國家衛生研究院 NHRI:Item 3990099045/11447
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    题名: In Vivo PET/CT neuroimaging of radiolabeled nanocarriers following intranasal drug delivery (INDD): Validation using Ex Vivo PET/CT, gamma counting and autoradiography
    作者: Veronesi, M;Cheng, SH;Zamora, M;Tsai, H;Lo, LW;Yang, CS;Lapi, S;Chen, CT;Vannier, M
    贡献者: Institute of Biomedical Engineering and Nanomedicine
    摘要: Objectives In vivo dual-modality imaging, such as Micro-PET/CT, is promising for preclinical testing of nanoparticle (NP) drug delivery systems, so experiments were done in vivo and ex vivo to validate intranasal drug delivery approach in a rat model. Methods A single application of 100 nm-sized polymer-micellar hybrid nanoparticles (PLA-DSPE-PEG-NPs) tagged with Zirconium 89 (Zr89, half-life = 3.3 days) were delivered either intranasally (IN, N=3) or intravenously (IV, N=3) to a series of anesthetized Sprague Dawley rats. PET/CT images were obtained over 2 hours in vivo and processed using the VivoQuant image analysis software. PET activity was quantitated in brain subregions using a digital Paxinos and Watson plug-in, and standard uptake values (SUVs) were computed for brain regions based on the atlas-based regions-of-interest (ROIs). Following in vivo imaging, select animals were sacrificed and the brains removed and imaged via PET/CT for 24 hours. The olfactory region, brainstem and forebrain regions of several brains were isolated for independent verification of nanoparticle localization using gamma well counting at 1 hr (N=3), 2 hr (N=6), 4 hr (N=3), 6 hr (N=3) and 24 hr (N=3) following INDD or IV administration. The results were tabulated and compared to the ROI SUVs obtained from the corresponding PET scans. For the autoradiography studies, the brains of three animals were isolated at 1 and 2 hr following INDD or IV administration and cut using a brain matrix into 1 mm sagittal sections. The brain sections were exposed to an autoradiographic film and compared to the PET/CT and gamma well counting studies. Results In vivo PET/CT imaging demonstrated uptake and transport of PLA-DSPE-PEG NPs into the brain as much as 35-fold higher after INDD as compared to IV administration. Brain subregional activity was validated ex vivo by observing the highest activity in the olfactory region and brain stem as observed with in vivo imaging. Quantitation of brain activity compared to nasal cavity activity ex vivo indicated 0.3% brain uptake compared to the initial administered dose. In a similar pattern, to the PET results, the gamma well counting studies demonstrated increased uptake in the olfactory regions and brainstem to a much greater degree than the forebrain structures at early time points. The autoradiography results demonstrate increased activity in the olfactory region, trigeminal nerves and their downstream target in the brainstem pons region, thus providing a third independent method of validation for nose-brain delivery. Conclusions The results indicate that micro-PET/CT may provide a quantitative, localized and in vivo means to determine the temporal and spatial distribution of drugs/nanocarriers after intranasal delivery. There is a critical and immediate need for better evaluation of drug delivery to the central nervous system, especially through the intranasal route. INDD of radio-nanoparticle drug delivery systems evaluated using in vivo microimaging and validated ex vivo using PET/CT, gamma well counting and autoradiography may significantly impact the emerging field of radio-nanotheranostics.
    日期: 2016-05
    關聯: Journal of Nuclear Medicine. 2016 May;57(Suppl. 2):Meeting Abstract 2705a.
    Link to: http://jnm.snmjournals.org/content/57/supplement_2/2705a.abstract
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0161-5505&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000442211003255
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