ArticleMolecular imaging and biology2022
Non-invasive Imaging of Antisense Oligonucleotides in the Brain via In Vivo Click Chemistry.
Article in Molecular imaging and biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 20 citations in OpenAlex.
- Oligonucleotides Post-Synthetic Modifications: An Overview of Clickable Nucleoside Phosphoramidites Suitable for Solid-Phase Synthesis.Chembiochem : a European journal of chemical biology · 2026Review
- Central Nervous System Biodistribution and Pharmacokinetics of Radiolabeled Tofersen in Rodents, Nonhuman Primates, and Humans.Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2026Article
- Pretargeted Immuno-PET Enables Monoclonal Antibody Imaging Beyond the Blood-Brain Barrier.Molecular pharmaceutics · 2025Article
- Article
- Head-to-Head Comparison of theMolecular pharmaceutics · 2025Article
- Article
- Trans-cyclooctene-a Swiss army knife for bioorthogonal chemistry: exploring the synthesis, reactivity, and applications in biomedical breakthroughs.EJNMMI radiopharmacy and chemistry · 2024Review
- Imaging-Assisted Antisense Oligonucleotide Delivery for Tumor-Targeted Gene Therapy.Chemical & biomedical imaging · 2024Review
- Nucleic acid drug vectors for diagnosis and treatment of brain diseases.Signal transduction and targeted therapy · 2023Review
Corrections and comments
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Authors and funding
18 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeThe treatment of complex neurological diseases often requires the administration of large therapeutic drugs, such as antisense oligonucleotide (ASO), by lumbar puncture into the intrathecal space in order to bypass the blood-brain barrier. Despite the growing number of ASOs in clinical development, there are still uncertainties regarding their dosing, primarily around their distribution and kinetics in the brain following intrathecal injection. The challenge of taking measurements within the delicate structures of the central nervous system (CNS) necessitates the use of non-invasive nuclear imaging, such as positron emission tomography (PET). Herein, an emergent strategy known as "pretargeted imaging" is applied to image the distribution of an ASO in the brain by developing a novel PET tracer, [ PROCEDURES: A novel small molecule tracer for pretargeted PET imaging of ASOs in the CNS is developed and tested in a series of in vitro and in vivo experiments, including biodistribution in rats and non-human primates.
resultsIn vitro data and extensive in vivo rat data demonstrated delivery of the tracer to the CNS, and its successful ligation to its ASO target in the brain. In an NHP study, the slow tracer kinetics did not allow for specific binding to be determined by PET.
conclusionA CNS-penetrant radioligand for pretargeted imaging was successfully demonstrated in a proof-of-concept study in rats, laying the groundwork for further optimization.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.