First PET Study with a Benzothiazol Amyloidimaging Agent (PIB) in Alzheimer’s Disease Patients and Healthy Volunteers
Part of the
Research and Perspectives in Alzheimer’s Disease
book series (ALZHEIMER)
Amyloid plaques are a hallmark of Alzheimer’s disease (AD) and have become a therapeutic target, creating a need to quantify plaque deposition in vivo. Recently, benzothiazole-aniline derivatives that bind amyloid-beta protein with high affinity and cross the blood-brain barrier have been developed. These have been characterized by pre-clinical pharmacology and toxicology, resulting in the choice of [N-methyl-11C]2- [4’-(methylamino)-phenyl] 6-hydroxybenzothiazole, [(6-OH-BTA-1) = PIB, according to the Uppsala University code] for the first human study with positron emission tomography (PET).
Nine patients with the clinical diagnosis of AD and five healthy volunteers were examined using a dual tracer protocol consisting of 18F-labelled deoxyglucose (FDG) and PIB. The objective of the study was to determine the distribution of PIB in the brains of AD patients and healthy volunteers and compare this distribution to the cerebral metabolic rate in both groups.
In AD patients, PIB was retained in frontal and temporoparietal association cortices. Low retention was observed in the sensorimotor cortex, the visual cortex, the thalami, the brainstem, the putamen and the cerebellum. In the healthy volunteers, the uptake was very low in every cortical area.
Some correlation between the localization of PIB and the areas of hypometabolism was found in the AD patients. The distribution of PIB in the patients is consistent with the known topology of amyloid plaque deposition in AD brain.
This tracer seems to be a promising human amyloid-imaging agent, which appears to have good specificity for amyloid deposits in vivo. This new approach might have important diagnostic uses and might serve as a surrogate marker for evaluating the efficacy of anti-amyloid therapeutics that are already used in clinical trials.
KeywordsPositron Emission Tomography White Matter Cortical Area Amyloid Plaque Positron Emission Tomography Study
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
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