These novel compounds and chelation strategies detect tumors with better in vivo stability and production safety than current clinical standards.
Currently, 18F-fluorodeoxyglucose (FDG) is the only radiotracer FDA-approved for routine clinical use in diagnosing and measuring therapeutic response in cancer patients. While positron emission tomography (PET) imaging has proven quite valuable in diagnosing cancers compared to other diagnostic platforms, FDG can detect only a limited number of cancer types and cannot accurately detect metastases, which are primary prognostic indicators.
Advancements in PET imaging have identified Zirconium-89 (89Zr) as a better candidate than FDG for the development of targeted radiotracers due to its favorable half-life of 78.4 hours – which matches that of molecular targeting antibodies. 89Zr has been tested in many clinical trials since the early 2000s. Unfortunately, the standard chelate for 89Zr is unstable and has restricted the clinical development of 89Zr because the radioisotope accumulates in bone and liver of patients, making it unsafe for routine clinical use. In addition, current production of 89Zr -based radiotracers requires highly toxic precursor materials during its preparation, which increases exposure risks to personnel.
Radiochemists at Wake Forest Baptist Medical Center have developed novel chelation strategies and compositions for 89Zr radiotracer development that are stable and safe.
These scientists have developed and validated new methods and compositions for 89Zr-immuno-PET agents with Herceptin in a murine model of HER2+ lung cancer. The resulting compositions have demonstrated high stability superior to FDG in vivo.
- Safer manufacturing: Reagents in these novel production methods reduce exposure risks for manufacturers
- Reduced development risk: These novel compounds are comprised of clinically tested molecules
- Enhanced stability: Inventors have demonstrated stability using novel formulations of compositions previously described as unstable
- Favorable decay characteristics: 89Zr has a significantly longer half-life which matches targeting antibodies used for molecular imaging, and improves patient access to nuclear medicine by increasing the distribution radius
- Targeted and sensitive detection: PET imaging improves accuracy of cancer staging in a cost-effective manner
- Improved stability in vivo: >50% decreased radionuclide accumulation in bone and liver
- Improved sensitivity to detecting metastatic disease
- Applicable to many cancer types and diseases due to the nature of antibodies
Oncology: staging, monitoring therapeutic response, monitoring recurrence; cardiology; infectious disease; neuro-imaging in aging
Stage of Development
- Successfully synthesized and characterized 89Zr-DOTA and generated a crystal structure using single crystal x-ray diffraction (Chemical Science, 2016)
- Successfully tested the performance and biodistribution of 89Zr-DOTA in head-to-head comparison against 89Zr-DFO using micro-PET/CT (Chemical Science, 2016)
- Studies complete in head-to-head comparison of novel chelation strategies. Manuscript in preparation.
- Evaluating performance of 89Zr-DOTA-mAb in head-to-head comparison against 89Zr-DFO-mAb using micro-PET/CT. Manuscript in preparation.
Thaddeus J. Wadas, PhD
Radiology and Cancer Biology
Darpan Pandya, PhD
Nikunj Bhatt, PhD
Nuclear medicine, radiopharmacy, radiology, imaging, positron emission tomography (PET), immuno-PET, oncology
PCT application filed.
Peter Golikov, MBA
Reference #: 15-56