ImmunoPET (Positron Emission Tomography) has been specifically identified in Blue Ribbon Panel report (pg 53) as a transformative research recommendation for achieving Cancer Moonshot?s ambitious goal of making a decade?s worth of progress in 5 years. The broad long-term objective of this application is to expand availability of ImmunoPET from select few top-tier research centers to the broad cancer patient population across the US. The main issue preventing such expansion today is rooted in production complexity of ImmunoPET tracers, radioactively labeled antibodies used as contrast agents. These activities are directly related to the mission of the NCI. Trace-Ability proposes to automate the entire production procedure including radio-labeling, QC and immunoassay with results available before the PET scan. Production staff will need only to add the radionuclide, initiate the process and return to collect the product along with QC report. Such solution will enable more facilities to produce ImmunoPET tracers, each facility to support more patients and fewer patients having to repeat scans due to low immunoreactivity of the tracer. Tracer-QC is a radically-innovative automated solution for QC of PET tracers based on integration of plate reader, liquid handler and HPLC machine. A kit of reagents and consumables enables hands-free operation. Tracer-QC platform will be used to automate the complete production process including synthesis, QC and pre-release immunoreactivity. The level of automation in the resulting system was previously inconceivable because traditional synthesis and QC processes rely on highly specialized procedures and cannot share system components. New capabilities that need to be enabled on Tracer-QC for ImmunoPET applications are radiolabeling and immunoreactivity assay. PET tracer chosen for this project is [89Zr]DFO-Pembrolizumab, targeting PD-1 receptors expressed on the surface of activated T-cells, proposed based on the breadth of its applications in cancer imaging.
Specific Aim 1 : Demonstrate feasibility of automated [89Zr]DFO-Pembrolizumab synthesis on Tracer-QC platform. Radiolabeling, which falls outside of QC procedure scope has never been enabled on Tracer-QC, although it appears conceptually feasible. Quantitative milestones: (a) Automated synthesis of [89Zr]DFO-Pembrolizumab starting with [89Zr]-oxalate finished using only Tracer-QC and no manual operations. (b) 70% Radiochemical yield.
Specific Aim 2 : Demonstrate complete [89Zr]DFO- Pembrolizumab QC performed on Tracer-QC. QC of antibody-based tracers includes tests similar to FDG plus a binding assay that takes 24-48h. Quantitative milestones: (a) Binding affinity measured by Tracer- QC and traditional method agree within 20%. (b) Binding assay completed in < 3 hours. (c) Demonstration of all other [89Zr]DFO-Pembrolizumab QC measurements on Tracer-QC.
By expanding availability of ImmunoPET (Positron Emission Tomography imaging based on radio- labeled antibodies) to broad cancer population, proposed work enables timely and more educated treatment decisions that should lead to improved outcomes. Furthermore, by dramatically simplifying production of radio-labeled antibodies, this project enables further research in ImmunoPET field as directed by the Cancer Moonshot Initiative Blue Ribbon Panel report.
