Christopher Kobylecki1, Tobias Langheinrich1, Rainer Hinz2, Emma R L C Vardy3, Gavin Brown2, María-Elena Martino4, Cathleen Haense5, Anna M Richardson6, Alexander Gerhard1, Jose M Anton-Rodriguez2, Julie S Snowden1, David Neary1, Michael J Pontecorvo7, Karl Herholz8. 1. Institute of Brain, Behaviour and Mental Health, University of Manchester, Manchester, United Kingdom Cerebral Function Unit, Greater Manchester Neurosciences Centre, Salford Royal NHS Foundation Trust, Salford, United Kingdom. 2. Institute of Brain, Behaviour and Mental Health, University of Manchester, Manchester, United Kingdom. 3. Institute of Brain, Behaviour and Mental Health, University of Manchester, Manchester, United Kingdom Institute of Neuroscience and Newcastle University Institute of Ageing, Newcastle University, Newcastle upon Tyne, United Kingdom Department of Older Peoples Medicine, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, United Kingdom. 4. Institute of Brain, Behaviour and Mental Health, University of Manchester, Manchester, United Kingdom Unidad de Medicina y Cirugía Experimental, Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain. 5. Department of Nuclear Medicine, Hannover Medical School, Hannover, Germany. 6. Cerebral Function Unit, Greater Manchester Neurosciences Centre, Salford Royal NHS Foundation Trust, Salford, United Kingdom Manchester Medical School, University of Manchester, Manchester, United Kingdom; and. 7. Avid Radiopharmaceuticals, Philadelphia, Pennsylvania. 8. Institute of Brain, Behaviour and Mental Health, University of Manchester, Manchester, United Kingdom karl.herholz@manchester.ac.uk.
Abstract
UNLABELLED: Pathologic deposition of amyloid β (Aβ) protein is a key component in the pathogenesis of Alzheimer disease (AD) but not a feature of frontotemporal dementia (FTD). PET ligands for Aβ protein are increasingly used in diagnosis and research of dementia syndromes. Here, we report a PET study using (18)F-florbetapir in healthy controls and patients with AD and FTD. METHODS: Ten healthy controls (mean age ± SD, 62.5 ± 5.2 y), 10 AD patients (mean age ± SD, 62.6 ± 4.5), and 8 FTD patients (mean age ± SD, 62.5 ± 9.6) were recruited to the study. All patients underwent detailed clinical and neuropsychologic assessment and T1-weighted MR imaging and were genotyped for apolipoprotein E status. All participants underwent dynamic (18)F-florbetapir PET on a high-resolution research tomograph, and FTD patients also underwent (18)F-FDG PET scans. Standardized uptake value ratios (SUVRs) were extracted for predefined gray and white matter regions of interest using cerebellar gray matter as a reference region. Static PET images were evaluated by trained raters masked to clinical status and regional analysis. RESULTS: Total cortical gray matter (18)F-florbetapir uptake values were significantly higher in AD patients (median SUVR, 1.73) than FTD patients (SUVR, 1.13, P = 0.002) and controls (SUVR, 1.26, P = 0.04). (18)F-Florbetapir uptake was also higher in AD patients than FTD patients and controls in the frontal, parietal, occipital, and cingulate cortices and in the central subcortical regions. Only 1 FTD patient (homozygous for apolipoprotein E ε4) displayed high cortical (18)F-florbetapir retention, whereas (18)F-FDG PET demonstrated mesiofrontal hypometabolism consistent with the clinical diagnosis of FTD. Most visual raters classified 1 control (10%) and 8 AD (80%) and 2 FTD (25%) patients as amyloid-positive, whereas ratings were tied in another 2 FTD patients and 1 healthy control. CONCLUSION: Cortical (18)F-florbetapir uptake is low in most FTD patients, providing good discrimination from AD. However, visual rating of FTD scans was challenging, with a higher rate of discordance between interpreters than in AD and control subjects.
UNLABELLED: Pathologic deposition of amyloid β (Aβ) protein is a key component in the pathogenesis of Alzheimer disease (AD) but not a feature of frontotemporal dementia (FTD). PET ligands for Aβ protein are increasingly used in diagnosis and research of dementia syndromes. Here, we report a PET study using (18)F-florbetapir in healthy controls and patients with AD and FTD. METHODS: Ten healthy controls (mean age ± SD, 62.5 ± 5.2 y), 10 ADpatients (mean age ± SD, 62.6 ± 4.5), and 8 FTDpatients (mean age ± SD, 62.5 ± 9.6) were recruited to the study. All patients underwent detailed clinical and neuropsychologic assessment and T1-weighted MR imaging and were genotyped for apolipoprotein E status. All participants underwent dynamic (18)F-florbetapir PET on a high-resolution research tomograph, and FTDpatients also underwent (18)F-FDG PET scans. Standardized uptake value ratios (SUVRs) were extracted for predefined gray and white matter regions of interest using cerebellar gray matter as a reference region. Static PET images were evaluated by trained raters masked to clinical status and regional analysis. RESULTS: Total cortical gray matter (18)F-florbetapir uptake values were significantly higher in ADpatients (median SUVR, 1.73) than FTDpatients (SUVR, 1.13, P = 0.002) and controls (SUVR, 1.26, P = 0.04). (18)F-Florbetapir uptake was also higher in ADpatients than FTDpatients and controls in the frontal, parietal, occipital, and cingulate cortices and in the central subcortical regions. Only 1 FTDpatient (homozygous for apolipoprotein E ε4) displayed high cortical (18)F-florbetapir retention, whereas (18)F-FDG PET demonstrated mesiofrontal hypometabolism consistent with the clinical diagnosis of FTD. Most visual raters classified 1 control (10%) and 8 AD (80%) and 2 FTD (25%) patients as amyloid-positive, whereas ratings were tied in another 2 FTDpatients and 1 healthy control. CONCLUSION: Cortical (18)F-florbetapir uptake is low in most FTDpatients, providing good discrimination from AD. However, visual rating of FTD scans was challenging, with a higher rate of discordance between interpreters than in AD and control subjects.
Authors: Michael J Pontecorvo; Anupa K Arora; Marybeth Devine; Ming Lu; Nick Galante; Andrew Siderowf; Catherine Devadanam; Abhinay D Joshi; Stephen L Heun; Brian F Teske; Stephen P Truocchio; Michael Krautkramer; Michael D Devous; Mark A Mintun Journal: Eur J Nucl Med Mol Imaging Date: 2017-01-07 Impact factor: 9.236
Authors: Antoine Leuzy; Kerstin Heurling; Susan De Santi; Santiago Bullich; Oskar Hansson; Johan Lilja Journal: Am J Nucl Med Mol Imaging Date: 2020-08-25
Authors: Christopher Breault; Jonathan Piper; Abhinay D Joshi; Sara D Pirozzi; Aaron S Nelson; Ming Lu; Michael J Pontecorvo; Mark A Mintun; Michael D Devous Journal: Am J Nucl Med Mol Imaging Date: 2017-07-15