Combined Peptide Receptor-Targeted Cytotoxic/-Radionuclide Therapy for the Treatment of Metastatic Pheochromocyto­ma

PhD student: Josephine Liers
Supervisor at TUD: Christian G. Ziegler
Supervisor at KCL: Shanta Persaud
Start date: 01.04.2016

Pheochromocytomas and paragangliomas (PPGLs) are catecholamine-secreting neuroendocrine tumors arising from chromaffin cells in the adrenals or at extra adrenal sites, respectively. Whereas most PPGLs are benign, therapeutic options are limited especially for metastatic disease. Therefore, reliable metastasis models are necessary to evaluate novel therapeutic strategies.

Part of my previous work focused on the establishment and characterization of different metastasis mouse models for pheochromocytoma. These investigations have recently been published (Ullrich M, Liers J et al., Strain-specific metastatic phenotypes in pheochromocytoma allograft mice, Endocr Relat Cancer, 2018, 25:993-1004).

Most PPGLs exhibit high densities of somatostatin type 2 receptors (SSTR2). Somatostatin receptors are G-protein coupled receptors that are involved in various metabolic processes including also diabetes. Downstream signalling of these receptors is an interesting drugable target for both cancer and metabolic diseases.

In our group we functionally investigate the tumor´s metabolic niche and theragnostic targets using positron emission tomography (PET) radiotracers such as [¹⁸F]FDG, [¹⁸F]FDOPA and [⁶⁴Cu]Cu-DOTA-TATE. Furthermore, I am currently working on epigenetic up-regulation of SSTR2 expression as combinatorial/-adjuvant therapeutic approach to enhance the outcome of [¹⁷⁷Lu]Lu‑DOTA-TATE endoradiotherapy in PPGLs.

Publications:

Strain-specific metastatic phenotypes in pheochromocytoma allograft mice. M. Ullrich, J. Liers, M. Peitzsch, A. Feldmann, R. Bergmann, U. Sommer, S. Richter, S.R. Bornstein, M. Bachmann, G. Eisenhofer, C.G. Ziegler, J. Pietzsch. Endocr Relat Cancer. 2018;25:993-1004.

Fluorescent mouse pheochromocytoma spheroids expressing hypoxia-inducible factor 2 alpha: Morphologic and radiopharmacologic characterization. V. Seifert, J. Liers, T. Kniess, S. Richter, N. Bechmann, A. Feldmann, M. Bachmann, G. Eisenhofer, J. Pietzsch, M. Ullrich. J Cell Biotechnol. 2019;5:135-151.