Ken Herrmann1, Margret Schottelius2, Constantin Lapa3, Theresa Osl2, Andreas Poschenrieder2, Heribert Hänscheid3, Katharina Lückerath3, Martin Schreder4, Christina Bluemel3, Markus Knott4, Ulrich Keller5, Andreas Schirbel3, Samuel Samnick3, Michael Lassmann3, Saskia Kropf6, Andreas K Buck3, Hermann Einsele4, Hans-Juergen Wester2, Stefan Knop4. 1. Department of Nuclear Medicine, University Hospital Würzburg, Würzburg, Germany Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, Los Angeles, California Jonsson Comprehensive Cancer Center, David Geffen School of Medicine at UCLA, Los Angeles, California herrmann_k1@ukw.de. 2. Pharmaceutical Radiochemistry, Technische Universität München, Munich, Germany. 3. Department of Nuclear Medicine, University Hospital Würzburg, Würzburg, Germany. 4. Department of Internal Medicine II, Division of Hematology and Medical Oncology, Universitätsklinikum Würzburg, Würzburg, Germany. 5. Department of Medicine III (Hematology/Oncology), Technische Universität München, Munich, Germany German Cancer Consortium (DKTK) and Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Germany; and. 6. Scintomics GmbH, Fürstenfeldbruck, Germany.
Abstract
UNLABELLED: Chemokine receptor 4 (CXCR4) is a key factor for tumor growth and metastasis in several types of human cancer. Based on promising experiences with a radiolabeled CXCR4 ligand ((68)Ga-pentixafor) for diagnostic receptor targeting, (177)Lu- and (90)Y-pentixather were recently developed as endoradiotherapeutic vectors. Here, we summarize the first-in-human experience in 3 heavily pretreated patients with intramedullary and extensive extramedullary manifestations of multiple myeloma undergoing CXCR4-directed endoradiotherapy. METHODS: CXCR4 target expression was demonstrated by baseline (68)Ga-pentixafor PET. Each treatment was approved by the clinical ethics committee. Pretherapeutic (177)Lu-pentixather dosimetry was performed before (177)Lu-pentixather or (90)Y-pentixather treatment. Subsequently, patients underwent additional chemotherapy and autologous stem cell transplantation for bone marrow rescue. RESULTS: A remarkable therapeutic effect was visualized in 2 patients, who showed a significant reduction in (18)F-FDG uptake. CONCLUSION: CXCR4-targeted radiotherapy with pentixather appears to be a promising novel treatment option in combination with cytotoxic chemotherapy and autologous stem cell transplantation, especially for patients with advanced multiple myeloma.
UNLABELLED: Chemokine receptor 4 (CXCR4) is a key factor for tumor growth and metastasis in several types of humancancer. Based on promising experiences with a radiolabeled CXCR4 ligand ((68)Ga-pentixafor) for diagnostic receptor targeting, (177)Lu- and (90)Y-pentixather were recently developed as endoradiotherapeutic vectors. Here, we summarize the first-in-human experience in 3 heavily pretreated patients with intramedullary and extensive extramedullary manifestations of multiple myeloma undergoing CXCR4-directed endoradiotherapy. METHODS:CXCR4 target expression was demonstrated by baseline (68)Ga-pentixafor PET. Each treatment was approved by the clinical ethics committee. Pretherapeutic (177)Lu-pentixather dosimetry was performed before (177)Lu-pentixather or (90)Y-pentixather treatment. Subsequently, patients underwent additional chemotherapy and autologous stem cell transplantation for bone marrow rescue. RESULTS: A remarkable therapeutic effect was visualized in 2 patients, who showed a significant reduction in (18)F-FDG uptake. CONCLUSION:CXCR4-targeted radiotherapy with pentixather appears to be a promising novel treatment option in combination with cytotoxic chemotherapy and autologous stem cell transplantation, especially for patients with advanced multiple myeloma.
Authors: Rudolf A Werner; Alexander Weich; Andreas Schirbel; Samuel Samnick; Andreas K Buck; Takahiro Higuchi; Hans-Jürgen Wester; Constantin Lapa Journal: Eur J Nucl Med Mol Imaging Date: 2016-11-09 Impact factor: 9.236
Authors: Ken Herrmann; Markus Schwaiger; Jason S Lewis; Stephen B Solomon; Barbara J McNeil; Michael Baumann; Sanjiv S Gambhir; Hedvig Hricak; Ralph Weissleder Journal: Lancet Oncol Date: 2020-03 Impact factor: 41.316
Authors: Elizabeth M Jaffee; Chi Van Dang; David B Agus; Brian M Alexander; Kenneth C Anderson; Alan Ashworth; Anna D Barker; Roshan Bastani; Sangeeta Bhatia; Jeffrey A Bluestone; Otis Brawley; Atul J Butte; Daniel G Coit; Nancy E Davidson; Mark Davis; Ronald A DePinho; Robert B Diasio; Giulio Draetta; A Lindsay Frazier; Andrew Futreal; Sam S Gambhir; Patricia A Ganz; Levi Garraway; Stanton Gerson; Sumit Gupta; James Heath; Ruth I Hoffman; Cliff Hudis; Chanita Hughes-Halbert; Ramy Ibrahim; Hossein Jadvar; Brian Kavanagh; Rick Kittles; Quynh-Thu Le; Scott M Lippman; David Mankoff; Elaine R Mardis; Deborah K Mayer; Kelly McMasters; Neal J Meropol; Beverly Mitchell; Peter Naredi; Dean Ornish; Timothy M Pawlik; Jeffrey Peppercorn; Martin G Pomper; Derek Raghavan; Christine Ritchie; Sally W Schwarz; Richard Sullivan; Richard Wahl; Jedd D Wolchok; Sandra L Wong; Alfred Yung Journal: Lancet Oncol Date: 2017-10-31 Impact factor: 41.316
Authors: Sabine Maurer; Peter Herhaus; Romina Lippenmeyer; Heribert Hänscheid; Malte Kircher; Andreas Schirbel; H Carlo Maurer; Andreas K Buck; Hans-Jürgen Wester; Hermann Einsele; Götz-Ulrich Grigoleit; Ulrich Keller; Constantin Lapa Journal: J Nucl Med Date: 2019-03-08 Impact factor: 10.057
Authors: Peter Herhaus; Stefan Habringer; Kathrin Philipp-Abbrederis; Tibor Vag; Carlos Gerngross; Margret Schottelius; Julia Slotta-Huspenina; Katja Steiger; Torben Altmann; Tanja Weißer; Sabine Steidle; Markus Schick; Laura Jacobs; Jolanta Slawska; Catharina Müller-Thomas; Mareike Verbeek; Marion Subklewe; Christian Peschel; Hans-Jürgen Wester; Markus Schwaiger; Katharina Götze; Ulrich Keller Journal: Haematologica Date: 2016-05-12 Impact factor: 9.941