Stability and immunoreactivity of the monoclonal anticytokeratin antibody TS1 after different degrees of iodination.
The immunoreactivity, stability and in vivo kinetics of an anticytokeratin 8 monoclonal antibody, TS1, were investigated following different degrees of labeling with 125I (0.2, 1 and 2-3 125I/TS1 MAb). By testing with ELISA, it was demonstrated that a high degree of iodination, i.e. > 2 125I/TS1, caused a rapid decrease in immunoreactivity to almost zero within 10 days. Furthermore, a complete degradation to low molecular weight fragments and free iodine was seen, as shown by SDS PAGE and autoradiography. The differently labeled radionuclide conjugates were injected into nude mice inoculated with HeLa Hep2 cells and tumor doses (estimated by MIRD formalism), tumor:non-tumor dose ratios, % I.D./gram tissue, Gy/MBq and in vivo kinetics of the differently labeled MAbs were determined. Despite the in vitro instability of the highest iodinated radionuclide conjugate, it was possible to deliver high doses to the tumors if the conjugate was injected into the animal immediately after completion of the iodination procedure. Increases from 1.4 Gy to 15.2 Gy delivered tumor dose were obtained with a tenfold increase in the specific activity, without alterations in the tumor:non-tumor tissue dose ratios. There is room for significant improvements in efficacy at radioimmunotherapy, which can be gained by optimizing the degree of iodination. For therapeutical applications a high degree of iodination may be an advantage.
Johansson
A
A
Department of Immunology, University of Umeå, Sweden. amanda.johansson@climi.umu.se
Sandström
P
P
Ullén
A
A
Erlandsson
A
A
Sundström
B
B
Ahlström
K R
KR
Johansson
L
L
Hietala
S O
SO
Stigbrand
T
T
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D001345:Autoradiography; D004307:Dose-Response Relationship, Radiation; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D006367:HeLa Cells; D006801:Humans; D007457:Iodine Radioisotopes; D007633:Keratins / Q000276:immunology*; D051379:Mice; D008819:Mice, Nude; D016719:Radioimmunodetection
D000911:Antibodies, Monoclonal; D007457:Iodine Radioisotopes; D007633:Keratins