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

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]DOT...

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Publicado en:Molecular Imaging & Biology Vol. 18; no. 3; pp. 446 - 454
Autores principales: Lockhart, A., Liu, Yongjian, Dehdashti, Farrokh, Laforest, Richard, Picus, Joel, Frye, Jennifer, Trull, Lauren, Belanger, Stefanie, Desai, Madhuri, Mahmood, Syed, Mendell, Jeanne, Welch, Michael, Siegel, Barry, Lockhart, A Craig, Welch, Michael J, Siegel, Barry A
Formato: clinical trial research Journal Article
Publicado: Springer Nature Jun2016
Acceso en línea:Ver este registro en EBSCOhost
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      dt: Jun2016
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      pub: Springer Nature
      place: New York, New York
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        atl: Phase 1 Evaluation of [(64)Cu]DOTA-Patritumab to Assess Dosimetry, Apparent Receptor Occupancy, and Safety in Subjects with Advanced Solid Tumors.
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        au:
          Lockhart, A.
          Liu, Yongjian
          Dehdashti, Farrokh
          Laforest, Richard
          Picus, Joel
          Frye, Jennifer
          Trull, Lauren
          Belanger, Stefanie
          Desai, Madhuri
          Mahmood, Syed
          Mendell, Jeanne
          Welch, Michael
          Siegel, Barry
          Lockhart, A Craig
          Welch, Michael J
          Siegel, Barry A
        affil: Mallinckrodt Institute of Radiology, Washington University School of Medicine, 660 South Euclid Avenue St. Louis 63110 USA
      sug:
        subj:
          Antibodies Therapeutic Use
          Antibodies, Monoclonal Therapeutic Use
          Neoplasms
          Organometallic Compounds Adverse Effects
          Organometallic Compounds Therapeutic Use
          Antibodies Adverse Effects
          Radiometry
          Neoplasms Drug Therapy
          Antibodies, Monoclonal Adverse Effects
          Treatment Outcomes
          Tomography, Emission-Computed
          Organometallic Compounds Pharmacokinetics
          Human
          Receptors, Cell Surface
          Neoplasms Pathology
          Adult
          Antibodies, Monoclonal
          Middle Age
          Female
          Male
          Tomography, X-Ray Computed
          Neoplasm Staging
          Aged
          Clinical Trials
          Validation Studies
          Comparative Studies
          Evaluation Research
          Multicenter Studies
          Adult: 19-44 years
          Middle Aged: 45-64 years
          Aged: 65+ years
          Female
          Male
      ab: 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 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.Conclusions: [(64)Cu]DOTA-patritumab was safe. These limited results suggest that this PET-based method can be used to determine tumor-apparent RO.
      pubtype: Academic Journal
      doctype:
        clinical trial
        research
        Journal Article
      ougenre: Article
    language: English
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