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2. Quantitative Imaging of Regional Cerebral Protein Synthesis in Clinical Alzheimer's Disease by [11C]Leucine PET.

Author

Herholz, Karl, McMahon, Adam, Thompson, Jennifer C., Jones, Matthew, Boutin, Herve, Gregory, Jamil, Parker, Christine A., and Hinz, Rainer

Subjects
POSITRON emission tomography, PROTEIN synthesis, ALZHEIMER'S disease, ALZHEIMER'S patients, MEDIAN (Mathematics)
Abstract

Purpose: Protein synthesis is essential to maintain integrity and function of the human brain, and protein synthesis is associated specifically with the formation of long-term memory. Experimental and clinical observations indicate that this process is disturbed in Alzheimer's dementia and other neurodegenerative diseases. In-vivo investigation with positron emission tomography (PET) using [11C]leucine provides a unique possibility to measure regional cerebral protein synthesis (rCPS) rates in human brain and to determine whether it is altered in Alzheimer's disease (AD), and thus may provide a target for future therapeutic interventions. Procedures: In this first human study, we measured rCPS by [11C]leucine PET in four patients with AD (age 57–73 years) and compared the results with six healthy controls (three of whom were age matched and the other three were young controls). Quantification of rCPS also required measurement of amino acid (AA) levels and of free and protein-bound [11C]leucine in plasma during the 90 min PET scans conducted following at least six hours of fasting. Results: Rates of rCPS measured in absolute units of nmol/g/min ranged between 1.81 and 2.53 in AD patients, 2.10 and 2.54 in matched controls, and 2.21 to 2.35 in the young controls. Mean and median values did not show significant differences between the groups. Rates of rCPS also depended upon whether corrections for plasma AA levels were included in the calculations. When considering regional values relative to the corpus callosum as a reference region, there was a tendency towards impairment of rCPS in patients, which was most prominent in the parietal cortex, but did not reach significance. Similar findings were observed with normalisation of rCPS to global cortical mean. Conclusions: In summary, this first human study assessing regional protein synthesis with [11C]leucine in AD has demonstrated where the sources of variance in measurements of cerebral protein synthesis may arise, along with the potential magnitude of this variance. This study also indicates that there is a tendency towards impairment of rCPS in patients with Alzheimer's disease, which requires further investigation including possible partial volume effects due to atrophy. [ABSTRACT FROM AUTHOR]

Published
2024
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3. Supplementary Figure 3 from [18F]-FLT Positron Emission Tomography Can Be Used to Image the Response of Sensitive Tumors to PI3-Kinase Inhibition with the Novel Agent GDC-0941

Author

Cawthorne, Christopher, primary, Burrows, Natalie, primary, Gieling, Roben G., primary, Morrow, Christopher J., primary, Forster, Duncan, primary, Gregory, Jamil, primary, Radigois, Marc, primary, Smigova, Alison, primary, Babur, Muhammad, primary, Simpson, Kathryn, primary, Hodgkinson, Cassandra, primary, Brown, Gavin, primary, McMahon, Adam, primary, Dive, Caroline, primary, Hiscock, Duncan, primary, Wilson, Ian, primary, and Williams, Kaye J., primary

Published
2023
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4. Supplementary Figure 4 from [18F]-FLT Positron Emission Tomography Can Be Used to Image the Response of Sensitive Tumors to PI3-Kinase Inhibition with the Novel Agent GDC-0941

Author

Cawthorne, Christopher, primary, Burrows, Natalie, primary, Gieling, Roben G., primary, Morrow, Christopher J., primary, Forster, Duncan, primary, Gregory, Jamil, primary, Radigois, Marc, primary, Smigova, Alison, primary, Babur, Muhammad, primary, Simpson, Kathryn, primary, Hodgkinson, Cassandra, primary, Brown, Gavin, primary, McMahon, Adam, primary, Dive, Caroline, primary, Hiscock, Duncan, primary, Wilson, Ian, primary, and Williams, Kaye J., primary

