Comparative targeting of human colon-carcinoma multicell spheroids using one- and two-step (bispecific antibody) techniques.
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.
Devys
A
A
Unité 211 INSERM, Institut de Biologie, Nantes, France.
Thedrez
P
P
Gautherot
E
E
Faivre-Chauvet
A
A
Saï-Maurel
C
C
Rouvier
E
E
Auget
J L
JL
Barbet
J
J
Chatal
J F
JF
D018033:Antibodies, Bispecific / Q000493:pharmacokinetics* / Q000627:therapeutic use; D002272:Carcinoembryonic Antigen / Q000276:immunology* / Q000378:metabolism; D003110:Colonic Neoplasms / Q000276:immunology / Q000378:metabolism* / Q000532:radiotherapy; D006207:Half-Life; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000378:metabolism*; D007205:Indium Radioisotopes / Q000493:pharmacokinetics*; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics*; D008855:Microscopy, Electron, Scanning; D016499:Radioimmunotherapy / Q000379:methods*; D018874:Spheroids, Cellular / Q000276:immunology / Q000378:metabolism*; D013696:Temperature; D013997:Time Factors; D014407:Tumor Cells, Cultured
D018033:Antibodies, Bispecific; D002272:Carcinoembryonic Antigen; D007140:Immunoglobulin Fab Fragments; D007205:Indium Radioisotopes; D007457:Iodine Radioisotopes