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A Physiological Perspective on the Use of Imaging to Assess the In Vivo Delivery of Therapeutics

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Abstract

Our goal is to provide a physiological perspective on the use of imaging to optimize and monitor the accumulation of nanotherapeutics within target tissues, with an emphasis on evaluating the pharmacokinetics of organic particles. Positron emission tomography (PET), magnetic resonance imaging (MRI) and ultrasound technologies, as well as methods to label nanotherapeutic constructs, have created tremendous opportunities for preclinical optimization of therapeutics and for personalized treatments in challenging disease states. Within the methodology summarized here, the accumulation of the construct is estimated directly from the image intensity. Particle extravasation is then estimated based on classical physiological measures. Specifically, the transport of nanotherapeutics is described using the concept of apparent permeability, which is defined as the net flux of solute across a blood vessel wall per unit surface area of the blood vessel and per unit solute concentration difference across the blood vessel wall. The apparent permeability to small molecule MRI constructs is accurately shown to be far larger than that estimated for proteins such as albumin or nanoconstructs such as liposomes. Further, the quantitative measurements of vascular permeability are shown to facilitate detection of the transition from a pre-malignant to a malignant cancer and to quantify the delivery enhancement resulting from interventions such as ultrasound. While PET-based estimates facilitate quantitative comparisons of many constructs, high field MRI proves useful in the visualization of model drugs within small lesions and in the evaluation of the release and intracellular trafficking of nanoparticles and cargo.

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Acknowledgments

The authors acknowledge the support of NIHR01CA134549, NIHR01CA112356, NIHR01CA103828, T32EB003827 and the National Heart Lung and Blood Institute of the NIH as a Program of Excellence in Nanotechnology award (HHSN268201000043C).

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Authors and Affiliations

  1. Department of Biomedical Engineering, University of California, Davis, Davis, CA, USA

    Shengping Qin, Brett Z. Fite, M. Karen J. Gagnon, Jai W. Seo & Katherine W. Ferrara

  2. Department of Physiology, University of California, Davis, Davis, CA, USA

    Fitz-Roy Curry

  3. The Department of Biomedicine, Molecular Imaging Center, University of Bergen, Bergen, Norway

    Frits Thorsen

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  1. Shengping Qin
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Correspondence to Katherine W. Ferrara.

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Associate Editor Gang Bao oversaw the review of this article.

Shengping Qin and Brett Z. Fite contributed equally to this paper.

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Qin, S., Fite, B.Z., Gagnon, M.K.J. et al. A Physiological Perspective on the Use of Imaging to Assess the In Vivo Delivery of Therapeutics. Ann Biomed Eng 42, 280–298 (2014). https://doi.org/10.1007/s10439-013-0895-2

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