Safety and Stability of Antibody-Dye Conjugate in Optical Molecular Imaging
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RESEARCH ARTICLE
Safety and Stability of Antibody-Dye Conjugate in Optical Molecular Imaging Jacqueline Pei,1 Georgina Juniper,1 Nynke S. van den Berg,1 Naoki Nisho,1 Trevor Broadt,2 Anthony R. Welch,3 Grace S. Yi,1 Roan C. Raymundo,1 Stefania U. Chirita,1 Guolan Lu,1 Giri Krishnan,1 Yu-Jin Lee,1 Shrey Kapoor,1 Quan Zhou,1,4 A. Dimitrios Colevas,1 Natalie S. Lui,5 George A. Poultsides,6 Gordon Li,4 Kurt R. Zinn,7 Eben L. Rosenthal 1 1
Department of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, 900 Blake Wilbur Drive, Stanford, CA, 94305, USA 2 Biopharmaceutical Development Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD, USA 3 Biological Resources Branch/DTP/DCTD, National Cancer Institute, Frederick, MD, USA 4 Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA, USA 5 Department of Cardiothoracic Surgery, Stanford University School of Medicine, Stanford, CA, USA 6 Department of Surgery, Section of Surgical Oncology, Stanford University School of Medicine, Stanford, CA, USA 7 Department of Radiology, Institute for Quantitative Health Science and Engineering, Michigan State University, East Lansing, MI, USA
Abstract Purpose: The development of molecularly targeted tracers is likely to improve the accuracy of diagnostic, screening, and therapeutic tools. Despite the many therapeutic antibodies that are FDA-approved with known toxicity, only a limited number of antibody-dye conjugates have been introduced to the clinic. Thorough evaluation of the safety, stability, and pharmacokinetics of antibody conjugates in the clinical setting compared with their parental components could accelerate the clinical approval of antibodies as agents for molecular imaging. Here we investigate the safety and stability of a near-infrared fluorescent dye (IRDye800CW) conjugated panitumumab, an approved therapeutic antibody, and report on the product stability, pharmacokinetics, adverse events, and QTc interval changes in patients. Procedures: Panitumumab-IRDye800CW was made under good manufacturing practice (GMP) conditions in a single batch on March 26, 2014, and then evaluated over 4.5 years at 0, 3, and 6 months, and then at 6-month intervals thereafter. We conducted early phase trials in head and neck, lung, pancreas, and brain cancers with panitumumab-IRDye800CW. Eighty-one patients scheduled to undergo standard-of-care surgery were infused with doses between 0.06 to 2.83 mg/kg of antibody. Patient ECGs, blood samples, and adverse events were collected over 30-day post-infusion for analysis.
Jacqueline Pei and Georgina Juniper contributed equally to this work. Jacqueline Pei and Georgina Juniper share first authorship Electronic supplementary material The online version of this article (https:// doi.org/10.1007/s11307-020-01536-2) contains supplementary material, which is available to authorized users. Correspondence to: Eben Rosenthal; e-mail: [email protected]
Pei J. et al.: Safety and Stability of Antibody-
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