A physiological perspective on the use of imaging to assess the in vivo delivery of therapeutics

Shengping Qin, Brett Z. Fite, M. Karen J Gagnon, Jai Seo, Fitz Roy Curry, Frits Thorsen, Katherine W. Ferrara

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)280-298
Number of pages19
JournalAnnals of Biomedical Engineering
Volume42
Issue number2
DOIs
StatePublished - 2014

Keywords

  • Delivery of therapeutics
  • Nanotherapeutic constructs
  • Pharmacokinetics
  • Quantitative imaging

ASJC Scopus subject areas

  • Biomedical Engineering

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