Phase 1 Evaluation of [64Cu]DOTA-Patritumab to Assess Dosimetry, Apparent Receptor Occupancy, and Safety in Subjects with Advanced Solid Tumors

• Published in: Molecular imaging and biology Vol. 18; no. 3; pp. 446 - 453
• Main Authors: Lockhart, A. Craig, Liu, Yongjian, Dehdashti, Farrokh, Laforest, Richard, Picus, Joel, Frye, Jennifer, Trull, Lauren, Belanger, Stefanie, Desai, Madhuri, Mahmood, Syed, Mendell, Jeanne, Welch, Michael J., Siegel, Barry A.
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.06.2016; Springer Nature B.V
• Subjects: Adult; Aged; Antibodies, Monoclonal - adverse effects; Antibodies, Monoclonal - pharmacokinetics; Antibodies, Monoclonal - therapeutic use; Antibodies, Monoclonal, Humanized; Antibodies, Neutralizing - adverse effects; Antibodies, Neutralizing - therapeutic use; Broadly Neutralizing Antibodies; Female; Humans; Imaging; Male; Medicine; Medicine & Public Health; Middle Aged; Neoplasm Staging; Neoplasms - diagnostic imaging; Neoplasms - drug therapy; Neoplasms - pathology; Organometallic Compounds - adverse effects; Organometallic Compounds - pharmacokinetics; Organometallic Compounds - therapeutic use; Positron-Emission Tomography; Radiology; Radiometry; Receptors, Cell Surface; Research Article; Tomography, X-Ray Computed; Treatment Outcome; Human epidermal growth factor receptor 3; Patritumab; Cu]DOTA-patritumab; PET/CT; [; Phase 1; Dosimetry; Receptor occupancy; [64Cu]DOTA-patritumab
• ISSN: 1536-1632; 1860-2002
• DOI: 10.1007/s11307-015-0912-y

Purpose The purpose of this study was to evaluate the safety, dosimetry, and apparent receptor occupancy (RO) of [ 64 Cu]DOTA-patritumab, a radiolabeled monoclonal antibody directed against HER3/ERBB3 in subjects with advanced solid tumors. Procedures Dosimetry subjects ( n  = 5) received [ 64 Cu]DOTA-patritumab and underwent positron emission tomography (PET)/X-ray computed tomography (CT) at 3, 24, and 48 h. Evaluable RO subjects ( n  = 3 out of 6) received [ 64 Cu]DOTA-patritumab at day 1 and day 8 (after 9.0 mg/kg patritumab) followed by PET/CT at 24 h post-injection. Endpoints included safety, tumor uptake, and efficacy. Results The tumor SUV max (± SD) was 5.6 ± 4.5, 3.3 ± 1.7, and 3.0 ± 1.1 at 3, 24, and 48 h in dosimetry subjects. The effective dose and critical organ dose (liver) averaged 0.044 ± 0.008 mSv/MBq and 0.46 ± 0.086 mGy/MBq, respectively. In RO subjects, tumor-to-blood ratio decreased from 1.00 ± 0.32 at baseline to 0.57 ± 0.17 after stable patritumab, corresponding to a RO of 42.1 ± 3. Conclusions [ 64 Cu]DOTA-patritumab was safe. These limited results suggest that this PET-based method can be used to determine tumor-apparent RO.