Positron emission tomography (PET) is a type of nuclear medicine procedure that measures metabolic activity of the cells of body tissues. PET is actually a combination of nuclear medicine and biochemical analysis. PET is most often used by oncologists (specializing in cancer treatment), neurologists and neurosurgeons (specializing in treatment and surgery of the brain and nervous system), and cardiologists (specializing in the treatment of the heart). However, as advances in PET technologies continue, this procedure is beginning to be used more widely in other areas. Since PET is a type of nuclear medicine procedure, this means that a tiny amount of a radioactive substance, called a radiopharmaceutical (radionuclide or radioactive tracer), is used during the procedure to assist in the examination of the tissue under study.
Recently researchers from the International Center for Biomedicine and the University of Chile and Center for Bioinformatics of the Universidad de Talca, have found that two benzimidazole derivative drugs may be suitable for use as PET radiotracers and enable imaging for the early detection of Alzheimer’s Disease. Neurofibrillary tangles are pathological protein aggretages found within neurons in cases of Alzheimer’s disease. Tangles are formed by the hyperphosphorylation of microtubule-associated protein tau. Tau proteins stabilize microtubules. They are abundant in neurons in the Central Nervous System. When tau proteins are defective, it no longer stabilize microtubules properly and thus results in alzheimer’s disease. The two benzimidazole derivatives lanzoprazole and astemizole, exclusively spot the pathological oligomers of tau protein. According to the team, since the neurofibrillary tangles are absolutely linked with cognitive impairment, these drugs presents immense potential in PET neuroimaging for the early detection of AD and also lessen the formation of NFTs.
The present study is based on sophisticated proteomics and databases of molecular interactions. It is astonishing that the new study may help to find potential new drug targets for the early for early diagnosis and treatment of Alzheimer´s disease. These two drugs has already been approved for treatment of proton pump disorders and as an antihistamine respectively, specifically bind directly to aggregated variants of tau protein, paired helical filaments (PHFs) and NFTs in Alzheimer´s brains.
The team examined the interactions of lanzoprazole and astemizole with the anomalous tau aggregates by various classical radioligand assays combined with surface plasmon resonance, bioinformatic approaches and immunofluorescence studies on isolated PHFs and brain samples from Alzheimer’s cases. Invitro studies using parallel artificial memebrane permeability assays and invivo pazrmacokinetics studies, the capacity of all these drugs to penetrate the blood-brain barrier was confirmed.Dr. Maccioni and Dr. Rojo suggest that “This important discovery will provide the stepping stone for the development of new specific neuroimaging technologies based on PET radiotracers that monitor the formation and growth of NFTs in patients during the course of their lives.”