SBIR-STTR Award

PET is a molecular imaging modality that utilizes trace amounts of radiolabeled molecules ([unreadable]probes[unreadable]) to target, measure, and image biological processes in tissue concentrations down to the range of nano-[unreadable]‐to picomoles. Imaging technologies from SOFIE and other companies allow the same probes to be used in cell cultures, mice, and patients to integrate findings from each of these settings with other basic science and clinical results. UCLA investigators developed, and licensed to SOFIE for further commercialization, a family of nucleoside analog probes ([18F]FAC) that are transported and trapped intracellularly by dCK phosphorylation. SOFIE and others can now reference UCLA INDs for these probes, allowing further investigation into [18F]FAC as diagnostic agents for assaying dCK enzyme activity in predicting tumor responses to dCK dependent prodrugs. One potential roadblock to widespread use of this probe is that no commercial radiosynthesizer exists for synthesizing [18F]FAC for pre-[unreadable]‐clinical and clinical investigations. This proposal will also develop a commercial, cGMP-[unreadable]‐friendly, automated radiosynthesizer to produce [18F]FAC. Therefore, the deliverables of this project are approaches and technologies broadly applicable to predicting tumor responses to dCK dependent nucleoside prodrugs that are widely used in treatment of cancer and under investigation in a large number of trials.

Positron Emission Tomography (PET) is a molecular imaging modality that utilizes radiolabeled molecules (“probes”) to target and measure biological processes. Researchers can use the same probes to examine microorganisms, cells, and mice as they do in patients to visualize and characterize the biology of disease, monitor its progression, and evaluate therapeutic efficacy. Over 4000+ PET probes have been developed to help answer a variety of biological questions, but only the glucose analog [18F]FDG is routinely used for molecular imaging diagnostics in patient care. There is still an unmet need to develop additional probes which can annotate other key aspects of cancer biochemistry, including those in which the diagnostics share common targets with drugs, to truly establish it as a key technology for realizing improved treatment and monitoring in personalized medicine. The clinical translation of next generation PET probes is hampered by a lack of multi-site infrastructure to robustly, reliably, and cost-effectively support their supply to fulfill the initial data generation required to determine safety and efficacy in humans. This is often a key issue in bridging the “gap” between proof-of-concept research and FDA approval; Pharma and Biotech, who face increasing pressure to use diagnostics to develop drugs more efficiently, require significant validation studies and a reliable supply to realize the value of a novel PET probe to their clinical program and invest in future studies. Thus, early clinical studies in this gap are currently relegated to single-site production, or must undergo a cost- and-time-prohibitive assimilation into a commercial radiopharmacy before they've been clinically vetted. To facilitate a paradigm shift in the enablement of novel PET probes for the clinical trial community, a fundamental change in production ideology and infrastructure re-imagining is required. Creating a network of academic radiochemistry cores that standardize and share synthesis, purification, formulation, and quality control protocols through automation and cloud-based applications for clinical production serves to reduce barriers to translating PET probes from the preclinical research environment to first-in-human studies, as well enable rapid dissemination of PET probes across multiple sites to spur and de-risk academic and industry collaboration. The overall goal of this proposal is to establish and deploy a novel, low cost, scalable approach to the clinical translation of a next generation PET probes for cancer, starting with candidate probe [18F]CFA, with potential commercialization as a predictive response biomarker for cancer immunotherapies in solid tumors (i.e. CTLA-4/PD1 blockade), a pharmacodynamic biomarker for dCK inhibitors, and a predictive response biomarker for chemotherapy nucleoside prodrugs.

Public Health Relevance Statement:
PROJECT NARRATIVE To transform the care of cancer patients, novel molecular imaging modalities to measure biochemical and cellular events are needed in personalized medicine. The goal of this proposal is to develop and commercialize molecular imaging markers and novel technologies to predict tumor responses to therapies and target immune system activation.

Project Terms:
Address; Amendment; Assimilations; Automation; Biochemical; Biochemistry; Biological; Biological Process; Biology; Biotechnology; cancer biomarkers; cancer care; cancer diagnosis; Cancer Diagnostics; cancer immunotherapy; Cells; chemotherapy; Clinical; clinical application; Clinical Research; clinical research site; clinical translation; Clinical Trials; Clinical Trials Network; cloud based; Collection; commercialization; Community Trial; computer network; Contracts; cost; Cytotoxic T-Lymphocyte-Associated Protein 4; Data; Deoxycytidine Kinase; design; Detection; Development; Diagnostic; Diagnostic Imaging; Disease; DNA; Documentation; Ensure; Environment; Enzymes; Event; Face; Family; Formulation; Future; Generations; glucose analog; Goals; Human; imaging biomarker; Imaging Device; imaging modality; Immune system; Immune Targeting; improved; Individual; Industry Collaboration; inhibitor/antagonist; Institution; Malignant Neoplasms; manufacturing process; Measures; Medical; microorganism; molecular imaging; Monitor; Multi-Institutional Clinical Trial; Mus; new technology; next generation; novel; Nucleosides; Pathway interactions; Patient Care; Patients; Performance; personalized medicine; Pharmaceutical Preparations; pharmacodynamic biomarker; Pharmacologic Substance; Phase; phase 1 study; Positron-Emission Tomography; pre-clinical research; predicting response; pressure; Prodrugs; Production; programs; Protocols documentation; Quality Control; Radiochemistry; Radiolabeled; Readiness; Reagent; Recurrence; Research; Research Infrastructure; Research Personnel; response; response biomarker; Risk; Safety; Site; Solid Neoplasm; Staging; Standardization; System; Technology; Therapeutic Trials; Time; Training; Training Activity; Translating; Translations; Treatment Efficacy; tumor; Validation; validation studies; Writing