PhD ceremony Mr. A.G.T. Terwisscha van Scheltinga: Molecular imaging of tumor characteristics to support targeted cancer therapies. A preclinical focus on HER2, HER3, c-Met, IGF-1R and VEGF-A imaging

PhD ceremony: Mr. A.G.T. Terwisscha van Scheltinga, 14.30 uur, Academiegebouw, Broerstraat 5, Groningen

Dissertation: Molecular imaging of tumor characteristics to support targeted cancer therapies. A preclinical focus on HER2, HER3, c-Met, IGF-1R and VEGF-A imaging

Promotor(s): prof. E.G.E. de Vries, prof. J.G.W. Kosterink

Faculty: Medical Sciences

Tumor cell biology research has resulted in novel molecular targets for anticancer treatment and the development of targeted anticancer drugs. Molecular imaging using antibodies can identify noninvasively the presence of specific targets for the drugs. Moreover, it provides whole body information about tumor uptake and organ distribution of the antibodies. Besides visualization of drug distribution, these antibodies can be used to monitor tumor status during treatment effects, thereby using the receptor or ligands as biomarker. This thesis aimed at the development and preclinical application of new tracers for molecular imaging with 89Zr-labeled radiopharmaceuticals for PET imaging and fluorescent labeled antibodies for optical imaging.

The molecular characteristics which are visualized in this thesis are receptors of growth factors HER2, HER3, c-Met and IGF-1R which are often overexpressed by tumor cells. Also the pro-angiogenic growth factor ligand VEGF-A, which is often abundantly present in the microenvironment, has been used a target for tracers. The drugs acting on these targets are radioactively labeled with zirconium-89 or made fluorescent with IRDye 800CW. With 89Zr-PET the organ distribution and specific tumor uptake of new drugs targeting HER3 or c-Met was visualized. The role of fluorescent imaging in local detection of tumors, for instance during intra-operative imaging has been analyzed. It became clear that near-infrared fluorescent labeled antibodies, targeting VEGF-A or HER2, can be used to detect a tumor. The preclinical findings as described in this thesis are currently under evaluation in clinical trials.