PET imaging of distinct brain uptake of a nanobody and similarly-sized PAMAM dendrimers after intra-arterial administration

Lesniak, Wojciech G.; Chu, Chengyan; Jabłońska, Anna; Azad, Babak Behnam; Zwaenepoel, Olivier; Zawadzki, Michał; Lisok, Ala; Pomper, Martin G.; Walczak, Piotr; Gettemans, Jan; Janowski, Mirosław

doi:10.1007/s00259-019-04347-y

Cited by 35 publications

(29 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Osmotic disruption has been applied to the anti-gelsolin VHH Nb11 [ 65 ] designed for the potential treatment of hereditary gelsolin amyloidosis, an autosomal dominantly inherited amyloid disorder. PET imaging showed that mannitol BBB opening allowed an increase of the VHH in the brain of around 2.5-fold, however the VHH was injected intraarterially [ 66 ]. This mode of administration has already demonstrated an advantage over intravenous administration regarding brain exposure [ 67 ].…”

Section: Single-domain Antibodies Crossing the Blood–brain Barriermentioning

confidence: 99%

“…A nanobody directed against vascular endothelium growth factor (VEGF) has shown a BBB passage optimized by mannitol treatment and intra-arterial administration instead of intravenous injection. The improved brain uptake allowed imaging of the brain by positron electron tomography (PET) using 89 Zr as radioactive tracer [ 66 ].…”

Section: Single-domain Antibodies Crossing the Blood–brain Barriermentioning

confidence: 99%

See 1 more Smart Citation

Brain Delivery of Single-Domain Antibodies: A Focus on VHH and VNAR

2020

View full text Add to dashboard Cite

Passive immunotherapy, i.e., treatment with therapeutic antibodies, has been increasingly used over the last decade in several diseases such as cancers or inflammation. However, these proteins have some limitations that single-domain antibodies could potentially solve. One of the main issues of conventional antibodies is their limited brain penetration because of the blood–brain barrier (BBB). In this review, we aim at exploring the different options single-domain antibodies (sDAbs) such as variable domain of heavy-chain antibodies (VHHs) and variable new antigen receptors (VNARs) have already taken to reach the brain allowing them to be used as therapeutic, diagnosis or transporter tools.

show abstract

Section: Single-domain Antibodies Crossing the Blood–brain Barriermentioning

confidence: 99%

Section: Single-domain Antibodies Crossing the Blood–brain Barriermentioning

confidence: 99%

Brain Delivery of Single-Domain Antibodies: A Focus on VHH and VNAR

2020

View full text Add to dashboard Cite

show abstract

“…Furthermore, PET allowing whole body quantitative imaging demonstrated a distinct advantage of intra‐arterial delivery over the intravenous route for drug accumulation in the brain (Lesniak et al, 2018; Lesniak et al, 2019). Therefore, integrating such imaging methodology into EV studies is highly promising and is expected to boost the development of precision medicine.…”

Section: Discussionmentioning

confidence: 99%

Imaging as a tool to accelerate the translation of extracellular vesicle‐based therapies for central nervous system diseases

Gao

Chu

Jabłońska

et al. 2020

WIREs Nanomed Nanobiotechnol

Self Cite

View full text Add to dashboard Cite

Extracellular vesicles (EVs) are natural and diverse lipid bilayer‐enclosed particles originating from various cellular components and containing an abundance of cargoes. Due to their unique properties, EVs have gained considerable interest as therapeutic agents for a variety of diseases, including central nervous system (CNS) disorders. Their therapeutic value depends on cell origin but can be further enhanced by enrichment of cargo when used as drug carriers. Therefore, there has been significant effort directed toward introducing them to clinical practice. However, it is essential to avoid the failures we have seen with whole‐cell therapy, in particular for the treatment of the CNS. Successful launching of clinical studies is contingent upon the understanding of the biodistribution of EVs, including their uptake and clearance from organs and specific homing into the region of interest. A multitude of noninvasive imaging methods has been explored in vitro to investigate the spatio‐temporal dynamics of EVs administered in vivo. However, only a few studies have been performed to track the delivery of EVs, especially delivery to the brain, which is the most therapeutically challenging organ. We focus here on the use of advanced imaging techniques as an essential tool to facilitate the acceleration of clinical translation of EV‐based therapeutics, especially in the CNS arena. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Neurological Disease Diagnostic Tools > in vivo Nanodiagnostics and Imaging

show abstract

“…By combining IA administration with BBB opening, >10 times higher monoclonal antibody delivery to the brain could be obtained. A follow-up study using 89 Zr-labeled polyamidoamine dendrimers showed only a marginal improvement of brain delivery upon IA administration combined with BBB opening, while the similar approach for 89 Zr-labeled nanobodies showed a 2.5-fold increase of brain uptake [149]. The results of Lesniak et al, indicating the advantage of IA administration, are in line with the results of the previously discussed PET imaging studies using [ 177 Lu]Lu-DOTA-TATE in patients with grade II meningioma [108,109].…”

Section: Final Considerations and Future Directionmentioning

confidence: 99%

The Added Value of Diagnostic and Theranostic PET Imaging for the Treatment of CNS Tumors

Pruis

Dongen

Zanten

2020

IJMS

View full text Add to dashboard Cite

This review highlights the added value of PET imaging in Central Nervous System (CNS) tumors, which is a tool that has rapidly evolved from a merely diagnostic setting to multimodal molecular diagnostics and the guidance of targeted therapy. PET is the method of choice for studying target expression and target binding behind the assumedly intact blood–brain barrier. Today, a variety of diagnostic PET tracers can be used for the primary staging of CNS tumors and to determine the effect of therapy. Additionally, theranostic PET tracers are increasingly used in the context of pharmaceutical and radiopharmaceutical drug development and application. In this approach, a single targeted drug is used for PET diagnosis, upon the coupling of a PET radionuclide, as well as for targeted (nuclide) therapy. Theranostic PET tracers have the potential to serve as a non-invasive whole body navigator in the selection of the most effective drug candidates and their most optimal dose and administration route, together with the potential to serve as a predictive biomarker in the selection of patients who are most likely to benefit from treatment. PET imaging supports the transition from trial and error medicine to predictive, preventive, and personalized medicine, hopefully leading to improved quality of life for patients and more cost-effective care.

show abstract

PET imaging of distinct brain uptake of a nanobody and similarly-sized PAMAM dendrimers after intra-arterial administration

Cited by 35 publications

References 32 publications

Brain Delivery of Single-Domain Antibodies: A Focus on VHH and VNAR

Brain Delivery of Single-Domain Antibodies: A Focus on VHH and VNAR

Imaging as a tool to accelerate the translation of extracellular vesicle‐based therapies for central nervous system diseases

The Added Value of Diagnostic and Theranostic PET Imaging for the Treatment of CNS Tumors

Contact Info

Product

Resources

About