# Image-guided, intra-arterial delivery of antibodies to the central nervous system

> **NIH NIH R01** · UNIVERSITY OF MARYLAND BALTIMORE · 2021 · $386,250

## Abstract

Central nervous system (CNS) diseases including neurological, oncological and psychiatric conditions
are the biggest healthcare expense worldwide. Biotechnological drugs such as antibodies are a frontline of
therapeutic progress elsewhere in the body, but the CNS diseases rarely benefit from them mostly due blood
brain barrier (BBB) limiting their penetration to the brain, as they have relatively large size. The benefit of
macromolecules mostly comes from higher specificity and safety over traditional small molecule approaches.
 Intra-arterial route of delivery of therapeutic agents to the brain is an intuitive approach and it has been
attempted for years but so far it has been plagued by the variability. We have recently shown that real-time
MRI guidance is capable to overcome these limitations. Moreover, macromolecules such as antibodies can be
far easier tagged and imaged than small molecules in majority of circumstances, which provides a unique
opportunity to be even more precise. Radiolabeling of antibodies can be performed by chelation of radiometals,
which is relatively simple process to be completed even by a biologist, and radionuclides can be easily shipped
from all over the country so no need for on-site cyclotron is needed. We have been first to show the
feasibility of merging technologies of antibody radiolabeling and intra-arterial delivery and observed
impressive benefits of this route of delivery. While, our early results are quite compelling there are still
many puzzles to be put together to better understand the advantages of intra-arterial route as they might be
crucial for a proper design of intra-arterial injections in patients, not only to eradicate variability but also to learn
what are the optimal conditions to take the most of the procedure.
 First, here we will learn how the antibody concentration in cerebral vasculature contributes to their
extravasation as well as we will look into the potential role of plasma-antibody interaction as a factor limiting
extravasation of intravenously administered antibody. This knowledge will provide clear guidelines on a
positioning catheter during intra-arterial infusions in patients, as if high concentration and no exposure of
antibody to blood are contribution factors, then the catheter should be placed quite distally in the cerebral
vessels to maximize the benefit of intra-arterial route. Then, we will learn what is the optimal concentration to
perform procedure safely while to maximize the brain uptake of antibodies. While, the direct numbers will apply
to mice only, it will also give a context to considerations to clinical translation. Then, we will study in detail the
potential impact of antibody delivery to the CNS on essential brain processes through getting insight into
transcriptomics and proteomics to detect potential negative consequences, which would then serve as a basis
for finding countermeasures. Ultimately, we will look into antibody clearance from the brain and the r...

## Key facts

- **NIH application ID:** 10176254
- **Project number:** 1R01NS120929-01
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE
- **Principal Investigator:** Miroslaw Janowski
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $386,250
- **Award type:** 1
- **Project period:** 2021-04-15 → 2026-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10176254

## Citation

> US National Institutes of Health, RePORTER application 10176254, Image-guided, intra-arterial delivery of antibodies to the central nervous system (1R01NS120929-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10176254. Licensed CC0.

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