TY - JOUR
T1 - Phase 1 Evaluation of [64Cu]DOTA-Patritumab to Assess Dosimetry, Apparent Receptor Occupancy, and Safety in Subjects with Advanced Solid Tumors
AU - Lockhart, A. Craig
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.
N1 - Publisher Copyright:
© 2015, World Molecular Imaging Society.
PY - 2016/6/1
Y1 - 2016/6/1
N2 - 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.
AB - 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.
KW - Dosimetry
KW - Human epidermal growth factor receptor 3
KW - PET/CT
KW - Patritumab
KW - Phase 1
KW - Receptor occupancy
KW - [Cu]DOTA-patritumab
UR - http://www.scopus.com/inward/record.url?scp=84946935104&partnerID=8YFLogxK
U2 - 10.1007/s11307-015-0912-y
DO - 10.1007/s11307-015-0912-y
M3 - Article
C2 - 26567113
AN - SCOPUS:84946935104
SN - 1536-1632
VL - 18
SP - 446
EP - 453
JO - Molecular Imaging and Biology
JF - Molecular Imaging and Biology
IS - 3
ER -