Improving availability of ImmunoPET via automation of radio-synthesis and quality control of antibody-based HIV imaging PET tracers on a single platform.

ImmunoPET Imaging allows visualization of biological processes in the body via radiolabeled monoclonal antibodies (mAb’s) with Positron Emission Tomography (PET). ImmunoPET has proven to be a groundbreaking innovation yielding actionable medical information that is not otherwise obtainable in many disease areas. However, ImmunoPET imaging is only available at select academic centers limited by complexity of production of short-lived Zr-89-radiolabeled antibodies., which prevents access of ImmunoPET to the majority of patient population and to clinical trial utilization. To address this barrier, Trace-Ability will develop Tracer-ONE – compact and affordable automation of the entire [Zr- 89]mAb production procedure including radio-labeling, QC and immunoassay with results available before the PET scan. Production staff will need only to install a kit, add the radionuclide, initiate the process and return to collect the product along with QC report. Such solution will enable any facility with limited staff and budget to start producing ImmunoPET tracers in a scalable, standardized, safe and GMP-compliant manner. Key new capabilities needed for Tracer-ONE have been demonstrated in Phase I including radiolabeling, immunoreactivity assay and most QC tests. Phase II is designed to deliver a fully-functional system suitable for cGMP production of a variety ImmunoPET tracers for clinical use. To maximize the immediate impacts of the project, we chose the HIV application of ImmunoPET, currently limited to a single location in the US. To demonstrate the scalability of Tracer-ONE, we will sequentially enable two HIV ImmunoPET tracers starting with [Zr-89]VRC01. Specific Aim 1 Develop fully automated [Zr-89]VRC01 radio-synthesis starting with [Zr-89]oxalate and a disposable kit and yielding [Zr-89]VRC01 that meets all requirements for clinical use. Specific Aim 2 Develop fully automated [Zr- 89]VRC01 quality control including immunoreactivity. The deliverable of this aim is to design a disposable kit and corresponding protocol to enable all measurements required prior to clinical use of [Zr-89]VRC01. Specific Aim 3 Optimize Tracer-ONE for fully automated production of [Zr-89]VRC01 for clinical use. The ultimate deliverable of this aim is acceptance of the system’s performance by UCSF quality and regulatory groups. Specific Aim 4 Demonstrate efficient expansion of established Tracer-ONE capabilities to another HIV ImmunoPET tracer. The deliverable of this aim is a fully automated radiosynthesis and QC process on Tracer-ONE qualified for a second HIV tracer at UCSF and meeting the same acceptance criteria as [Zr-89]VRC01. The outcome of the project is principal enablement of a capability that does not exist today – routine ImmunoPET tracer production across a diverse range of products leading to broad availability of ImmunoPET imaging to American patients in AIDS, cancer, arthritis and other disease areas. In additional to diagnostic value, broad availability of ImmunoPET will increase the effectiveness of clinical trials and availability of new therapies and the percentage of patients that respond to therapies.