Evaluation of a new DTPA-derivative chelator: comparative biodistribution and imaging studies of 111In-labeled B3 monoclonal antibody in athymic mice bearing human epidermoid carcinoma xenografts

Nucl Med Biol. 1993 Nov;20(8):955-62. doi: 10.1016/0969-8051(93)90096-d.

Abstract

Biodistribution and imaging characteristics of monoclonal antibody (MAb) B3 conjugated to either the 2-(p-isothiocyanatobenzyl)-cyclohexyl-DTPA (CHX-B) or 2-(p-isothiocyanatobenzyl)-6-methyl-DTPA (1B4M) and labeled with 111In, were evaluated in nude mice bearing A431 human epidermoid carcinoma xenografts. MAb B3, is a murine IgG1k reacting with a carbohydrate antigen abundantly expressed by most carcinomas. Both 111In-(CHX-B)-B3 and 111In-(1B4M)-B3 showed good tumor targeting with peak values observed at 72 h with 27.6 +/- 7.6 and 25.4 +/- 1.7% ID/g, respectively (P > 0.05). High tumor-to-organ ratios were also observed and, confirmed by the imaging results. In particular, tumor-to-liver ratios increased from 5.0 +/- 0.9 at 24 h to 9.2 +/- 2.0 at 168 h for 111In-(CHX-B)-B3 and from 4.5 +/- 0.6 to 8.9 +/- 3.5 for 111In-(1B4M)-B3. This was mainly the result of low liver accumulation of both 111In-(CHX-B)-B3 and 111In-(1B4M)-B3, with only 2.48 +/- 0.46 and 2.5 +/- 0.9% ID/g at 168 h, respectively (P > 0.05). Our findings indicate that either CHX-B or 1B4M can be successfully used for 111In-labeling of MAbs and that 111In-B3 may represent a promising radioimmunoimaging agent.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Antibodies, Monoclonal / metabolism
  • Carcinoma, Squamous Cell / diagnostic imaging*
  • Carcinoma, Squamous Cell / metabolism*
  • Chelating Agents / pharmacokinetics*
  • Drug Stability
  • Female
  • Humans
  • Immunotoxins / metabolism*
  • Indium Radioisotopes*
  • Isothiocyanates / pharmacokinetics*
  • Mice
  • Mice, Nude
  • Neoplasm Transplantation
  • Pentetic Acid / analogs & derivatives*
  • Pentetic Acid / pharmacokinetics
  • Radionuclide Imaging
  • Tissue Distribution
  • Transplantation, Heterologous

Substances

  • Antibodies, Monoclonal
  • Chelating Agents
  • Immunotoxins
  • Indium Radioisotopes
  • Isothiocyanates
  • 2-(4-isothiocyanatobenzyl)-6-methyldiethylenetriaminepentaacetic acid
  • N-(2-amino-3-(4-isothiocyanatophenyl)propyl)cyclohexane-1,2-diamine-N,N',N',N'',N''-pentaacetic acid
  • Pentetic Acid