Delivery of dopamine transporter tracer (PE2I) through blood brain barrier with ultrasound and microbubbles

Autor: Serriere, Sophie, Escoffre, Jaen-Michel, Bodard, Sylvie, Novel, Anthony, Novell, Anthony, Vergote, Jackie, Vercouillie, Johnny, Thiéry, Jean-Claude, CHALON, Sylvie, Bouakaz, Ayache
Přispěvatelé: Imagerie et cerveau (iBrain - Inserm U1253 - UNIV Tours ), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiologie de la reproduction et des comportements [Nouzilly] (PRC), Institut National de la Recherche Agronomique (INRA)-Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), Int Soc Therapeut Ultrasound, Amer Inst Ultrasound Med, Focused Ultrasound Fdn, Philips, Imason SAS, Verason Inc, InSightec Ltd, EyeTechCare, SuperSon Imagine SA, Image Guided Therapy, Elect & Innovat Ltd, Onda Corp, Son Concepts Inc, GE, American Institute of Physics. Melville, USA., Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Recherche Agronomique (INRA)-Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours-Centre National de la Recherche Scientifique (CNRS)
Jazyk: angličtina
Rok vydání: 2011
Předmět:
Zdroj: AIP Conference Proceedings
11. International Symposium on Therapeutic Ultrasound
11. International Symposium on Therapeutic Ultrasound, American Institute of Physics. Melville, USA., Apr 2011, New York, United States. ⟨10.1063/1.4757355⟩
DOI: 10.1063/1.4757355⟩
Popis: The blood-brain barrier plays a major role in controlling the delivery of therapeutic and imaging agents to the brain. The aim of this study was to investigate the use of ultrasound and microbubbles to increase its delivery through the BBB and by determining the optimal experimental conditions that achieve a transient and safe BBB disruption. First, we established the ultrasound conditions that achieved a transient BBB disruption in rats using a non-permeant marker, Evans blue. Hence SonoVue® (450 μL/kg) and Evans blue (100 mg/kg) were intravenously administered. BBB leakage was obtained using ultrasound insonation through the rat skull at 1.6 MPa, PRF 1 Hz, duty cycle 12%, burst 10 ms during 120 sec. BBB disruption was observed in all treated animals (N=4) by histological analysis. The same experimental conditions were applied to enhance brain uptake of PE2I. Biological samples were analyzed using a scintillation counter apparatus. The results showed 50% and 20% increase of 125I-PE2I uptake in the striatum and cerebral cortex, respectively, in the treated rats (N=5) versus control (N=4). Similar enhancements were observed using SonoVue® at half concentration. This innovative method provides a great potential for intracerebral delivery of molecular ligands that could be used for the therapy of brain diseases.The blood-brain barrier plays a major role in controlling the delivery of therapeutic and imaging agents to the brain. The aim of this study was to investigate the use of ultrasound and microbubbles to increase its delivery through the BBB and by determining the optimal experimental conditions that achieve a transient and safe BBB disruption. First, we established the ultrasound conditions that achieved a transient BBB disruption in rats using a non-permeant marker, Evans blue. Hence SonoVue® (450 μL/kg) and Evans blue (100 mg/kg) were intravenously administered. BBB leakage was obtained using ultrasound insonation through the rat skull at 1.6 MPa, PRF 1 Hz, duty cycle 12%, burst 10 ms during 120 sec. BBB disruption was observed in all treated animals (N=4) by histological analysis. The same experimental conditions were applied to enhance brain uptake of PE2I. Biological samples were analyzed using a scintillation counter apparatus. The results showed 50% and 20% increase of 125I-PE2I uptake in the striat...
Databáze: OpenAIRE
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