Feasibility of Longitudinal Brain PET with Real-Time Arterial Input Function in Rats
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RESEARCH ARTICLE
Feasibility of Longitudinal Brain PET with Real-Time Arterial Input Function in Rats David Rey-Bretal,1 Alexis Moscoso,2 Noemí Gómez-Lado,1 Anxo Fernández-Ferreiro,3 Jesús Silva-Rodríguez,2 Álvaro Ruibal,1,2 Pablo Aguiar 1,2 1
Molecular Imaging Group, Department of Radiology, Faculty of Medicine, University of Santiago de Compostela (USC), IDIS, Campus Vida, 15782, Santiago de Compostela, Spain 2 Nuclear Medicine Department and Molecular Imaging Group, IDIS and University Hospital Santiago de Compostela (CHUS), Travesía da Choupana s/n, 15706, Santiago de Compostela, Spain 3 Pharmacy Department and Pharmacology Group, IDIS and University Hospital CHUS, Travesía da Choupana s/n, 15706, Santiago de Compostela, Spain
Abstract Purpose: Preclinical dynamic brain PET studies remain hampered by the limitations related to the measurement of the arterial input function (AIF). In this regard, the use of an arterial-venous shunt is a promising method for the generation of real-time AIFs, but its application in longitudinal studies is still impeded by the cumbersome surgeries and high failure rates. We studied the feasibility and reproducibility of double arterial-venous shunt strategies for conducting longitudinal PET studies with real-time AIFs in rats. Procedures: We studied the feasibility of double arterial-venous shunts in rats in the right/left inguinal region and evaluated inter-animal and intra-animal AIF reproducibilities. Image-derived input function (IDIF) was also obtained for comparison. Dynamic brain FDG PET studies were conducted to estimate kinetic constants and Cerebral Metabolic Rate of Glucose (CMRglc) obtained from standard 2-tissue compartment (2TCM) and Patlak analysis. Results: We showed that longitudinal AIFs from double arterial-venous shunts can be obtained with very high success rate of the surgeries (88 %). Our results provided highly reproducible AIF measurements with low inter-animal variabilities (11 %) and intra-animal variabilities (5–10 %) that were included into the kinetic models, such that longitudinal rate constants and CMRglc can be efficiently estimated without bias associated to the double shunt. Our results indicated that longitudinal IDIF can be also generated without bias along time but showing higher intra-animal uncertainties. Conclusions: We have demonstrated the feasibility and high reproducibility of conducting longitudinal AIF measurements and consequently accurate kinetic modeling using arterial shunt method. Key words: Arterial input function, Cerebral metabolic glucose rate, Dynamic PET, Kinetic modeling, Preclinical PET
Electronic supplementary material The online version of this article (https:// doi.org/10.1007/s11307-020-01556-y) contains supplementary material, which is available to authorized users. Correspondence to: Pablo Aguiar; e-mail: pablo.aguiar.fernandez@sergas. es
Introduction Dynamic PET studies represent the reference technique for in vivo evaluation of the exchanges of drugs or radiotracers across the blood-brain barrier (BBB), recept
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