P2‐063: Near‐infrared fluorescence imaging in transgenic mouse models of Alzheimer's disease
Year: 2008
Type: article
Abstract: Molecular diagnostic strategies for detecting and tracking Alzheimer's disease have focused on amyloid-beta (A-Beta), the protein that characteristically accumulates and aggregates to form plaques in the AD brain. A non-invasive imaging technique for amyloid would accelerate pre-clinical drug trials, aid basic AD research in mouse models, and might be translated to the clinic. Some groups have recently demonstrated MRI and PET techniques for imaging amyloid. We are developing near-infrared fluorescence (NIRF) technology for quantitative imaging of amyloid deposits. NIRF imaging uses a molecular beacon approach: NIR fluorophores are injected intravenously, bind a target of interest, and emit photons for detection. In comparison to other modalities, NIRF imaging is low-cost and simple to implement, making it ideal for high-throughput drug discovery and basic research in animal models. Amyloid imaging requires probes that target aggregates with high specificity, emit in the near-infrared spectrum (700–950 nm), and have good brain bioavailability. We screened 30+ commercial NIR fluorophores for amyloid imaging capabilities using tissue staining, fluorescence spectroscopy, and IV injection in transgenic mice. In parallel, we have built a simple NIRF tomography system that allows non-invasive measurement of fluorophores deep within the mouse. The tomography system consists of a laser source, fluorescence filters, a CCD camera, and a 3D camera for boundary detection. We used this system to quantify plaque burden in transgenic mice (B6C3 tg+ APPswe PS1E9) using AOI987, an amyloid-targeting fluorophore [1]. Of the probes tested, 13 exhibited amyloid-binding to plaques in tissue sections from APP mouse brains. Some probes also had fluorescence lifetime and spectral changes when incubated with synthetic A-Beta aggregates, which might enhance amyloid detection. One of the dyes was detected on post-mortem tissue sections following IV administration, suggesting in vivo viability. NIRF imaging is a simple and inexpensive technology for non-invasively monitoring amyloid aggregates. We have identified promising NIRF imaging probes from commercially available fluorophores and plan to use these candidate structures as starting-points for designing probes with higher amyloid-specificity and brain uptake. We have built a NIRF tomography system for imaging these fluorophores in vivo. [1] Hintersteiner et al, Nat Biotechnol. 2005, 23(5):577–83.
Source: Alzheimer s & Dementia
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2055040110