Dynamic microPET imaging of ultrasound contrast agents and lipid delivery

Michaelann S. Tartis, Dustin E. Kruse, Hairong Zheng, Hua Zhang, Azadeh Kheirolomoom, Jan Marik, Katherine W. Ferrara

Research output: Contribution to journalArticle

62 Scopus citations

Abstract

Interest in ultrasound contrast agents (lipid-shelled microbubbles) as delivery vehicles is increasing; however, the biodistribution of these agents remains uncharacterized, both with and without ultrasound. In this study, an 18F-labeled lipid ([18F]fluorodipalmitin), incorporated in microbubble shells, was used as a dynamic microPET probe for quantitative 90-minute biodistribution measurements in male Fischer 344 rats (n = 2). The spleen retained the highest concentration of radioactive lipid at ~ 2.6%-injected dose per cubic centimeter (% ID/cc) and the liver demonstrated the largest total accumulation (~ 17% ID). The microbubble pharmacokinetic profile differed from free lipid, which is rapidly cleared from blood, and liposomes, which remain in circulation. Additionally, region of interest (ROI) analysis over 60 minutes (post-ultrasound treatment) quantified the delivery of lipid by therapeutic ultrasound from microbubbles to kidney tissue (n = 8). The ultrasound sequence consisted of a 200 kPa, 5.3 MHz radiation force pulse followed by a 1.6 MPa, 1.4 MHz fragmentation pulse and was applied to one kidney, while the contralateral kidney served as a control. ROI-estimated activity in treated kidneys was slightly but significantly greater at 0 and 60 min than in untreated kidneys (p = 0.0012 and 0.0035, respectively). This effect increased with the number of microbubbles injected (p = 0.006). In summary, [18F]fluorodipalmitin was used to characterize the biodistribution of contrast microbubble shells and the deposition of lipid was shown to be locally increased after insonation.

Original languageEnglish (US)
Pages (from-to)160-166
Number of pages7
JournalJournal of Controlled Release
Volume131
Issue number3
DOIs
StatePublished - Nov 12 2008

Keywords

  • [F]fluorodipalmitin ([F]FDP)
  • MicroPET
  • Targeted drug delivery
  • Therapeutic ultrasound
  • Ultrasound contrast agents

ASJC Scopus subject areas

  • Pharmaceutical Science

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  • Cite this

    Tartis, M. S., Kruse, D. E., Zheng, H., Zhang, H., Kheirolomoom, A., Marik, J., & Ferrara, K. W. (2008). Dynamic microPET imaging of ultrasound contrast agents and lipid delivery. Journal of Controlled Release, 131(3), 160-166. https://doi.org/10.1016/j.jconrel.2008.07.030