A bifunctional HBED-derivative for labeling of antibodies with 67Ga, 111In and 59Fe. Comparative biodistribution with 111In-DPTA and 131I-labeled antibodies in mice bearing antibody internalizing and non-internalizing tumors
| Autor: | Jochen Schuhmacher, Wolfgang Maier-Borst, Holger Kalthoff, Harald Hauser, Wolf H. Schmiegel, Siegfried Matzku, Gabor Klivényi, Ronald Matys, William E. Hull |
|---|---|
| Rok vydání: | 1992 |
| Předmět: |
Biodistribution
Magnetic Resonance Spectroscopy medicine.drug_class media_common.quotation_subject Gallium Radioisotopes Monoclonal antibody Immunoscintigraphy Iodine Radioisotopes Mice Pharmacokinetics medicine Animals Chelation Internalization Edetic Acid media_common Iron Radioisotopes biology Chemistry Catabolism Indium Radioisotopes Antibodies Monoclonal General Medicine Neoplasms Experimental Pentetic Acid Molecular biology Isotope Labeling Immunology biology.protein Antibody |
| Zdroj: | International journal of radiation applications and instrumentation. Part B, Nuclear medicine and biology. 19(8) |
| ISSN: | 0883-2897 |
| Popis: | To investigate whether bifunctional ligands containing chelating structures other than EDTA and DTPA and metallic radiotracers other than 111In will reduce the non-specific radioactivity uptake in the liver during immunoscintigraphy, we synthetized an isothiocyanato-substituted phenolic polyaminocarboxylic acid (HBED-CI) for labeling of MAbs with 67Ga, 111In and 59Fe. Biodistribution of HBED-CI-labeled MAbs was compared to that of 131I and 111In-DTPA labeled MAbs in nude mice bearing tumors, which differ with regard to intracellular internalization and catabolism of the corresponding MAb-antigen complex. In the liver a continuous radioactivity excretion for 67Ga-HBED-CI-labeled MAbs was observed with kinetics that parallel 131I clearance after administration of 131I-MAbs, while 111In-HBED-CI-labeling led to a constant 111In liver level quite similar to that of 111In-DTPA-MAbs. In tumors, 67Ga-HBED-CI-MAb uptake again paralleled that of 131I-MAbs, showing continuous accumulation in tumor tissues when internalization of the MAb-antigen complex was not involved. A much lower uptake, which peaked between 24 and 48 h, was found in the case of MAb-antigen internalization. 111In of 111In-HBED-CI- and 111In-DTPA-labeled MAbs continuously accumulated in both types of tumors. Compared with 111In-DTPA-MAbs, an improvement in tumor-to-liver ratios, due to the reduced liver radioactivity associated with 67Ga-HBED-CI-labeled MAbs, could only be obtained with non-internalizing tumors. The time course of radioactivity distribution in the liver and in MAb-internalizing tumors after administration of 67Ga-HBED-CI-, 111In-HBED-CI- and 111In-DTPA-labeled MAbs further indicates a dominating influence of the metallic radiotracer rather than the ligand on retention or excretion of radioactivity in MAb-catabolizing tissues. |
| Databáze: | OpenAIRE |
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