Biomedical subjects

Alexandre Coimbra

Publications and source records attributed to Alexandre Coimbra.

3 recordsLinked to original sources

PubMed2006

The role of MRI and PET/SPECT in Alzheimer's disease.

Alzheimer's disease (AD) is difficult to diagnose in its early stages, and even if detected early, there is no preventative treatment. Imaging modalities such as MRI, PET, and SPECT have the potential to contribute to both the diagnosis of Alzheimer's disease, as well as assist in the search for more effective treatments. A number of AD-related biomarkers have been proposed and evaluated. The use of PET imaging to detect alterations in regional brain metabolism using [(18)F]FDG has enabled more sensitive and accurate early diagnosis of AD, especially in conjunction with traditional medical evaluation. Additionally, magnetic resonance imaging and spectroscopy provide a wide range of biomarkers that have been shown to correlate with the progression of AD. Some of these markers have been pursued in clinical trials. Progress has been made toward the evaluation of other more AD-specific biomarkers. However, many questions remain concerning the validity and sensitivity of these imaging biomarkers to aid in the assessment of potential new treatments, especially those related to increased levels of amyloid peptides in the brain.

Alzheimer Disease↗

PubMedDate not supplied

Visualization and quantification of neurokinin-1 (NK1) receptors in the human brain.

PURPOSE: This study was conducted to develop a new positron emission tomography (PET) method to visualize neurokinin-1 (NK(1)) receptor systems in the human brain in vivo in order to examine their neuroanatomical distribution and facilitate investigations of the role of substance P, NK(1) receptors, and NK(1) receptor antagonists in central nervous system (CNS) function and dysfunction. METHODS: PET studies were conducted in 10 healthy male volunteers using a novel selective, high-affinity NK(1) receptor antagonist labeled with fluorine-18 to very high specific radioactivity (up to 2000 GBq/micromol) [F-18]SPA-RQ. Data were collected in 3D mode for greatest sensitivity. Different modeling methods were compared and regional receptor distributions determined for comparison with in vitro autoradiographic studies using postmortem human brain slices with [F-18]SPA-RQ. RESULTS: The studies showed that the highest uptake of [F-18]SPA-RQ was observed in the caudate and putamen. Lower binding was found in globus pallidus and substantia nigra. [F-18]SPA-RQ uptake was also widespread throughout the neocortex and limbic cortex including amygdala and hippocampus. There was very low specific uptake of the tracer in the cerebellar cortex. The distribution pattern was confirmed using in vitro receptor autoradiography with [F-18]SPA-RQ on postmortem human brain slices. Kinetic modeling of the [F-18]SPA-RQ uptake data indicated a binding potential between 4 and 5 in the basal ganglia and between 1.5 and 2.5 in the cortical regions. CONCLUSIONS: [F-18]SPA-RQ is a novel tool for exploration of the functions of NK(1) receptors in man. [F-18]SPA-RQ can be used to define receptor pharmacodynamics and focus dose selection of novel NK(1) receptor antagonists in clinical trials thereby ensuring adequate proof of concept testing particularly in therapeutic applications related to CNS dysfunction.

Adult↗

PubMedDate not supplied

Image-derived input function for [11C]flumazenil kinetic analysis in human brain.

PURPOSE: We describe a method for analysis of [11C]flumazenil data using an input curve directly derived from the positron emission tomography (PET) images. PROCEDURE: The shape of the tracer plasma curve was obtained from the product of the intact flumazenil fraction in plasma in six arterial samples and the internal carotid artery time-activity curve (TAC). The resulting curve was calibrated using the [11C]flumazenil concentration in three of the six samples. The curve peak was recovered by adding an exponential function to the scaled curve whose parameters were estimated from simultaneous fittings of several tissue TACs assuming that all regions share the same input. RESULTS: Good agreement was found between the image-derived and the experimental plasma curves in six subjects. Distribution volumes were highly correlated with linear regression slope and intercept values between [0.94, 1.03] and [-0.10, 0.16], respectively. CONCLUSION: The proposed method is suitable for benzodiazepine receptor quantification requiring only a few blood samples.

Brain↗