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Dynamic microPET imaging of ultrasound contrast agents and lipid delivery.

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 (18)F-labeled lipid ([(18)F]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 approximately 2.6%-injected dose per cubic centimeter (% ID/cc) and the liver demonstrated the largest total accumulation (approximately 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, [(18)F]fluorodipalmitin was used to characterize the biodistribution of contrast microbubble shells and the deposition of lipid was shown to be locally increased after insonation.

SUBMITTER: Tartis MS

PROVIDER: S-EPMC2756153 | biostudies-literature | 2008 Nov

REPOSITORIES: biostudies-literature

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Dynamic microPET imaging of ultrasound contrast agents and lipid delivery.

Tartis Michaelann S MS Kruse Dustin E DE Zheng Hairong H Zhang Hua H Kheirolomoom Azadeh A Marik Jan J Ferrara Katherine W KW

Journal of controlled release : official journal of the Controlled Release Society 20080729 3

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 (18)F-labeled lipid ([(18)F]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 ...[more]

PMID: 18718854

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Project description:SignificanceAn effective contrast agent for concurrent multimodal photoacoustic (PA) and ultrasound (US) imaging must have both high optical absorption and high echogenicity. Integrating a highly absorbing dye into the lipid shell of gas core nanobubbles (NBs) adds PA contrast to existing US contrast agents but may impact agent ultrasonic response.AimWe report on the development and ultrasonic characterization of lipid-shell stabilized C3F8 NBs with integrated Sudan Black (SB) B dye in the shell as dual-modal PA-US contrast agents.ApproachPerfluoropropane NBs stabilized with a lipid shell including increasing concentrations of SB B dye were formulated by amalgamation (SBNBs). Physical properties of SBNBs were characterized using resonant mass measurement, transmission electron microscopy and pendant drop tensiometry. Concentrated bubble solutions were imaged for 8 min to assess signal decay. Diluted bubble solutions were stimulated by a focused transducer to determine the response of individual NBs to long cycle (30 cycle) US. For assessment of simultaneous multimodal contrast, bulk populations of SBNBs were imaged using a PA and US imaging platform.ResultsWe produced high agent yield (∼1011) with a mean diameter of ∼200 to 300 nm depending on SB loading. A 40% decrease in bubble yield was measured for solutions with 0.3 and 0.4 mg / ml SB. The addition of SB to the shell did not substantially affect NB size despite an increase in surface tension by up to 8 mN / m. The bubble decay rate increased after prolonged exposure (8 min) by dyed bubbles in comparison to their undyed counterparts (2.5-fold). SB in bubble shells increased gas exchange across the shell for long cycle US. PA imaging of these agents showed an increase in power (up to 10 dB) with increasing dye.ConclusionsWe added PA contrast function to NBs. The addition of SB increased gas exchange across the NB shell. This has important implications in their use as multimodal agents.

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Dynamic microPET imaging of ultrasound contrast agents and lipid delivery.

Publications

Dynamic microPET imaging of ultrasound contrast agents and lipid delivery.

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