Published
2023
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5. Supplementary Figure 1 from [18F]-FLT Positron Emission Tomography Can Be Used to Image the Response of Sensitive Tumors to PI3-Kinase Inhibition with the Novel Agent GDC-0941

Author

Cawthorne, Christopher, primary, Burrows, Natalie, primary, Gieling, Roben G., primary, Morrow, Christopher J., primary, Forster, Duncan, primary, Gregory, Jamil, primary, Radigois, Marc, primary, Smigova, Alison, primary, Babur, Muhammad, primary, Simpson, Kathryn, primary, Hodgkinson, Cassandra, primary, Brown, Gavin, primary, McMahon, Adam, primary, Dive, Caroline, primary, Hiscock, Duncan, primary, Wilson, Ian, primary, and Williams, Kaye J., primary

Published
2023
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6. Data from [18F]-FLT Positron Emission Tomography Can Be Used to Image the Response of Sensitive Tumors to PI3-Kinase Inhibition with the Novel Agent GDC-0941

Author

Cawthorne, Christopher, primary, Burrows, Natalie, primary, Gieling, Roben G., primary, Morrow, Christopher J., primary, Forster, Duncan, primary, Gregory, Jamil, primary, Radigois, Marc, primary, Smigova, Alison, primary, Babur, Muhammad, primary, Simpson, Kathryn, primary, Hodgkinson, Cassandra, primary, Brown, Gavin, primary, McMahon, Adam, primary, Dive, Caroline, primary, Hiscock, Duncan, primary, Wilson, Ian, primary, and Williams, Kaye J., primary

Published
2023
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7. Supplementary Figure 2 from [18F]-FLT Positron Emission Tomography Can Be Used to Image the Response of Sensitive Tumors to PI3-Kinase Inhibition with the Novel Agent GDC-0941

Author

Cawthorne, Christopher, primary, Burrows, Natalie, primary, Gieling, Roben G., primary, Morrow, Christopher J., primary, Forster, Duncan, primary, Gregory, Jamil, primary, Radigois, Marc, primary, Smigova, Alison, primary, Babur, Muhammad, primary, Simpson, Kathryn, primary, Hodgkinson, Cassandra, primary, Brown, Gavin, primary, McMahon, Adam, primary, Dive, Caroline, primary, Hiscock, Duncan, primary, Wilson, Ian, primary, and Williams, Kaye J., primary

Published
2023
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8. Supplementary Figure Legends from [18F]-FLT Positron Emission Tomography Can Be Used to Image the Response of Sensitive Tumors to PI3-Kinase Inhibition with the Novel Agent GDC-0941

Author

Cawthorne, Christopher, primary, Burrows, Natalie, primary, Gieling, Roben G., primary, Morrow, Christopher J., primary, Forster, Duncan, primary, Gregory, Jamil, primary, Radigois, Marc, primary, Smigova, Alison, primary, Babur, Muhammad, primary, Simpson, Kathryn, primary, Hodgkinson, Cassandra, primary, Brown, Gavin, primary, McMahon, Adam, primary, Dive, Caroline, primary, Hiscock, Duncan, primary, Wilson, Ian, primary, and Williams, Kaye J., primary

Published
2023
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9. [18F]-FLT Positron Emission Tomography Can Be Used to Image the Response of Sensitive Tumors to PI3-Kinase Inhibition with the Novel Agent GDC-0941

Author

Cawthorne, Christopher, primary, Burrows, Natalie, additional, Gieling, Roben G., additional, Morrow, Christopher J., additional, Forster, Duncan, additional, Gregory, Jamil, additional, Radigois, Marc, additional, Smigova, Alison, additional, Babur, Muhammad, additional, Simpson, Kathryn, additional, Hodgkinson, Cassandra, additional, Brown, Gavin, additional, McMahon, Adam, additional, Dive, Caroline, additional, Hiscock, Duncan, additional, Wilson, Ian, additional, and Williams, Kaye J., additional

Published
2013
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