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  • [Clin Cancer Res.] 89Zr-Lumretuzumab PET Imaging before and during HER3 Antibody Lumretuzumab Treatment in Patients with Solid Tumors.

    University Medical Center Groningen / Elisabeth G.E. de Vries*

  • 출처
    Clin Cancer Res.
  • 등재일
    2017 Oct 15
  • 저널이슈번호
    23(20):6128-6137.
  • 내용

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    Abstract

     

    Purpose:

    We evaluated biodistribution and tumor targeting of 89Zr-lumretuzumab before and during treatment with lumretuzumab, a human epidermal growth factor receptor 3 (HER3)-targeting monoclonal antibody.

     

    Experimental Design: 

    Twenty patients with histologically confirmed HER3-expressing tumors received 89Zr-lumretuzumab and underwent positron emission tomography (PET). In part A, 89Zr-lumretuzumab was given with additional, escalating doses of unlabeled lumretuzumab, and scans were performed 2, 4, and 7 days after injection to determine optimal imaging conditions. In part B, patients were scanned following tracer injection before (baseline) and after a pharmacodynamic (PD)-active lumretuzumab dose for saturation analysis. HER3 expression was determined immunohistochemically in skin biopsies. Tracer uptake was calculated as standardized uptake value (SUV).

     

    Results:

    Optimal PET conditions were found to be 4 and 7 days after administration of 89Zr-lumretuzumab with 100-mg unlabeled lumretuzumab. At baseline using 100-mg unlabeled lumretuzumab, the tumor SUVmax was 3.4 (±1.9) at 4 days after injection. SUVmean values for normal blood, liver, lung, and brain tissues were 4.9, 6.4, 0.9 and 0.2, respectively. Saturation analysis (n = 7) showed that 4 days after lumretuzumab administration, tumor uptake decreased by 11.9% (±8.2), 10.0% (±16.5), and 24.6% (±20.9) at PD-active doses of 400, 800, and 1,600 mg, respectively, when compared with baseline. Membranous HER3 was completely downregulated in paired skin biopsies already at and above 400-mg lumretuzumab.

     

    Conclusions: 

    PET imaging showed biodistribution and tumor-specific 89Zr-lumretuzumab uptake. Although, PD-active lumretuzumab doses decreased 89Zr-lumretuzumab uptake, there was no clear evidence of tumor saturation by PET imaging as the tumor SUV did not plateau with increasing doses.

     

    Author information

    Bensch F1, Lamberts LE1, Smeenk MM1, Jorritsma-Smit A2, Lub-de Hooge MN2,3, Terwisscha van Scheltinga AGT2, de Jong JR3, Gietema JA1, Schröder CP1, Thomas M4, Jacob W4, Abiraj K5, Adessi C5, Meneses-Lorente G6, James I7, Weisser M4, Brouwers AH3, de Vries EGE8.

    Department of Medical Oncology, University of Groningen, University Medical Center Groningen, the Netherlands.

    Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, the Netherlands.

    Department of Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Center Groningen, the Netherlands.

    Pharma Research and Early Development, Roche Innovation Center Munich, Penzberg, Germany.

    Pharma Research and Early Development, Roche Innovation Center Basel, Basel, Switzerland.

    Pharma Research and Early Development, Roche Innovation Center Welwyn, Welwyn, United Kingdom.

    A4P Consulting Ltd, Sandwich, United Kingdom.

    Department of Medical Oncology, University of Groningen, University Medical Center Groningen, the Netherlands. e.g.e.de.vries@umcg.nl. 

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