Biomedical subjects

Chester A Mathis

Publications and source records attributed to Chester A Mathis.

42 records · Page 3Linked to original sources

PubMed2002

A lipophilic thioflavin-T derivative for positron emission tomography (PET) imaging of amyloid in brain.

The synthesis of a new lipophilic thioflavin-T analogue (2-[4' -(methylamino)phenyl]benzothiazole, 6) with high affinity for amyloid is reported. Intravenous injection of [(11)C]-labeled 6 in control mice resulted in high brain uptake. Amyloid deposits were imaged with multiphoton microscopy in the brains of living transgenic mice following the systemic injection of unlabeled 6. [(11)C]6 is a promising amyloid imaging agent for Alzheimer's disease.

Alzheimer Disease↗

PubMed2002

Evidence of increased serotonin-1A receptor binding in type 2 diabetes: a positron emission tomography study.

Animal studies have shown diabetes-induced changes in the state and function of the serotonin neuroreceptor system. Diabetes also has induced structural and functional alterations in hippocampus and been associated with altered hypothalamopituitary adrenal axis regulation. In this study, serotonin-1A (5-HT(1A)) receptor binding was measured in humans with type 2 diabetes (n=6) and healthy controls (n=6), using positron emission tomography (PET) and [carbonyl-11C]WAY 100635. Significantly greater 5-HT(1A) receptor binding was detected in mesial temporal cortex, including hippocampus (P<0.05) for type 2 subjects (relative to controls). Within the type 2 group, glycosylated hemoglobin and stressed plasma cortisol levels were positively correlated (P<0.02). These findings support previous studies that suggest serotonergic underpinnings to the neurobiology of diabetes and have shown diabetes-induced neurological changes in hippocampus.

Adult↗

PubMed2002

Imaging Abeta plaques in living transgenic mice with multiphoton microscopy and methoxy-X04, a systemically administered Congo red derivative.

The identification of amyloid deposits in living Alzheimer disease (AD) patients is important for both early diagnosis and for monitoring the efficacy of newly developed anti-amyloid therapies. Methoxy-X04 is a derivative of Congo red and Chrysamine-G that contains no acid groups and is therefore smaller and much more lipophilic than Congo red or Chrysamine-G. Methoxy-X04 retains in vitro binding affinity for amyloid beta (Abeta) fibrils (Ki = 26.8 nM) very similar to that of Chrysamine-G (Ki = 25.3 nM). Methoxy-X04 is fluorescent and stains plaques, tangles, and cerebrovascular amyloid in postmortem sections of AD brain with good specificity. Using multiphoton microscopy to obtain high-resolution (1 microm) fluorescent images from the brains of living PSI/APP mice, individual plaques could be distinguished within 30 to 60 min after a single i.v. injection of 5 to 10 mg/kg methoxy-X04. A single i.p. injection of 10 mg/kg methoxy-X04 also produced high contrast images of plaques and cerebrovascular amyloid in PSI/APP mouse brain. Complementary quantitative studies using tracer doses of carbon- 11-labeled methoxy-X04 show that it enters rat brain in amounts that suggest it is a viable candidate as a positron emission tomography (PET) amyloid-imaging agent for in vivo human studies.

Alkenes↗

PubMed2002

Imaging amyloid-beta deposits in vivo.

Alzheimer disease (AD) is an illness that can only be diagnosed with certainty with postmortem examination of brain tissue. Tissue samples from afflicted patients show neuronal loss, neurofibrillary tangles (NFTs), and amyloid-beta plaques. An imaging technique that permitted in vivo detection of NFTs or amyloid-beta plaques would be extremely valuable. For example, chronic imaging of senile plaques would provide a readout of the efficacy of experimental therapeutics aimed at removing these neuropathologic lesions. This review discusses the available techniques for imaging amyloid-beta deposits in the intact brain, including magnetic resonance imaging, positron emission tomography, single photon emission computed tomography, and multiphoton microscopy. A variety of agents that target amyloid-beta deposits specifically have been developed using one or several of these imaging modalities. The difficulty in developing these tools lies in the need for the agents to cross the blood-brain barrier while recognizing amyloid-beta with high sensitivity and specificity. This review describes the progress in developing reagents suitable for in vivo imaging of senile plaques.

Amyloid beta-Peptides↗

PubMed2002

Sequential H(2)(15)O PET studies in baboons: before and after amphetamine.

UNLABELLED: PET and (11)C-raclopride have been used to assess dopamine activity in vivo using a paradigm that involved d-amphetamine (AMPH)-induced endogenous dopamine release that led to reductions (relative to baseline) in the (11)C-raclopride-specific binding parameter (binding potential). A common assumption in bolus injection PET studies of this type is that cerebral blood flow (CBF) does not vary during the scan. The goal of this work was to examine the effect of AMPH administration on sequential PET measures of CBF. METHODS: Eight dynamic H(2)(15)O PET scans were acquired with arterial blood sampling in 6 baboons: 4 scans before AMPH (over 60 min) and 4 scans after AMPH (over 60 min) (0.6 mg/kg AMPH). Magnetic resonance images (coregistered to PET) were used to define regions of interest that included cortex, striatum (including subregions), and cerebellum. Data were analyzed using a 1-tissue compartment model. CBF was assessed through K(1) (mL/mL/min). RESULTS: Temporal patterns of the CBF alterations were similar across regions for each baboon. For 5 of 6 baboons, a general pattern of an initial increase in K(1) was observed after AMPH that gradually declined toward baseline, after minimizing anesthesia-induced variability in the in vivo measures. Although these alterations after AMPH were statistically significant in particular subcortical regions and cerebellum, such changes would not likely influence measures of (11)C-raclopride binding potential to a significant extent. CONCLUSION: These data support previous PET studies for which constant blood flow was assumed during the bolus PET (11)C-raclopride/AMPH experiment across striatal subregions, while underscoring the importance of considering effects of anesthesia when interpreting in vivo imaging parameters.

Anesthesia↗

PubMedDate not supplied

Synthesis and evaluation of 2-(3'-iodo-4'-aminophenyl)-6-hydroxybenzothiazole for in vivo quantitation of amyloid deposits in Alzheimer's disease.

A potent and brain permeable amyloid ligand has been identified as a lead compound capable of I-123/125-labelling for single photon emission computed tomography (SPECT) imaging. In this study, we report the synthesis and I-125-radiolabelling of Compound 6 and its in vitro and in vivo properties. Compound 6 [2-(3'-iodo-4'-aminophenyl)-6-hydroxybenzothiazole] bound to synthetic A beta(1-40) fibrils in a saturable manner, exhibiting an affinity (Ki) of 11+/-1.1 nM in a competitive binding assay using a tritiated thioflavin T analog ([3H]BTA-1) as radioligand. [125I]6 binding to synthetic A beta(1-40) fibrils fit a single-site model. [125I]6 exhibited several-fold higher binding to homogenates of frontal cortex from post-mortem Alzheimer's disease brain relative to age-matched control brain homogenates. No difference in binding was observed in cerebellum. The ratio of radioactivity concentration between frontal cortex and cerebellum was 6-fold higher in AD brain homogenates than the age-matched control. [125I]6 also readily penetrated the blood-brain barrier in normal control mice with an average radioactivity concentration of 6.43+/-0.62%ID/g detected in the whole brain at 2 min post i.v. injection. At 30 min, the radioactivity concentration decreased to 0.40+/-0.05%ID/g, indicating good clearance in the absence of amyloid deposits in the brain.

Alzheimer Disease↗