Tumour Targeting Using Radiolabelled EGF Conjugates

Tumour targeted radiotherapy is an appealing approach for treatment of disseminated tumour cells. A targeting agent that specifically binds to a structure on tumour cells is then used to transport therapeutically relevant radionuclides. The epidermal growth factor receptor, EGFR, is overexpressed on tumour cells in several malignancies, e.g. highly malignant gliomas. In this thesis, three types of radiolabelled EGF-conjugates, aimed for targeting to EGFR-expressing tumour cells, were developed and studied: EGF-dextran labelled with 125I, EGF labelled with 211At, and two EGF-chelates, DTPA-EGF and Bz-DTPA-EGF, labelled with the radioactive metals 111In and 177Lu.The targeting properties of radioiodinated EGF-dextran were first studied in cultured glioma cells. Radioiodine coupled to the dextran part of EGF-dextran was retained in cells appreciably longer than radioiodine coupled to EGF. This can give about 100 times increased radiation dose to tumour cells…

Contents

Introduction
Background
Gliomas
The EGFR family
Receptors
Ligands
Signalling
Expression in tumours
Tumour targetin
Inhibiting growth factor receptor function
Targeting agents
Radionuclides
Aim
EGF-dextran (paper I and II)
Conjugate
Binding and cellular processing
Signalling studies
Comments
At-EGF and gefitinib (paper III an IV)
Conjugates
Binding and cellular processing
Experimental therapy in vitro
Comments
EGF-chelates (paper V and VI)
Conjugates
Binding and cellular processing
Affinity determination
Stability studie
Animal studies
Comments
Summary and future studies
Summary
Future studies
Acknowledgements
References

Author: Sundberg, ├ůsa

Source: Uppsala University Library

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