Brendon E. Cook
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Central Nervous System Biodistribution and Pharmacokinetics of Radiolabeled Tofersen in Rodents, Nonhuman Primates, and Humans Open
Antisense oligonucleotides (ASOs) are an important therapeutic modality across several therapeutic areas, offering currently available and potential future treatment options for patients. ASO pharmacokinetics, biodistribution, and regional…
<i>Trans</i>-Cyclooctene Isomerization Catalyzed by Thiamine Degradation Products in Cell Culture Media Open
PET imaging of intrathecally dosed ASO neurology drugs is challenging due to the long time needed to achieve steady-state brain distribution, making the use of a simple 18F tag impossible with its short radioactive half-life. To overcome t…
Quantitative Determination of Click-Reactive Antisense Oligonucleotide and Its Reactivity in Rat Brains by Hybridization LC-MS/MS to Support Pretargeted PET Imaging Open
Antisense oligonucleotide (ASO) therapeutics are rapidly increasing in prevalence for the treatment of neurodegenerative diseases. A novel pretargeted positron emission tomography (PET) imaging methodology based on in vivo click chemistry …
Pretargeted Imaging for In Vivo Assessment of ASO Therapy Delivery in Alzheimer’s Disease Open
Background Intrathecally (IT) delivered antisense oligonucleotides (ASOs) are promising therapies that can reduce tau pathology in Alzheimer’s Disease (AD). However, current plasma and CSF sampling methods to estimate brain tissue exposure…
Pretargeted Imaging for In Vivo Assessment of ASO Therapy Delivery in Alzheimer’s Disease Open
Background Intrathecally (IT) delivered antisense oligonucleotides (ASOs) are promising therapies that can reduce tau pathology in Alzheimer’s Disease (AD). However, current plasma and CSF sampling methods to estimate brain tissue exposure…
View article: Development of a PET Tracer for OGA with Improved Kinetics in the Living Brain
Development of a PET Tracer for OGA with Improved Kinetics in the Living Brain Open
O-GlcNAcylation is thought to play a role in the development of tau pathology in Alzheimer's disease because of its ability to modulate tau's aggregation propensity. O-GlcNAcylation is regulated by 2 enzymes: O-GlcNAc transferase and O-Glc…
Pretargeted PET of Osteodestructive Lesions in Dogs Open
The last decade has witnessed the creation of a highly effective approach to in vivo pretargeting based on the inverse electron demand Diels-Alder (IEDDA) click ligation between tetrazine (Tz) and trans-cyclooctene (TCO). Despite the stead…
Removal of Fc Glycans from [<sup>89</sup>Zr]Zr-DFO-Anti-CD8 Prevents Peripheral Depletion of CD8<sup>+</sup> T Cells Open
The N-linked biantennary glycans on the heavy chain of immunoglobulin G (IgG) antibodies (mAbs) are instrumental in the recognition of the Fc region by Fc-gamma receptors (FcγR). In the case of full-length mAb-based imaging tracers targeti…
Toward the Optimization of Click-Mediated Pretargeted Radioimmunotherapy Open
Pretargeted radioimmunotherapy (PRIT) based on the inverse electron demand Diels-Alder reaction has shown promise in murine models of disease, yet the radiation dosimetry of this approach must be optimized to make it a viable clinical opti…
Pretargeted Radioimmunotherapy Based on the Inverse Electron Demand Diels-Alder Reaction Open
While radioimmunotherapy (RIT) is a promising approach for the treatment of cancer, the long pharmacokinetic half-life of radiolabeled antibodies can result in high radiation doses to healthy tissues. Perhaps not surprisingly, several diff…
A brief overview of metal complexes as nuclear imaging agents Open
In this review, we seek to provide a brief and accessible overview of metal complex-based radiopharmaceuticals for nuclear imaging.
The Development of Novel Platforms for the Imaging of Cancer by Positron Emission Tomography Open
The role of antibody-based imaging of cancer by positron emission tomography (PET) has expanded significantly in recent years and is poised to radically alter the way that cancer is diagnosed and treated. However, one hurdle that remains i…
Pretargeted Imaging and Therapy Open
In vivo pretargeting stands as a promising approach to harnessing the exquisite tumor-targeting properties of antibodies for nuclear imaging and therapy while simultaneously skirting their pharmacokinetic limitations. The core premise of p…
Pretargeted PET Imaging Using a Site-Specifically Labeled Immunoconjugate Open
In recent years, both site-specific bioconjugation techniques and bioorthogonal pretargeting strategies have emerged as exciting technologies with the potential to improve the safety and efficacy of antibody-based nuclear imaging. In the w…