In vitro and in vivo evaluation of structure-stability relationship of 111In- and 67Ga-labeled antibody via 1B4M or C-NOTA chelates

• Published in: Nuclear medicine and biology 1997-04, Vol.24 (3), p.225-230
• Main Authors: Lee, Jaetae, Garmestani, Kayhan, Wu, Chuanchu, Brechbiel, Martin W., Chang, Hye K., Choi, Chang W., Gansow, Otto A., Carrasquillo, Jorge A., Paik, Chang H.
• Format: Article
• Language: English
• Subjects: 111In; 1B4M-Antibody; 67Ga; Animals; Antibodies, Monoclonal - chemistry; Biodistribution; Biological and medical sciences; C-NOTA-Antibody; Chelating Agents - chemistry; Chromatography, Gel; Chromatography, High Pressure Liquid; Contrast media. Radiopharmaceuticals; Drug Stability; Female; Gallium Radioisotopes; Heterocyclic Compounds - chemistry; Immunohistochemistry; Indium Radioisotopes; Isothiocyanates - chemistry; Isotope Labeling; Medical sciences; Mice; Mice, Inbred BALB C; Pentetic Acid - analogs & derivatives; Pentetic Acid - chemistry; Pentetic Acid - metabolism; Pharmacology. Drug treatments; Stability; Tissue Distribution; Whole-Body Counting
• ISSN: 0969-8051; 1872-9614
• DOI: 10.1016/S0969-8051(97)00056-5

2-(p-isothiocyanatobenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid (C-NOTA) or 2-(p-isothiocyanatobenzyl) -6-methyl-diethylenetriamine pentaacetic acid (1B4M) was conjugated to monoclonal antibody T101 (IgG2a), radiolabeled with 111In or 67Ga and then purified through size-exclusion HPLC. 111In 1B4M-T101 and 67Ga C-NOTA-T101 were stable in in vitro serum at 37 °C. In contrast, 111In C-NOTA-T101 and 67Ga 1B4M-T101 were unstable. The biodistribution in normal mice reflected the instability of the metal complex; the less-stable 111In C-NOTA conjugate left less tracer in blood, but more in liver and kidney whereas the less-stable 67Ga 1B4M conjugate left less tracer in blood, but more in bone. The biodistribution data suggest that the difference shown between the 111In and 67Ga conjugates might be mediated by differences in the in vivo chemistry of the metallic ions.