PET imaging with zirconium-89 labeled antibodies to guide cancer therapy

PhD ceremony: Mr. T.H. Oude Munnink, 14.30 uur, Aula Academiegebouw, Broerstraat 5, Groningen

Dissertation: PET imaging with zirconium-89 labeled antibodies to guide cancer therapy

Promotor(s): prof. E.G.E. de Vries, prof. R.A.J.O. Dierckx

Faculty: Medical Sciences

The development of antitumor agents that target specific dysregulated processes in tumors is expanding rapidly. One class of these new drugs are antibodies. Development and implementation of new antitumor drugs might be optimized by successful identification, prior to therapy, of the patients that may benefit of a particular drug. Molecular imaging, for example with PET scans, might well contribute in this respect. This thesis aimed at the development and evaluation of PET imaging with radiolabeled antibodies. Antibodies targeted at three relevant proteins were radiolabeled with zirconium-89: human epidermal growth factor receptor-2 (HER2), vascular endothelial growth factor (VEGF) and transforming growth factor-β (TGF-β). PET scans were made to measure the molecular effects of the new antitumor drugs and to explore their pharmacokinetics, organ distribution and tumor uptake. In preclinical studies we showed that this technique was able to detect molecular changes in tumors already one week after treatment. In addition we performed HER2-PET imaging in metastatic breast cancer patients. This revealed new properties of the used antibody (trastuzumab), such as uptake in brain metastases. This thesis is an example of the possible applications of molecular imaging with antibodies during cancer drug development. Currently, this technique is used in the development of several new antitumor drugs, both in preclinical studies as well as in clinical studies.