Tuesday, November 6, 2012

Positron Emission Tomography Imaging of Amyloid Senile Plaques and Neurofibrillary Tangles

      Several groups have been developing new, small-molecule probes to image the amyloid NPs and NFTs.        
     Current methods for measuring brain amyloid, such as histochemical stains, require tissue fixation on postmortem or biopsy material. Available in vivo methods for measuring NPs or NFTs are indirect. Studies that may lead to direct in vivo, human AP imaging include various radiolabeled probes using small organic and organometallic molecules capable of detecting differences in amyloid-fibril structure or amyloid-protein sequences. Investigators also have used chrysamine-G, a carboxylic acid analogue of Congo red, an amyloid-staining histologic dye, serum amyloid-P component, a normal plasma  glycoprotein that binds to amyloid-deposit fibrils (Lovat, O'Brien, Armstrong, et al., 1998), or monoclonal antibodies (Majocha et al, 1992).
      Methodological difficulties that hinder progress with these techniques include poor blood-brain barrier crossing and limited specificity and sensitivity. In addition, most approaches do not measure both NPs and NFTs. Recently, Barrio et al. (1999) reported using a hydrophobic, radiofluorinated derivative of l,l-dicyano-2-[6-(dimethylamino)naphthalen-2-yllpropene (FDDNP) (Jacobson, Petric, Hogenkamp, Sinur, & Barrio,1996) with PET to measure the cerebral localization and load of NFTs and SPs in AD patients. The probe showed visualization of NFTs, NPs, and diffuse amyloid in AD brain specimens using in vitro fluorescence microscropy, which matched results using conventional stains (e.g., thioflavin S) in the same tissue specimens. Such approaches may ultimately aid in the early detection of AD and brain-function monitoring during antidementia treatment trials, particularly those designed to interrupt accumulation of NPs and NFTs.

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