PT  - JOURNAL ARTICLE
AU  - Tuulia Huhtala
AU  - Jussi Rytkonen
AU  - Pekka Poutiainen
AU  - Patrick Sweeney
TI  - Arterial input function combined with PET to follow longitudinally neuroinflammation in rats
DP  - 2017 May 01
TA  - Journal of Nuclear Medicine
PG  - 1244--1244
VI  - 58
IP  - supplement 1
4099  - http://jnm.snmjournals.org/content/58/supplement_1/1244.short
4100  - http://jnm.snmjournals.org/content/58/supplement_1/1244.full
SO  - J Nucl Med2017 May 01; 58
AB  - 1244Objectives: Dynamic PET imaging using radioligands without suitable reference region in brain requires metabolite corrected arterial input function (AIF) for quantification by compartmental analysis. As an example, activation of translocator protein (TSPO) associated to neuroinflammation is uniform in brain and hence reference tissue modeling cannot apply for dynamic PET quantification. Traditional techniques to generate full AIF using blood sampling are not feasible due to limited blood volume of rodents. Significant blood loss may also bias tracer pharmacokinetics. Furthermore, multiple blood sampling can typically be conducted only as a terminal procedure preventing longitudinal studies within individual. Inflammation is associated with many neurodegenerative diseases, including multiple sclerosis (MS), Parkinson’s disease (PD), Alzheimer’s disease (AD), Huntington’s disease (HD), and traumatic brain injury (TBI).18F-FEPPA is second-generation TSPO ligand which has been used in clinical PET imaging of neuroinflammation e.g. in PD, AD and schizophrenia.Methods: Lipopolysaccharide (LPS) is a known potent immunostimulant, which can be used to induce acute local neuroinflammation. In this study dynamic PET imaging of 18F-FEPPA was performed after unilateral infusion of LPS to rat striatum. Dynamic PET scan was performed from the same individuals on D1, D8 and D15 and blood activity was measured simultaneously from the shunt using coincidence counter. Further, 18F plasma fraction and 18F-FEPPA parent fractions were determined over PET scan.Results: With arteriovenous shunt and coincidence counter blood input function could be obtained from rodents during dynamic PET scan without blood loss. Correction for plasma activity and parent fraction was achieved from minimal blood volume samples collected from the shunt during the scan. This nonsurgical novel approach required only minimal blood sampling allowing longitudinal PET studies with AIF in rats.Conclusion: As a summary, applying this novel methodology to generate AIF simultaneously with pre-clinical PET imaging provides more translational and reliable approach to monitor progression of e.g. inflammation applicable for several neurodegenerative rodent models. Research Support: