Suresh Vatakuti - Academia.edu (original) (raw)
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![Research paper thumbnail of Development of [ 18 F]-Labeled Pyrazolo[4,3- e ]-1,2,4- triazolo[1,5- c ]pyrimidine (SCH442416) Analogs for the Imaging of Cerebral Adenosine A 2A Receptors with Positron Emission Tomography](https://attachments.academia-assets.com/40206527/thumbnails/1.jpg)
](Journal of Medicinal Chemistry, 2014
Cerebral adenosine A 2A receptors (A 2A Rs) are attractive therapeutic targets for the treatment ... more Cerebral adenosine A 2A receptors (A 2A Rs) are attractive therapeutic targets for the treatment of neurodegenerative and psychiatric disorders. We developed high affinity and selective compound 8 (SCH442416) analogs as in vivo probes for A 2A Rs using PET. We observed the A 2A R-mediated accumulation of [ 18 F]fluoropropyl ([ 18 F]-10b) and [ 18 F]fluoroethyl ([ 18 F]-10a) derivatives of 8 in the brain. The striatum was clearly visualized in PET and in vitro autoradiography images of control animals and was no longer visible after pretreatment with the A 2A R subtype-selective antagonist KW6002. In vitro and in vivo metabolite analyses indicated the presence of hydrophilic (radio)metabolite(s), which are not expected to cross the blood-brainbarrier. [ 18 F]-10b and [ 18 F]-10a showed comparable striatum-to-cerebellum ratios (4.6 at 25 and 37 min post injection, respectively) and reversible binding in rat brains. We concluded that these compounds performed equally well, but their kinetics were slightly different. These molecules are potential tools for mapping cerebral A 2A Rs with PET.
Toxicology in vitro : an international journal published in association with BIBRA, Jan 6, 2015
In rat in vivo, both paracetamol (APAP) and carbon tetrachloride (CCl4) induce liver necrosis, bu... more In rat in vivo, both paracetamol (APAP) and carbon tetrachloride (CCl4) induce liver necrosis, but long-term treatment with CCl4, in contrast to paracetamol, causes liver fibrosis. The aim of this study was to perform transcriptomic analysis to compare the early changes in mRNA expression profiles induced by APAP and CCl4 in the rat precision-cut liver slice model (PCLS) and to identify early markers that could predict fibrosis-inducing potential. Microarray data of rat PCLS exposed to APAP andCCl4was generated using a toxic dose based on decrease in ATP levels. Toxicity pathway analysis using a custom made fibrosis-related gene list showed fibrosis as one of the predominant toxic endpoints in CCl4-treated, but not in APAP-treated PCLS. Moreover, genes which have a role in fibrosis such as alpha-B crystallin, jun proto-oncogene, mitogen-activated protein kinase 6, serpin peptidase inhibitor and also the transcription factor Kruppel-like-factor-6 were up-regulated by CCl4, but not by...
Journal of Medicinal Chemistry, 2014
Cerebral adenosine A 2A receptors (A 2A Rs) are attractive therapeutic targets for the treatment ... more Cerebral adenosine A 2A receptors (A 2A Rs) are attractive therapeutic targets for the treatment of neurodegenerative and psychiatric disorders. We developed high affinity and selective compound 8 (SCH442416) analogs as in vivo probes for A 2A Rs using PET. We observed the A 2A R-mediated accumulation of [ 18 F]fluoropropyl ([ 18 F]-10b) and [ 18 F]fluoroethyl ([ 18 F]-10a) derivatives of 8 in the brain. The striatum was clearly visualized in PET and in vitro autoradiography images of control animals and was no longer visible after pretreatment with the A 2A R subtype-selective antagonist KW6002. In vitro and in vivo metabolite analyses indicated the presence of hydrophilic (radio)metabolite(s), which are not expected to cross the blood-brainbarrier. [ 18 F]-10b and [ 18 F]-10a showed comparable striatum-to-cerebellum ratios (4.6 at 25 and 37 min post injection, respectively) and reversible binding in rat brains. We concluded that these compounds performed equally well, but their kinetics were slightly different. These molecules are potential tools for mapping cerebral A 2A Rs with PET.
Toxicology in vitro : an international journal published in association with BIBRA, Jan 6, 2015
In rat in vivo, both paracetamol (APAP) and carbon tetrachloride (CCl4) induce liver necrosis, bu... more In rat in vivo, both paracetamol (APAP) and carbon tetrachloride (CCl4) induce liver necrosis, but long-term treatment with CCl4, in contrast to paracetamol, causes liver fibrosis. The aim of this study was to perform transcriptomic analysis to compare the early changes in mRNA expression profiles induced by APAP and CCl4 in the rat precision-cut liver slice model (PCLS) and to identify early markers that could predict fibrosis-inducing potential. Microarray data of rat PCLS exposed to APAP andCCl4was generated using a toxic dose based on decrease in ATP levels. Toxicity pathway analysis using a custom made fibrosis-related gene list showed fibrosis as one of the predominant toxic endpoints in CCl4-treated, but not in APAP-treated PCLS. Moreover, genes which have a role in fibrosis such as alpha-B crystallin, jun proto-oncogene, mitogen-activated protein kinase 6, serpin peptidase inhibitor and also the transcription factor Kruppel-like-factor-6 were up-regulated by CCl4, but not by...