The COVID-19 Rapid Cure Task Force (RCTF), a collaboration between TRACER and the Medical Imaging Center (MIC) at the University Medical Center Groningen, is offering the global community unique access to immediately generate in-human data on a potential COVID-19 treatment or vaccine by providing expertise, infrastructure and capacity. The goal is to accelerate the drug development of COVID-19 treatments and vaccines, which are urgently needed and studied by multiple R&D groups around the world.
Facilities and expertise to accelerate COVID-19 vaccine or treatment.
In order to accelerate drug development for treatment and prevention of COVID-19 infections, Rapid Cure Task Force assures the highest priority for COVID-19 research projects. TRACER and the MIC have made the following facilities and expertise available:
- GMP facilities for the labeling of drugs with radionuclides (fluorine-18, gallium-68, zirconium-89 etc.) and fluorescent dyes (IRDye800 and others)
- In vivo and ex vivo fluorescence equipment: open air fluorescence cameras (SurgVision Explorer Air, Novodac Spy), endoscopy (dedicated clinical fluorescent endoscopy / bronchoscopy / confocal laser endomicroscopy) and ex vivo imaging equipment (LICOR PEARL, Odyssey flatbed scanner and fluorescence microscopy in the 800nm range)
- PET imaging facility with PET/CT and digital PET/CT scanner, dedicated technologists and nuclear medicine physicians.
- Staffing and priority time slots to conduct imaging in patients
- Guidance and expertise by world renowned scientists from academia and industry
Labeling of RNA based pharmaceuticals.
The COVID-19 pandemic emerged many pharmaceutical companies to rapidly develop novel drugs and vaccines for treatment and prevention of COVID-19. Many of these drugs and vaccines are RNA-based. In addition, some of these pharmaceuticals have entered phase I clinical trials. Given the fast spread of the virus and the severe symptoms of the disease, it is of high importance to meticulously study the binding capacities of the drug to the virus/affected tissue and not to healthy tissue. A high “on-target” binding combined with low “off-target” binding is a prerequisite for a potent COVID-19 drug with a low risk for side effects. Similarly, mRNA vaccines need to be studied in terms of biodistribution (i.e. lymphoid tissue – spleen localization) and pharmacokinetics after for instance intramuscular injection of the vaccine by whole body imaging techniques like PET/CT.
Therefore, RCTF proposes to use in vivo molecular imaging in COVID-19 patients to evaluate the on- and off-target binding of the novel drugs and vaccine biodistribution to select promising candidates for further clinical evaluation. By using previously described labeling strategies of mRNA with a chelator-radiometal complex (eg. gallium-68, aluminum-fluoride-18, zirconium-89) or a near-infrared fluorescent dye (IRDye800CW) we will be able to study the whole body biodistribution and pharmacokinetics by PET and specific targeting at the cellular level by fluorescence imaging (in vivo and ex vivo on biopsies). By using a dual-labeling approach (Lindsay et al. Nature Biomedical Engineering, 2019), the strengths of both imaging modalities are combined.
Labeling of monoclonal antibodies.
Similarly to RNA-based pharmaceuticals, antibodies can be labeled with radionuclides and fluorescent dyes for molecular imaging of drug targeting. TRACER has a long-standing track record in the labeling of monoclonal antibodies with the NIR dye IRDye800CW and consecutive clinical in vivo and ex vivo imaging in oncology. TRACER has a standardized imaging protocol for in vivo and ex vivo imaging. This allows for the correlation of the fluorescent signal with tumor cells (Koller et al. Nature Communications 2018). With this fluorescence imaging technology, we will also be able to evaluate the targeting properties of antibody-based COVID-19 drugs.
Antibodies labeled with zirconium-89 are frequently used in clinical trials for PET imaging of treatment response in oncology. Several studies with 89Zr-labeled mAb’s have been conducted at the University Medical Center Groningen (UMCG). For example, treatment response monitoring of immune-checkpoint inhibitors (Bensch et al. Nature Medicine, 2019). Furthermore, 89Zr-labeling of antibody-based COVID-19 drugs would enable the selection of highly promising antibody-based candidates for further clinical evaluation.
Treatment and imaging of COVID-19 patients with hydroxychloroquine.
Recently it was claimed that the anti-malaria drugs chloroquine would have beneficial effect on COVID-19 infection and the further spread of the virus (Touret et al Antiviral Research, 2020). This prompted health care providers to explore this drug for COVID-19 treatment. While some successful cases were presented in the media, these were mostly case reports. Thus, extensive and standardized characterization is needed. Since chloroquine has fluorescent properties by itself, the chloroquine delivery to the affected tissue can be studied. With this imaging strategy the binding specificity can be studied to predict whether chloroquine has potential to treat COVID-19 infections. Prof. Frijlink, a PharmD at UMCG is working on a novel delivery strategy of the compound in patients with COVID-19.
