Comparative targeting of human colon-carcinoma multicell spheroids using one- and two-step (bispecific antibody) techniques

Int J Cancer. 1996 Sep 17;67(6):883-91. doi: 10.1002/(SICI)1097-0215(19960917)67:6<883::AID-IJC20>3.0.CO;2-1.


In the perspective of radioimmunotherapy (RIT) of micrometastases, we compared, in multicell spheroids (MS), the uptake and retention kinetics of 125I-F(ab)'2 F6 anti-carcinoembryonic antigen (CEA) monoclonal antibody (MAb), and the affinity enhancement system (AES) using an anti-CEA/anti-DTPA-indium bispecific antibody (BsMAb) and a 125I-labeled di-DTPA-In-tyrosine-lysine bivalent hapten. We used MS of colorectal tumor cell lines expressing CEA strongly (LS 174T), weakly (HT-29) or not at all (HRT-18). Uptake and retention kinetics of 125I-F(ab)'2 F6 and 125I-BsMAb used alone gave similar results. The highest uptake values, obtained with LS 174T MS, were slightly lower with AES than with 125I-F(ab)'2 F6. However, effective retention half-lives were longer for AES than for 125I-F(ab)'2 F6 or for 111In-labeled monovalent hapten after pre-incubation of spheroids with BsMAb. Autoradiography showed the same slow and heterogeneous distribution of 125I-F(ab)'2 F6 and 125I-BsMAb. These results indicate that the 2-step technique is more favorable for RIT: uptake values were approximately the same but uptake kinetics were more rapid, and retention half-life was longer than with the one-step technique.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Bispecific / pharmacokinetics*
  • Antibodies, Bispecific / therapeutic use
  • Carcinoembryonic Antigen / immunology*
  • Carcinoembryonic Antigen / metabolism
  • Colonic Neoplasms / immunology
  • Colonic Neoplasms / metabolism*
  • Colonic Neoplasms / radiotherapy
  • Half-Life
  • Humans
  • Immunoglobulin Fab Fragments / metabolism*
  • Indium Radioisotopes / pharmacokinetics*
  • Iodine Radioisotopes / pharmacokinetics*
  • Microscopy, Electron, Scanning
  • Radioimmunotherapy / methods*
  • Spheroids, Cellular / immunology
  • Spheroids, Cellular / metabolism*
  • Temperature
  • Time Factors
  • Tumor Cells, Cultured


  • Antibodies, Bispecific
  • Carcinoembryonic Antigen
  • Immunoglobulin Fab Fragments
  • Indium Radioisotopes
  • Iodine Radioisotopes