Fiandaca Massimo S, Varenika Vanja, Eberling Jamie, McKnight Tracy, Bringas John, Pivirotto Phillip, Beyer Janine, Hadaczek Piotr, Bowers William, Park John, Federoff Howard, Forsayeth John, Bankiewicz Krystof S
Department of Neurological Surgery, University of California San Francisco, 1855 Folsom Street, Room 226, San Francisco, CA 94103, USA.
Neuroimage. 2009 Aug;47 Suppl 2(Suppl 2):T27-35. doi: 10.1016/j.neuroimage.2008.11.012. Epub 2008 Nov 27.
We are developing a method for real-time magnetic resonance imaging (MRI) visualization of convection-enhanced delivery (CED) of adeno-associated viral vectors (AAV) to the primate brain. By including gadolinium-loaded liposomes (GDL) with AAV, we can track the convective movement of viral particles by continuous monitoring of distribution of surrogate GDL. In order to validate this approach, we infused two AAV (AAV1-GFP and AAV2-hAADC) into three different regions of non-human primate brain (corona radiata, putamen, and thalamus). The procedure was tolerated well by all three animals in the study. The distribution of GFP determined by immunohistochemistry in both brain regions correlated closely with distribution of GDL determined by MRI. Co-distribution was weaker with AAV2-hAADC, although in vivo PET scanning with FMT for AADC activity correlated well with immunohistochemistry of AADC. Although this is a relatively small study, it appears that AAV1 correlates better with MRI-monitored delivery than does AAV2. It seems likely that the difference in distribution may be due to differences in tissue specificity of the two serotypes.
我们正在开发一种用于实时磁共振成像（MRI）可视化腺相关病毒载体（AAV）向灵长类动物大脑进行对流增强递送（CED）的方法。通过将载钆脂质体（GDL）与AAV一起使用，我们可以通过持续监测替代GDL的分布来追踪病毒颗粒的对流运动。为了验证这种方法，我们将两种AAV（AAV1-GFP和AAV2-hAADC）注入非人类灵长类动物大脑的三个不同区域（放射冠、壳核和丘脑）。研究中的三只动物对该操作耐受性良好。通过免疫组织化学确定的两个脑区中GFP的分布与通过MRI确定的GDL的分布密切相关。AAV2-hAADC的共分布较弱，尽管使用FMT进行的AADC活性的体内PET扫描与AADC的免疫组织化学相关性良好。尽管这是一项相对较小的研究，但似乎AAV1与MRI监测的递送的相关性比AAV2更好。分布差异可能是由于两种血清型的组织特异性不同所致。
