ORIGINAL ARTICLE Longitudinal assessment of cerebral 5-HT 2A receptors in healthy elderly volunteers: an [ 18 F]-altanserin PET study Lisbeth Marner & Gitte M.Knudsen & Steven Haugbøl & Søren Holm & William Baaré & Steen G.Hasselbalch Received: 21 June 2008 / Accepted: 23 August 2008 / Published online: 1 October 2008 # Springer-Verlag 2008 Abstract Purpose The serotonin 2A (5-HT 2A ) receptor is of interest in several psychiatric and neurological diseases. In the present study we investigated the longitudinal stability of 5-HT 2A receptors and the stability of the quantification procedure in the elderly in order to be able to study elderly patients with neuropsychiatric diseases on a longitudinal basis. Methods [ 18 F]-Altanserin PET wasused to quantify 5- HT 2A receptors in 12 healthy elderly individuals at baseline and at2 years in six volumes of interest. A bolus/infusion protocol was used to achieve the binding potential, BP P . The reproducibility as assessed in terms of variability and the reliability as assessed in terms of intraclass correlation coefficient (ICC) were used to compare inter- and intra- observer stability and to evaluate the effects of increasing complexity of partialvolume (PV)corrections. We also compared the stability of ourmeasurements over 2 years with the stability of data from an earlier study with 2-week test–retest measurements. Results BP P was unaltered at follow-up without the use of PV correction and when applying two-tissue PV correction, tes retest reproducibility was 12–15% and reliability 0.45–0.67 thelargebilateral regionssuch astheparietal, temporal, occipital and frontal cortices, while orbitofrontal and anterior cingulate cortical regions were less stable. The use ofPV correction decreased the variability but also decreased the between-subject variation, thereby worsening the reliabilit Conclusion In healthy elderly individuals, brain 5-HT 2A receptor binding remains stable over 2 years, and accepta reproducibility and reliability in larger regionsand high intra-and interobserver stability allow the use of [ 18 F]- altanserin in longitudinal studies of patients with neuropsy chiatric disorders. Keywords Brain . Serotonin . Test–retest . Reproducibility . Partial volume correction . 5-HT Introduction Serotonin transmission contributes to the expression of normalbehaviour, personality and cognition across the human life-span. The advent of positron emission tomog- raphy (PET) has enabled the investigation of various aspectsofserotonintransmission. A well-documented decrease in serotonin 2A (5-HT 2A ) receptor binding is seen in Alzheimer’s disease [1, 2],and a decrease of 6–8% per decade is seen during normal ageing [ 3, 4]. Quantification of 5-HT 2A receptors with [ 18 F]-altanserin, a highly selective5-HT 2A receptorantagonist, can be performed with a bolus/infusion protocol where steady- state tracer levels are obtained in blood and brain [ 5]. The Eur J Nucl Med Mol Imaging (2009) 36:287–293 DOI 10.1007/s00259-008-0945-4 L. Marner (*) : G. M. Knudsen : S. Haugbøl : S. G. Hasselbalch Neurobiology Research Unit, N9201, University Hospital Rigshospitalet, Blegdamsvej 9, DK-2100 Copenhagen O, Denmark e-mail: lisbeth.marner@nru.dk S. Holm PET and Cyclotron Unit, Department of Clinical Physiology and Nuclear Medicine, Rigshospitalet, Copenhagen, Denmark W. Baaré Danish Research Center for Magnetic Resonance, Hvidovre Hospital, Copenhagen, Denmark S. G. Hasselbalch Memory Disorders Research Unit, The Neuroscience Center, Copenhagen, Denmark