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

Albert Lockhart, Yongjian Liu, Farrokh Dehdashti, Richard Laforest, Joel Picus, Jennifer Frye, Lauren Trull, Stefanie Belanger, Madhuri Desai, Syed Mahmood, Jeanne Mendell, Michael J. Welch, Barry A. Siegel

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Purpose: The purpose of this study was to evaluate the safety, dosimetry, and apparent receptor occupancy (RO) of [64Cu]DOTA-patritumab, a radiolabeled monoclonal antibody directed against HER3/ERBB3 in subjects with advanced solid tumors. Procedures: Dosimetry subjects (n = 5) received [64Cu]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 [64Cu]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: [64Cu]DOTA-patritumab was safe. These limited results suggest that this PET-based method can be used to determine tumor-apparent RO.

Original languageEnglish (US)
Pages (from-to)446-453
Number of pages8
JournalMolecular Imaging and Biology
Volume18
Issue number3
DOIs
StatePublished - Jun 1 2016
Externally publishedYes

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Safety
Neoplasms
Positron-Emission Tomography
X Ray Computed Tomography
U3-1287
Monoclonal Antibodies
Injections
Liver

Keywords

  • Dosimetry
  • Human epidermal growth factor receptor 3
  • Patritumab
  • PET/CT
  • Phase 1
  • Receptor occupancy
  • [Cu]DOTA-patritumab

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

Cite this

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

In: Molecular Imaging and Biology, Vol. 18, No. 3, 01.06.2016, p. 446-453.

Research output: Contribution to journalArticle

Lockhart, A, Liu, Y, Dehdashti, F, Laforest, R, Picus, J, Frye, J, Trull, L, Belanger, S, Desai, M, Mahmood, S, Mendell, J, Welch, MJ & Siegel, BA 2016, 'Phase 1 Evaluation of [64Cu]DOTA-Patritumab to Assess Dosimetry, Apparent Receptor Occupancy, and Safety in Subjects with Advanced Solid Tumors', Molecular Imaging and Biology, vol. 18, no. 3, pp. 446-453. https://doi.org/10.1007/s11307-015-0912-y
Lockhart, Albert ; 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. / Phase 1 Evaluation of [64Cu]DOTA-Patritumab to Assess Dosimetry, Apparent Receptor Occupancy, and Safety in Subjects with Advanced Solid Tumors. In: Molecular Imaging and Biology. 2016 ; Vol. 18, No. 3. pp. 446-453.
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abstract = "Purpose: The purpose of this study was to evaluate the safety, dosimetry, and apparent receptor occupancy (RO) of [64Cu]DOTA-patritumab, a radiolabeled monoclonal antibody directed against HER3/ERBB3 in subjects with advanced solid tumors. Procedures: Dosimetry subjects (n = 5) received [64Cu]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 [64Cu]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: [64Cu]DOTA-patritumab was safe. These limited results suggest that this PET-based method can be used to determine tumor-apparent RO.",
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AU - Liu, Yongjian

AU - Dehdashti, Farrokh

AU - Laforest, Richard

AU - Picus, Joel

AU - Frye, Jennifer

AU - Trull, Lauren

AU - Belanger, Stefanie

AU - Desai, Madhuri

AU - Mahmood, Syed

AU - Mendell, Jeanne

AU - Welch, Michael J.

AU - Siegel, Barry A.

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