it was due to the quickly excreted small metabolite through faces. 111In labeled C10-Bz-EDTA conjugate is superior, at least when conjugated with A7, to other three chelate conjugates used in this study.

• Authors: B Sun
• Journal: Kaku igaku. The Japanese journal of nuclear medicine (Kaku Igaku) Vol. 31 Issue 5 Pg. 473-87 (May 1994) ISSN: 0022-7854 [Print] Japan
• PMID: 8028219 (Publication Type: English Abstract, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Chelating Agents
• Indium Radioisotopes
• Pentetic Acid
• Edetic Acid

Topics

• Animals
• Antibodies, Monoclonal (metabolism)
• Chelating Agents (pharmacokinetics)
• Edetic Acid
• Female
• Humans
• Indium Radioisotopes (pharmacokinetics)
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Pentetic Acid
• Radioimmunodetection
• Tissue Distribution