Sonia Lavisse1, Daniel García-Lorenzo2, Marie-Anne Peyronneau3, Benedetta Bodini4, Claire Thiriez5, Bertrand Kuhnast3, Claude Comtat3, Philippe Remy6, Bruno Stankoff2, Michel Bottlaender7. 1. CEA-DSV-I2BM, MIRCen, Fontenay-aux-Roses, France CNRS-UMR9199, Universités Paris-Sud and Paris-Saclay, Fontenay-aux-Roses, France sonia.lavisse@cea.fr. 2. Institut du Cerveau et de la Moelle épinière, Inserm-U1127 and Sorbonne University, UPMC-UMRS-1127, Paris, France CNRS-UMR7225, Paris, France. 3. CEA-DSV-I2BM, SHFJ and IMIV, UMR1023 Inserm/CEA/Paris-Sud University, Orsay, France. 4. Institut du Cerveau et de la Moelle épinière, Inserm-U1127 and Sorbonne University, UPMC-UMRS-1127, Paris, France CNRS-UMR7225, Paris, France CEA-DSV-I2BM, SHFJ and IMIV, UMR1023 Inserm/CEA/Paris-Sud University, Orsay, France Department of Neuroimaging, Institute of Psychiatry, King's College London, London, England. 5. CEA-DSV-I2BM, MIRCen, Fontenay-aux-Roses, France CNRS-UMR9199, Universités Paris-Sud and Paris-Saclay, Fontenay-aux-Roses, France Neurology Department, Centre Expert Parkinson, CHU Henri Mondor, AP-HP, Créteil, France. 6. CEA-DSV-I2BM, MIRCen, Fontenay-aux-Roses, France CNRS-UMR9199, Universités Paris-Sud and Paris-Saclay, Fontenay-aux-Roses, France Neurology Department, Centre Expert Parkinson, CHU Henri Mondor, AP-HP, Créteil, France Paris-Est University, Créteil, France; and. 7. CEA-DSV-I2BM, SHFJ and IMIV, UMR1023 Inserm/CEA/Paris-Sud University, Orsay, France CEA-DSV-I2BM, Neurospin, Gif-sur-Yvette, France.
Abstract
UNLABELLED: Translocator protein (TSPO) is expressed at a low level in healthy brain and is upregulated during inflammatory processes that may occur in neurodegenerative diseases. Thus, TSPO may be a suitable in vivo indicator of neurodegeneration. Here, we quantified the (18)F-DPA-714 radioligand in healthy TSPO-genotyped volunteers and developed a method to eliminate the need for invasive arterial blood sampling. METHODS: Ten controls (7 high-affinity binders [HABs] and 3 mixed-affinity binders [MABs]) underwent (18)F-DPA-714 PET with arterial and venous sampling. (18)F-DPA-714 binding was quantified with a metabolite-corrected arterial plasma input function, using the 1- and 2-tissue-compartment models (TCMs) as well as the Logan analysis to estimate total volume distribution (V(T)) in the regions of interest. Alternative quantification methods were tested, including tissue-to-plasma ratio or population-based input function approaches normalized by late time points of arterial or venous samples. RESULTS: The distribution pattern of (18)F-DPA-714 was consistent with the known distribution of TSPO in humans, with the thalamus displaying the highest binding and the cerebellum the lowest. The 2-TCM best described the regional kinetics of (18)F-DPA-714 in the brain, with good identifiability (percentage coefficient of variation < 5%). For each region of interest, V(T) was 47.6% ± 6.3% higher in HABs than in MABs, and estimates from the 2-TCM and the Logan analyses were highly correlated. Equilibrium was reached at 60 min after injection. V(T) calculated with alternative methods using arterial samples was strongly and significantly correlated with that calculated by the 2-TCM. Replacement of arterial with venous sampling in these methods led to a significant but lower correlation. CONCLUSION: Genotyping of subjects is a prerequisite for a reliable quantification of (18)F-DPA-714 PET images. The 2-TCM and the Logan analyses are accurate methods to estimate (18)F-DPA-714 V(T) in the human brain of both HAB and MAB individuals. Population-based input function and tissue-to-plasma ratio with a single arterial sample are promising alternatives to classic arterial plasma input function. Substitution with venous samples is promising but still requires methodologic improvements.
UNLABELLED: Translocator protein (TSPO) is expressed at a low level in healthy brain and is upregulated during inflammatory processes that may occur in neurodegenerative diseases. Thus, TSPO may be a suitable in vivo indicator of neurodegeneration. Here, we quantified the (18)F-DPA-714 radioligand in healthy TSPO-genotyped volunteers and developed a method to eliminate the need for invasive arterial blood sampling. METHODS: Ten controls (7 high-affinity binders [HABs] and 3 mixed-affinity binders [MABs]) underwent (18)F-DPA-714 PET with arterial and venous sampling. (18)F-DPA-714 binding was quantified with a metabolite-corrected arterial plasma input function, using the 1- and 2-tissue-compartment models (TCMs) as well as the Logan analysis to estimate total volume distribution (V(T)) in the regions of interest. Alternative quantification methods were tested, including tissue-to-plasma ratio or population-based input function approaches normalized by late time points of arterial or venous samples. RESULTS: The distribution pattern of (18)F-DPA-714 was consistent with the known distribution of TSPO in humans, with the thalamus displaying the highest binding and the cerebellum the lowest. The 2-TCM best described the regional kinetics of (18)F-DPA-714 in the brain, with good identifiability (percentage coefficient of variation < 5%). For each region of interest, V(T) was 47.6% ± 6.3% higher in HABs than in MABs, and estimates from the 2-TCM and the Logan analyses were highly correlated. Equilibrium was reached at 60 min after injection. V(T) calculated with alternative methods using arterial samples was strongly and significantly correlated with that calculated by the 2-TCM. Replacement of arterial with venous sampling in these methods led to a significant but lower correlation. CONCLUSION: Genotyping of subjects is a prerequisite for a reliable quantification of (18)F-DPA-714 PET images. The 2-TCM and the Logan analyses are accurate methods to estimate (18)F-DPA-714 V(T) in the human brain of both HAB and MAB individuals. Population-based input function and tissue-to-plasma ratio with a single arterial sample are promising alternatives to classic arterial plasma input function. Substitution with venous samples is promising but still requires methodologic improvements.
Authors: Stefanie M A Willekens; Donatienne Van Weehaeghe; Philip Van Damme; Koen Van Laere Journal: Eur J Nucl Med Mol Imaging Date: 2016-12-08 Impact factor: 9.236
Authors: Bastian Zinnhardt; Michael Müther; Wolfgang Roll; Philipp Backhaus; Astrid Jeibmann; Claudia Foray; Cristina Barca; Christian Döring; Bertrand Tavitian; Frédéric Dollé; Matthias Weckesser; Alexandra Winkeler; Sven Hermann; Stefan Wagner; Heinz Wiendl; Walter Stummer; Andreas H Jacobs; Michael Schäfers; Oliver M Grauer Journal: Neuro Oncol Date: 2020-07-07 Impact factor: 12.300