title: First-in-Human Experience of CXCR4-Directed Endoradiotherapy with 177Lu- and 90Y-Labeled Pentixather in Advanced-Stage Multiple Myeloma with Extensive Intra- and Extramedullary Disease.
abstract: 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.
  
  
  CONCLUSIONS
  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.affiliation: 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.
authors.forename: Ken
authors.initials: K
authors.lastname: Herrmann
authors.affiliation: Pharmaceutical Radiochemistry, Technische Universität München, Munich, Germany.
authors.forename: Margret
authors.initials: M
authors.lastname: Schottelius
authors.affiliation: Department of Nuclear Medicine, University Hospital Würzburg, Würzburg, Germany.
authors.forename: Constantin
authors.initials: C
authors.lastname: Lapa
authors.affiliation: Pharmaceutical Radiochemistry, Technische Universität München, Munich, Germany.
authors.forename: Theresa
authors.initials: T
authors.lastname: Osl
authors.affiliation: Pharmaceutical Radiochemistry, Technische Universität München, Munich, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Poschenrieder
authors.affiliation: Department of Nuclear Medicine, University Hospital Würzburg, Würzburg, Germany.
authors.forename: Heribert
authors.initials: H
authors.lastname: Hänscheid
authors.affiliation: Department of Nuclear Medicine, University Hospital Würzburg, Würzburg, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Lückerath
authors.affiliation: Department of Internal Medicine II, Division of Hematology and Medical Oncology, Universitätsklinikum Würzburg, Würzburg, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Schreder
authors.affiliation: Department of Nuclear Medicine, University Hospital Würzburg, Würzburg, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Bluemel
authors.affiliation: Department of Internal Medicine II, Division of Hematology and Medical Oncology, Universitätsklinikum Würzburg, Würzburg, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Knott
authors.affiliation: Department of Medicine III (Hematology/Oncology), Technische Universität München, Munich, Germany German Cancer Consortium (DKTK) and Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Germany; and.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Keller
authors.affiliation: Department of Nuclear Medicine, University Hospital Würzburg, Würzburg, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Schirbel
authors.affiliation: Department of Nuclear Medicine, University Hospital Würzburg, Würzburg, Germany.
authors.forename: Samuel
authors.initials: S
authors.lastname: Samnick
authors.affiliation: Department of Nuclear Medicine, University Hospital Würzburg, Würzburg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Lassmann
authors.affiliation: Scintomics GmbH, Fürstenfeldbruck, Germany.
authors.forename: Saskia
authors.initials: S
authors.lastname: Kropf
authors.affiliation: Department of Nuclear Medicine, University Hospital Würzburg, Würzburg, Germany.
authors.forename: Andreas K
authors.initials: AK
authors.lastname: Buck
authors.affiliation: Department of Internal Medicine II, Division of Hematology and Medical Oncology, Universitätsklinikum Würzburg, Würzburg, Germany.
authors.forename: Hermann
authors.initials: H
authors.lastname: Einsele
authors.affiliation: Pharmaceutical Radiochemistry, Technische Universität München, Munich, Germany.
authors.forename: Hans-Juergen
authors.initials: HJ
authors.lastname: Wester
authors.affiliation: Department of Internal Medicine II, Division of Hematology and Medical Oncology, Universitätsklinikum Würzburg, Würzburg, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Knop
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D016026:Bone Marrow Transplantation; D003131:Combined Modality Therapy; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000000981:diagnostic imaging / Q000532:radiotherapy*; D009362:Neoplasm Metastasis; D010455:Peptides / Q000627:therapeutic use*; D011874:Radiometry; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000627:therapeutic use*; D019718:Receptors, CXCR4 / Q000187:drug effects*; D016896:Treatment Outcome
chemical_list: C000608226:177Lu-pentixather; C000608227:90Y-pentixather; D000970:Antineoplastic Agents; D010455:Peptides; D019275:Radiopharmaceuticals; D019718:Receptors, CXCR4; D019788:Fluorodeoxyglucose F18
keywords: CXCR4; endoradiotherapy; multiple myeloma; pentixather