Comparison of [123I]Epidepride & [123I]IBZM SPECT tracers for Brain Dopamine D2 Receptor Imaging using Micro SPECT

Diplôme Master Comparison of [123I]Epidepride & [123I]IBZM SPECT tracers for Brain Dopamine D2 Receptor Imaging using Micro SPECT eng 2013 author Vemula Mani Deep Gupta 763565 director Millet Philippe 0000-0002-5803-0478 668343 Nuclear medicine scanning techniques are non-invasive and with the exclusion of IV injections, are usually reliable, painless diagnostic tools that help physicians diagnose and evaluate various complicated medical conditions. These nuclear medicine imaging tools use radioactive substances called radiotracers, which are injected into the body through IV route to investigate abnormalities in the brain, such as seizures, memory loss, abnormalities in blood flow etc. Relatively, several tracers for the dopamine D2 receptors quantification have been discovered and these have provided considerably new insights to evaluate the role of dopamine in movement disorders, psychiatry and genetic diseases. The importance of this thesis is to quantitatively compare two widely used SPECT radiotracers [123I]IBZM - Iodobenzamide: [123I](S)-2-hydroxy-3-iodo-6-methoxy- (1-ethyl-2-pyrrolidinylmethyl)-benzamide and [123I]Epidepride: [123I](S)-N -((1-ethyl-2-pyrrolidinyl) methyl)-5-iodo-2, 3-dimethoxybenzamide in rodents for the first time, both D2 dopamine antagonists and potential imaging agents used in diagnosing various dopamine receptor dependent neurological and psychiatric disorders. The origin of these substituted benzamides comes from atypical anti psychotic agents. Both [123I]Epidepride and [123I]IBZM are benzamine derivatives with very high affinity for dopamine receptors, which in its labelled form can be used as a SPECT tracer. These SPECT tracers can be used to study alterations in D2/D3 levels in specific brain regions. Significance of alternations of dopamine D2/D3 receptor conditions were widely substantiated in Schizophrenia, Parkinson's, Restless leg syndrome etc. (Kessler RM 1991, Al-Tikriti MS 1994) The purpose of this study was to evaluate the bio distribution and pharmacokinetics of [123I]IBZM and [123I]Epidepride brain SPECT. Even though [123I]IBZM is widely preferred as a D2 receptor-imaging agent, distinctive image standards are stipulated by a relatively low target-to-non target ratio (Olsson H 2001). In Vitro and In vivo animal studies suggest that [123I]Epidepride may be preferred to [123I]IBZM (Kessler RM 1992, Al-Tikriti MS 1994, Scherfler C 2005). This study has shown a systematic comparison of both tracers in rodents by comparing the binding potentials obtained from raw VOI images and pixel wise comparison and proposed new insights about Epidepride kinetics which are currently unaccounted. There was no study conducted on rodents to compare [123I]Epidepride and [123I]IBZM kinetics. [123I]IBZM has been widely used to study the in-vivo characterization of dopamine D2 receptors in humans but rarely studied on mice and rats, after all rodent studies are quite important to conduct fundamental research for studying physiology lying under illnesses like addiction, movement disorders and neurodegenerative diseases etc. Therefore we undertook a direct comparison between these two compounds. Our results comply with previously reported data and show that iodobenzamide – [123I]IBZM has a moderate putamen to cerebellum ratio in rodent brain and less binding potential compared with [123I]Epidepride in striatal regions and extra striatal regions. [123I]Epidepride showed its ability to identify extra striatal regions in the following order, Mid Brain >Temporal Cortex > Frontal > Occipital > Cerebellum and showed its exceptional properties. Thus [123I]Epidepride is superior to [123I]IBZM and shows excellent imaging characteristics of both striatal and extra striatal dopamine D2 receptors (Pinborg 2007). Absolutely [123I]Epidepride is superior to [123I]IBZM but activity from cerebellum cannot be considered as a free and non-specifically bound radio ligand while using reference tissue models with [123I] Epidepride SPECT, therefore finding ways to diminish this will be of appropriate SPECT dopamine IBZM Dewey 616.89 Master en neuroscience 60 Département de psychiatrie 225 false 1221 Neuroimagerie moléculaire en psychiatrie 983 7b918462-adb3-4d24-8448-89e9c7c67d5b Master thesis Private Thesis-Manideep-Version1.pdf 7951214 application/pdf closedAccess Faculté de médecine / Section de médecine clinique / Département de psychiatrie

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Comparison of [¹²³I]Epidepride & [¹²³I]IBZM SPECT tracers for Brain Dopamine D2 Receptor Imaging using Micro SPECT				2013	209	0

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Vemula, Mani Deep Gupta