89Zr-Lumretuzumab PET Imaging before and during HER3 Antibody Lumretuzumab Treatment in Patients with Solid Tumors

Abstract

<b>Purpose:</b> 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.<b>Experimental Design:</b> 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).<b>Results:</b> 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 (<i>n</i> = 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.<b>Conclusions:</b> 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. <i>Clin Cancer Res; 23(20); 6128-37. ©2017 AACR</i>.