A new in silico approach to revolutionize CNS PET tracer design and enhance translational success
ELSEVIER SCIENCE INC. 2021: S24-S25
View details for Web of Science ID 000652014900035
Use of 55 PET radiotracers under approval of a Radioactive Drug Research Committee (RDRC).
EJNMMI radiopharmacy and chemistry
2020; 5 (1): 24
BACKGROUND: In the US, EU and elsewhere, basic clinical research studies with positron emission tomography (PET) radiotracers that are generally recognized as safe and effective (GRASE) can often be conducted under institutional approval. For example, in the United States, such research is conducted under the oversight of a Radioactive Drug Research Committee (RDRC) as long as certain requirements are met. Firstly, the research must be for basic science and cannot be intended for immediate therapeutic or diagnostic purposes, or to determine the safety and effectiveness of the PET radiotracer. Secondly, the PET radiotracer must be generally recognized as safe and effective. Specifically, the mass dose to be administered must not cause any clinically detectable pharmacological effect in humans, and the radiation dose to be administered must be the smallest dose practical to perform the study and not exceed regulatory dose limits within a 1-year period. In our experience, the main barrier to using a PET radiotracer under RDRC approval is accessing the required information about mass and radioactive dosing.RESULTS: The University of Michigan (UM) has a long history of using PET radiotracers in clinical research studies. Herein we provide dosing information for 55 radiotracers that will enable other PET Centers to use them under the approval of their own RDRC committees.CONCLUSIONS: The data provided herein will streamline future RDRC approval, and facilitate further basic science investigation of 55 PET radiotracers that target functionally relevant biomarkers in high impact disease states.
View details for DOI 10.1186/s41181-020-00110-z
View details for PubMedID 33175263
Neuroinflammation PET imaging: Current opinion and future directions.
Journal of nuclear medicine : official publication, Society of Nuclear Medicine
Neuroinflammation is a pathological hallmark of numerous neurologic diseases. Positron emission tomography (PET) imaging enables a non-invasive means to investigate, quantify, and track the spatiotemporal dynamics of various immune cells in living subjects. Translocator protein 18 kDa (TSPO)-PET is a technique for detecting glial activation that has yielded valuable clinical data linking neuroinflammation to cognitive decline in neurodegenerative diseases and has also been used preliminarily as a therapy monitoring tool. However, considerable limitations of TSPO-PET have prompted identification of other more cell-specific and functionally relevant biomarkers. This review analyzes the clinical potential of available and emerging PET biomarkers of innate and adaptive immune responses, with mention of exciting future directions for the field.
View details for DOI 10.2967/jnumed.119.229443
View details for PubMedID 32620705
Development of a CD19 PET tracer for detecting B cells in a mouse model of multiple sclerosis.
Journal of neuroinflammation
2020; 17 (1): 275
B cells play a central role in multiple sclerosis (MS) through production of injurious antibodies, secretion of pro-inflammatory cytokines, and antigen presentation. The therapeutic success of monoclonal antibodies (mAbs) targeting B cells in some but not all individuals suffering from MS highlights the need for a method to stratify patients and monitor response to treatments in real-time. Herein, we describe the development of the first CD19 positron emission tomography (PET) tracer, and its evaluation in a rodent model of MS, experimental autoimmune encephalomyelitis (EAE).Female C57BL/6?J mice were induced with EAE through immunization with myelin oligodendrocyte glycoprotein (MOG1-125). PET imaging of na´ve and EAE mice was performed 19?h after administration of [64Cu]CD19-mAb. Thereafter, radioactivity in organs of interest was determined by gamma counting, followed by ex vivo autoradiography of central nervous system (CNS) tissues. Anti-CD45R (B220) immunostaining of brain tissue from EAE and na´ve mice was also conducted.Radiolabelling of DOTA-conjugated CD19-mAb with 64Cu was achieved with a radiochemical purity of 99% and molar activity of 2?GBq/?mol. Quantitation of CD19 PET images revealed significantly higher tracer binding in whole brain of EAE compared to na´ve mice (2.02 ▒ 0.092 vs. 1.68 ▒ 0.06 percentage of injected dose per gram, % ID/g, p = 0.0173). PET findings were confirmed by ex vivo gamma counting of perfused brain tissue (0.22 ▒ 0.020 vs. 0.12 ▒ 0.003 % ID/g, p = 0.0010). Moreover, ex vivo autoradiography of brain sections corresponded with PET imaging results and the spatial distribution of B cells observed in B220 immunohistochemistry-providing further evidence that [64Cu]CD19-mAb enables visualization of B cell infiltration into the CNS of EAE mice.CD19-PET imaging can be used to detect elevated levels of B cells in the CNS of EAE mice, and has the potential to impact the way we study, monitor, and treat clinical MS.
View details for DOI 10.1186/s12974-020-01880-8
View details for PubMedID 32948198
Radiolabeling and pre-clinical evaluation of a first-in-class CD19 PET Tracer for imaging B cells in multiple sclerosis
SOC NUCLEAR MEDICINE INC. 2019
View details for Web of Science ID 000473116800129