title: Phase 1 Evaluation of [(64)Cu]DOTA-Patritumab to Assess Dosimetry, Apparent Receptor Occupancy, and Safety in Subjects with Advanced Solid Tumors.
abstract: 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.
  
  
  
  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.
  
  
  
  The tumor SUVmax (± 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.
  
  
  
  [(64)Cu]DOTA-patritumab was safe. These limited results suggest that this PET-based method can be used to determine tumor-apparent RO.
authors.affiliation: Alvin J. Siteman Cancer Center, Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8056, St. Louis, MO, 63110, USA. alockhar@dom.wustl.edu.|Division of Oncology, Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8056, St. Louis, MO, 63110, USA. alockhar@dom.wustl.edu.
authors.forename: A Craig
authors.initials: AC
authors.lastname: Lockhart
authors.affiliation: Alvin J. Siteman Cancer Center, Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8056, St. Louis, MO, 63110, USA.|Mallinckrodt Institute of Radiology, Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8056, St. Louis, MO, 63110, USA.
authors.forename: Yongjian
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Alvin J. Siteman Cancer Center, Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8056, St. Louis, MO, 63110, USA.|Mallinckrodt Institute of Radiology, Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8056, St. Louis, MO, 63110, USA.
authors.forename: Farrokh
authors.initials: F
authors.lastname: Dehdashti
authors.affiliation: Alvin J. Siteman Cancer Center, Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8056, St. Louis, MO, 63110, USA.|Mallinckrodt Institute of Radiology, Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8056, St. Louis, MO, 63110, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Laforest
authors.affiliation: Alvin J. Siteman Cancer Center, Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8056, St. Louis, MO, 63110, USA.|Division of Oncology, Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8056, St. Louis, MO, 63110, USA.
authors.forename: Joel
authors.initials: J
authors.lastname: Picus
authors.affiliation: Mallinckrodt Institute of Radiology, Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8056, St. Louis, MO, 63110, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Frye
authors.affiliation: Division of Oncology, Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8056, St. Louis, MO, 63110, USA.
authors.forename: Lauren
authors.initials: L
authors.lastname: Trull
authors.affiliation: Division of Oncology, Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8056, St. Louis, MO, 63110, USA.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Belanger
authors.affiliation: Daiichi-Sankyo Pharma Development, Edison, NJ, USA.
authors.forename: Madhuri
authors.initials: M
authors.lastname: Desai
authors.affiliation: Daiichi-Sankyo Pharma Development, Edison, NJ, USA.
authors.forename: Syed
authors.initials: S
authors.lastname: Mahmood
authors.affiliation: Daiichi-Sankyo Pharma Development, Edison, NJ, USA.
authors.forename: Jeanne
authors.initials: J
authors.lastname: Mendell
authors.affiliation: Alvin J. Siteman Cancer Center, Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8056, St. Louis, MO, 63110, USA.|Mallinckrodt Institute of Radiology, Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8056, St. Louis, MO, 63110, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Welch
authors.affiliation: Alvin J. Siteman Cancer Center, Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8056, St. Louis, MO, 63110, USA.|Mallinckrodt Institute of Radiology, Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8056, St. Louis, MO, 63110, USA.
authors.forename: Barry A
authors.initials: BA
authors.lastname: Siegel
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D057134:Antibodies, Neutralizing / Q000009:adverse effects* / Q000627:therapeutic use*; D000080908:Broadly Neutralizing Antibodies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009369:Neoplasms / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000473:pathology; D009942:Organometallic Compounds / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D049268:Positron-Emission Tomography; D011874:Radiometry; D011956:Receptors, Cell Surface; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome
chemical_list: C000622703:64Cu-DOTA-patritumab; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D057134:Antibodies, Neutralizing; D000080908:Broadly Neutralizing Antibodies; D009942:Organometallic Compounds; D011956:Receptors, Cell Surface; C585471:patritumab
keywords: Dosimetry; Human epidermal growth factor receptor 3; PET/CT; Patritumab; Phase 1; Receptor occupancy; [64Cu]DOTA-patritumab