Yttrium-90 and Rhenium-188 Radiopharmaceuticals for Radionuclide Therapy

Chapter 5
PRECLINICAL EVALUATION OF
90 Y LABELLED RITUXIMAB AND ERIC-1:
TWO ANTIBODIES FOR TUMOUR THERAPY
K. SCHOMÄCKER, T. FISCHER
Department of Nuclear Medicine,
University of Cologne,
Cologne, Germany
Abstract
The project described in this chapter focuses on harnessing the great potential of
radionuclide therapy, using various vehicles to transport radionuclides into tumour tissues. The
main aim of the project was to make specific vehicle molecules whose tumour affinity and
suitability for radioactive coupling have been proven through laboratory trials on animals and
cell cultures at the Department of Nuclear Medicine, University of Cologne, Germany, and to
label them with 90 Y. The vectors to transport radionuclides into tumour tissue for treatment
were antibodies against lymphomas and neuroblastomas.
Tumour pretargeting has shown clear advantages over the direct application of labelled
antibodies with regard to tumour to background ratios. The pretargeting strategy would be
first evaluated on cell cultures and the results then transferred to in vivo experiments on
tumour bearing mice. Briefly, the first component of a three step pretargeting strategy would
consist of the biotinylated antibody. This would include the protocol for determination of
the number of biotin molecules per antibody. Using this technique, a stock of biotinylated
antibody in lyophilized form can be built up, ready for further experiments. In the second
step, commercially available avidin streptavidin would be used. The third and final step is the
binding of radiolabelled ( 188 Re, 90 Y) biotin to the tumour cells through the avidin antibody
bridge, after administration of a clearing agent.
Initial evaluations of the potential radiopharmaceuticals have been carried out by in
vitro experiments on cell lines expressing the corresponding antigen. The work done so far for
the three step pretargeting method can be summarized as follows:
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Yttrium-90 labelling of biotin DOTA;
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Coupling of biotinylated rituximab to CD20 positive Raji cells;
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Successful labelling of cells conjugated with a complex of biotinylated antibody and
avidin with 90 Y DOTA biotin;
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First animal experiments with the pretargeting method: results are disappointing so far.
Furthermore, new results were achieved with 131 I and 90 Y labelled ERIC1 antibodies
directed against neural cell adhesion molecule (NCAM) positive neuroblastomas. The
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