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Article

Pharmacokinetics of Single Domain Antibodies and Conjugated Nanoparticles Using a Hybrid near Infrared Method

1
Laboratory of Functional and Molecular Imaging, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA
2
Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, MI 63130, USA
3
Center for Neuroscience and Regenerative Medicine, Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD 20892, USA
4
Department of Neurology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Manuela Malatesta
Int. J. Mol. Sci. 2021, 22(16), 8695; https://doi.org/10.3390/ijms22168695
Received: 29 June 2021 / Revised: 5 August 2021 / Accepted: 9 August 2021 / Published: 13 August 2021
(This article belongs to the Special Issue Molecular Imaging in Nanomedical Research 2.0)
Iron oxide nanoparticles and single domain antibodies from camelids (VHHs) have been increasingly recognized for their potential uses for medical diagnosis and treatment. However, there have been relatively few detailed characterizations of their pharmacokinetics (PK). The aim of this study was to develop imaging methods and pharmacokinetic models to aid the future development of a novel family of brain MRI molecular contrast agents. An efficient near-infrared (NIR) imaging method was established to monitor VHH and VHH conjugated nanoparticle kinetics in mice using a hybrid approach: kinetics in blood were assessed by direct sampling, and kinetics in kidney, liver, and brain were assessed by serial in vivo NIR imaging. These studies were performed under “basal” circumstances in which the VHH constructs and VHH-conjugated nanoparticles do not substantially interact with targets nor cross the blood brain barrier. Using this approach, we constructed a five-compartment PK model that fits the data well for single VHHs, engineered VHH trimers, and iron oxide nanoparticles conjugated to VHH trimers. The establishment of the feasibility of these methods lays a foundation for future PK studies of candidate brain MRI molecular contrast agents. View Full-Text
Keywords: VHH; nanoparticles; near-infrared imaging; biodistribution; pharmacokinetic modeling VHH; nanoparticles; near-infrared imaging; biodistribution; pharmacokinetic modeling
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MDPI and ACS Style

Su, S.; Esparza, T.J.; Nguyen, D.; Mastrogiacomo, S.; Kim, J.H.; Brody, D.L. Pharmacokinetics of Single Domain Antibodies and Conjugated Nanoparticles Using a Hybrid near Infrared Method. Int. J. Mol. Sci. 2021, 22, 8695. https://doi.org/10.3390/ijms22168695

AMA Style

Su S, Esparza TJ, Nguyen D, Mastrogiacomo S, Kim JH, Brody DL. Pharmacokinetics of Single Domain Antibodies and Conjugated Nanoparticles Using a Hybrid near Infrared Method. International Journal of Molecular Sciences. 2021; 22(16):8695. https://doi.org/10.3390/ijms22168695

Chicago/Turabian Style

Su, Shiran, Thomas J. Esparza, Duong Nguyen, Simone Mastrogiacomo, Joong H. Kim, and David L. Brody 2021. "Pharmacokinetics of Single Domain Antibodies and Conjugated Nanoparticles Using a Hybrid near Infrared Method" International Journal of Molecular Sciences 22, no. 16: 8695. https://doi.org/10.3390/ijms22168695

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