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Comparative targeting of human colon‐carcinoma multicell spheroids using one‐ and two‐step (bispecific antibody) techniques
Author(s) -
Devys Anne,
Thedrez Philippe,
Gautherot Emmanuel,
FaivreChauvet Alain,
SaïMaurel Catherine,
Rouvier Eric,
Auget JeanLouis,
Barbet Jacques,
Chatal JeanFrançois
Publication year - 1996
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19960917)67:6<883::aid-ijc20>3.0.co;2-1
Subject(s) - radioimmunotherapy , carcinoembryonic antigen , kinetics , hapten , chemistry , monoclonal antibody , microbiology and biotechnology , pretargeting , antigen , antibody , biophysics , biology , medicine , immunology , physics , cancer , quantum mechanics
In the perspective of radioimmunotherapy (RIT) of micrometastases, we compared, in multicell spheroids (MS), the uptake and retention kinetics of 125 I‐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 125 I‐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 125 I‐F(ab)′ 2 F6 and 125 I‐BsMAb used alone gave similar results. The highest uptake values, obtained with LS 174T MS, were slightly lower with AES than with 125 I‐F(ab)′ 2 F6. However, effective retention half‐lives were longer for AES than for 125 I‐F(ab)′ 2 F6 or for 111 In‐labeled monovalent hapten after pre‐incubation of spheroids with BsMAb. Autoradiography showed the same slow and heterogeneous distribution of 125 I‐F(ab)′ 2 F6 and 125 I‐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. © 1996 Wiley‐Liss, Inc.