Stability and immunoreactivity of the monoclonal anticytokeratin antibody TS1 after different degrees of iodination

Citation
A. Johansson et al., Stability and immunoreactivity of the monoclonal anticytokeratin antibody TS1 after different degrees of iodination, ACTA ONCOL, 38(3), 1999, pp. 329-334
Citations number
19
Categorie Soggetti
Onconogenesis & Cancer Research
Journal title
ACTA ONCOLOGICA
ISSN journal
0284186X → ACNP
Volume
38
Issue
3
Year of publication
1999
Pages
329 - 334
Database
ISI
SICI code
0284-186X(1999)38:3<329:SAIOTM>2.0.ZU;2-2
Abstract
The immunoreactivity, stability and in vivo kinetics of an anticytokeratin 8 monoclonal antibody, TSI, were investigated following different degrees o f labeling with I-125 (0.2, 1 and 2-3 I-125/TSI MAb). By testing with ELISA , it was demonstrated that a high degree of iodination, i.e. >2 I-125/TS1, caused a rapid decrease in immunoreactivity to almost zero within 10 days. Furthermore, a complete degradation to low molecular weight fragments and f ree iodine was seen, as shown by SDS PAGE and autoradiography. The differen tly 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 t he differently labeled MAbs were determined. Despite the in vitro instabili ty of the highest iodinated radionuclide conjugate, it was possible to deli ver high doses to the tumors if the conjugate was injected into the animal immediately after competition 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 tissu e dose ratios. There is room for significant improvements in efficacy at ra dioimmunotherapy, which can be gained by optimizing the degree of iodinatio n. For therapeutical applications a high degree of iodination may be an adv antage.