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

  • J Nucl Med. 2016 Feb;57(2):248-51. doi: 10.2967/jnumed.115.167361.
Ken Herrmann  1 ,  Margret Schottelius  2 ,  Constantin Lapa  3 ,  Theresa Osl  2 ,  Andreas Poschenrieder  2 ,  Heribert Hänscheid  3 ,  Katharina Lückerath  3 ,  Martin Schreder  4 ,  Christina Bluemel  3 ,  Markus Knott  4 ,  Ulrich Keller  5 ,  Andreas Schirbel  3 ,  Samuel Samnick  3 ,  Michael Lassmann  3 ,  Saskia Kropf  6 ,  Andreas K Buck  3 ,  Hermann Einsele  4 ,  Hans-Juergen Wester  2 ,  Stefan Knop  4
Affiliations
  • 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 [email protected].
  • 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.
PMID: 26564323 DOI: 10.2967/jnumed.115.167361
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.

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.

Keywords
CXCR4; endoradiotherapy; multiple myeloma; pentixather.
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