GRK 1739 - Research Projects

Project 13Identifying and targeting resistance mechanisms to 177Lu-PSMA radioligand therapy of metastatic prostate cancer

Principle Investigator

Prof. Dr. med. Ken Herrmann

Clinic for Nuclear Medicine
Essen University Hospital

Prof. Dr. Ken Herrmann


The group of Ken Herrmann focuses on translation of theranostic concepts using radioactively labelled peptide analogues to diagnose and treat cancer. Somatostatin receptor targeted theranostic has recently been approved based on accurate diagnosis and effective therapy of patients with neuroendocrine tumors (NETs). More recently, highly specific ligands binding to the prostate specific membrane antigen (PSMA) have been developed. PSMA is a plasma membrane glycoprotein expressed at high levels on the surface of prostate cancer cells. 177Lu-PSMA617 radioligand therapy (RLT) reduces tumor load in more than 50% of patients and improves pain and quality of life. However, more than one third of patients will not respond to 177Lu-PSMA617 RLT. Initial responders to RLT demonstrate recurrence after delays in disease progression. Hence, there is a need to understand and target resistance to 177Lu-PSMA617 RLT. This project investigates RLT resistance mechanisms in preclinical models of mCRPC. This project attempts to identify relevant pathways of resistance and aims to overcome those.

Selected Publications

Herrmann K, Wieder HA, Buck AK, Schoffel M, Krause BJ, Fend F, Schuster T, Meyer zum Buschenfelde C, Wester HJ, Duyster J, Peschel C, Schwaiger M, Dechow T. Early response assessment using 3'-deoxy-3'-[18F]fluorothymidine-positron emission tomography in high-grade non-Hodgkin's lymphoma. Clin Cancer Res. 2007;13:3552-3558.

Lordick F, Ott K, Krause BJ, Weber WA, Becker K, Stein HJ, Lorenzen S, Schuster T, Wieder H, Herrmann K, Bredenkamp R, Hofler H, Fink U, Peschel C, Schwaiger M, Siewert JR. PET to assess early metabolic response and to guide treatment of adenocarcinoma of the oesophagogastric junction: the MUNICON phase II trial. Lancet Oncol. 2007;8:797-805.

*Buck AK, Herrmann K, Buschenfelde CM, Juweid ME, Bischoff M, Glatting G, Weirich G, Moller P, Wester HJ, Scheidhauer K, Dechow T, Peschel C, Schwaiger M, Reske SN. Imaging bone and soft tissue tumors with the proliferation marker [18F]fluorodeoxythymidine. Clin Cancer Res. 2008;14:2970-2977.

*Ott K, Herrmann K, Lordick F, Wieder H, Weber WA, Becker K, Buck AK, Dobritz M, Fink U, Ulm K, Schuster T, Schwaiger M, Siewert JR, Krause BJ. Early metabolic response evaluation by fluorine-18 fluorodeoxyglucose positron emission tomography allows in vivo testing of chemosensitivity in gastric cancer: long-term results of a prospective study. Clin Cancer Res. 2008;14:2012-2018.

Herrmann K, Benz MR, Czernin J, Allen-Auerbach MS, Tap WD, Dry SM, Schuster T, Eckardt JJ, Phelps ME, Weber WA, Eilber FC. 18F-FDG-PET/CT Imaging as an early survival predictor in patients with primary high-grade soft tissue sarcomas undergoing neoadjuvant therapy. Clin Cancer Res. 2012;18:2024-2031.

Lapa C, Luckerath K, Kleinlein I, Monoranu CM, Linsenmann T, Kessler AF, Rudelius M, Kropf S, Buck AK, Ernestus RI, Wester HJ, Lohr M, Herrmann K. (68)Ga-Pentixafor-PET/CT for Imaging of Chemokine Receptor 4 Expression in Glioblastoma. Theranostics. 2016;6:428-434.

Wei W, Shin YS, Xue M, Matsutani T, Masui K, Yang H, Ikegami S, Gu Y, Herrmann K, Johnson D, Ding X, Hwang K, Kim J, Zhou J, Su Y, Li X, Bonetti B, Chopra R, James CD, Cavenee WK, Cloughesy TF, Mischel PS, Heath JR, Gini B. Single-Cell Phosphoproteomics Resolves Adaptive Signaling Dynamics and Informs Targeted Combination Therapy in Glioblastoma. Cancer Cell. 2016;29:563-573.

Barrio MJ, Spick C, Radu CG, Lassmann M, Eberlein U, Allen-Auerbach M, Schiepers C, Slavik R, Czernin J, Herrmann K. Human Biodistribution and Radiation Dosimetry of (18)F-Clofarabine, a PET Probe Targeting the Deoxyribonucleoside Salvage Pathway. J Nucl Med. 2017;58:374-378.

Calais J, Fendler WP, Eiber M, Gartmann J, Chu FI, Nickols NG, Reiter RR, Rettig MB, Marks LS, Ahlering TE, Huynh L, Slavik R, Gupta P, Quon A, Allen-Auerbach MS, Czernin J, Herrmann K. Actual impact of (68)Ga-PSMA-11 PET/CT on the management of prostate cancer patients with biochemical recurrence. J Nucl Med. 2017.

Calais J, Czernin J, Eiber M, Fendler WP, Gartmann J, Heaney AP, Hendifar AE, Pisegna JR, Hecht JR, Wolin EM, Slavik R, Gupta P, Quon A, Schiepers C, Allen-Auerbach MS, Herrmann K. Most of the Intended Management Changes After (68)Ga-DOTATATE PET/CT Are Implemented. J Nucl Med. 2017;58:1793-1796.

*shared first author