Immuno-PET is a molecular imaging technique utilizing positron emission tomography (PET) to measure the biodistribution of an antibody species labeled with a radioactive isotope. When applied as a clinical imaging technique, an immuno-PET imaging agent must be manufactured with quality standards appropriate for regulatory approval. This paper describes methods relevant to the chemistry, manufacturing, and controls component of an immuno-PET regulatory filing, such as an investigational new drug application. Namely, the production, quality control, and characterization of the immuno-PET clinical imaging agent, ZED8, an 89Zr-labeled CD8-specific monovalent antibody as well as its desferrioxamine-conjugated precursor, CED8, is described and evaluated. PET imaging data in a human CD8-expressing tumor murine model is presented as a proof of concept that the imaging agent exhibits target specificity and comparable biodistribution across a range of desferrioxamine conjugate loads.
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Mark Dennis, Yvonne Chen, Diego Ellerman, Phil Hass, Maciej Paluch (Genentech Research and Early Development) – production of anti-CD8 monovalent antibody, anti-gD monovalent antibody, and human CD8-Fc fusion protein for pre-clinical evaluation; Pat Mckay (Genentech Pharmaceutical Technical Development) - production of human CD8-Fc fusion protein; Bruce Kabakoff, Devon Roshan Eisner (Genentech Pharmaceutical Technical Development) –guidance on the formulation buffer, stability, and container closure integrity studies.
All authors are paid employees of either Genentech Inc. or InviCRO, LLC and all work was funded by Genentech Inc.
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Gill, H., Seipert, R., Carroll, V.M. et al. The Production, Quality Control, and Characterization of ZED8, a CD8-Specific 89Zr-Labeled Immuno-PET Clinical Imaging Agent. AAPS J 22, 22 (2020). https://doi.org/10.1208/s12248-019-0392-0
- Positron Emission Tomography
- cancer immunotherapy
- manufacturing, and controls
- clinical trial