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Pharmacokinetics of Encapsulated Paclitaxel: Multi-Probe Analysis With PET

[+] Author Affiliations
Michaelann S. Tartis, Jan Marik, Rachel E. Pollard, Hua Zhang, Jinyi Qi, Julie L. Sutcliffe, Katherine W. Ferrara

University of California at Davis, Davis, CA

Azadeh Kheirolomoom

University of Calfornia at Davis, Davis, CA

Paper No. SBC2007-176435, pp. 113-114; 2 pages
doi:10.1115/SBC2007-176435
From:
  • ASME 2007 Summer Bioengineering Conference
  • ASME 2007 Summer Bioengineering Conference
  • Keystone, Colorado, USA, June 20–24, 2007
  • Conference Sponsors: Bioengineering Division
  • ISBN: 0-7918-4798-5
  • Copyright © 2007 by ASME

abstract

We have combined two imaging probes and used PET as a means to provide image-based validation for a novel targeted drug delivery system. The first probe was a direct labeling of the drug [18F]fluoropaclitaxel [1–3], which was inserted into various carrier vehicle formulations. The second probe, [18F]fluoro-1,2-dipalmitoyl-sn-glycerol, i.e. [18F]FDP involved radiolabeling the lipid vehicle. Paclitaxel, which is poorly soluble in aqueous media, also has limited solubility and stability in lipophilic environments such as liposomes. Stable association of paclitaxel with the lipid bilayer is affected by a variety of physicochemical factors such as temperature and liposome composition. Paclitaxel crystal formation has been documented, with two forms of solid state within aqueous media and organic solvents, although crystal conformation differs in each media [4,5]. We provide dynamic in vivo image sets providing biodistribution and time activity curves of free [18F]fluoropaclitaxel and liposomal [18F]fluoropaclitaxel as well as free [18F]FDP, liposomal [18F]FDP, and [18F]FDP in an ultrasound contrast agent. Serial studies were performed within a small group of rats, minimizing inter-animal variability. The two labeled molecules have different biodistributions: paclitaxel is rapidly taken up in the liver, intestines and kidneys, while the labeled lipid incorporated into liposomes stays in circulation with minimal uptake in organs other than spleen. Here, we have developed a quantitative method to follow paclitaxel and lipid vehicles to their destination in vivo in order to improve targeted paclitaxel delivery.

Copyright © 2007 by ASME

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