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- Johansson, Amanda, et al.
(författare)
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Stability and immunoreactivity of the monoclonal anticytokeratin antibody TS1 after different degrees of iodination.
- 1999
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Ingår i: Acta Oncologica. - 0284-186X .- 1651-226X. ; 38:3, s. 329-334
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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- Larsson, Anne, et al.
(författare)
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Methods for estimating uptake and absorbed dose in tumours from I-125 labelled monoclonal antibodies, based on scintigraphic imaging of mice.
- 1999
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Ingår i: Acta Oncologica. - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 38:3, s. 361-365
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Tidskriftsartikel (refereegranskat)abstract
- Monoclonal antibodies for radioimmunotargeting are often tested in tumour bearing nude mice. In vivo determination of the uptake of the monoclonal antibody in the tumour requires quantitative scintigraphy, and this in turn requires an adequate method for subtraction of radiation from the normal tissue. For this reason, two different methods for background subtraction were evaluated, a contralateral background region of interest or an irregular one, surrounding the tumour. A pinhole collimator was used for the scintigraphy and the monoclonal antibodies were labelled with 125I. Furthermore, a method was developed for estimation of the mean absorbed dose in the tumour from these repeated quantitative scintigraphic measurements. This requires that the tumour mass can be accurately estimated in vivo. Finally, the results were compared with in vitro measurements of the uptake.
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- Riklund, Katrine, et al.
(författare)
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A putative mechanism for the non-specific uptake of intact radiolabelled monoclonal antibodies in the testes and prostate.
- 1996
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Ingår i: Acta Oncologica. - 0284-186X .- 1651-226X. ; 35:3, s. 303-307
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Tidskriftsartikel (refereegranskat)abstract
- Non-specific testicular accumulation of radiolabelled intact anti-CEA monoclonal antibody (MAb), (A431/26, Behringwerke AG) was observed in 11 out of 12 patients with the testes and prostate included in the examination field at radioimmunoscintigraphy (RIS). Previous studies have shown that placental alkaline phosphatase (PLAP) serves as an Fc-receptor, mediating IgG transport through the placenta. A closely related protein, the germ cell alkaline phosphatase (GCAP), is expressed in the testes. The testicular uptake of IgG is observed only when intact but not fragmented MAbs are used, indicating involvement of Fc-receptors. MDCK cells (dog kidney cell line) transfected with the plasmid pSVT7 containing the GCAP gene were shown to acquire the capacity to both express membrane bound GCAP and to bind IgG on the cell surface. This might indicate that GCAP is responsible for the non-specific accumulation of intact MAb in the testes and prostate often observed when intact murine MAbs are used for radioimmunolocalization (RIL).
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