Synthesis and evaluation of an [18F] labelled imidazopyridine, for the study of the peripheral benzodiazepine binding sites using PET

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dc.contributor.authorKatsifis, Aen_AU
dc.contributor.authorMattner, Fen_AU
dc.contributor.authorPham, TQen_AU
dc.contributor.authorFookes, CJRen_AU
dc.contributor.authorGreguric, Ien_AU
dc.contributor.authorBerghofer, PJen_AU
dc.contributor.authorBallantyne, Pen_AU
dc.contributor.authorShepherd, Ren_AU
dc.contributor.authorLiu, Xen_AU
dc.date.accessioned2020-09-17T06:16:53Zen_AU
dc.date.available2020-09-17T06:16:53Zen_AU
dc.date.issued2007-05-01en_AU
dc.date.statistics2020-09-17en_AU
dc.descriptionThis abstract was presented at the XVIIth International Symposium on Radiopharmaceutical Sciences, April 30 May 4 2007, Aachen, Germany and was published in the Journal of Nuclear Medicine, May 1, 2007 vol. 48, Supplement 2.en_AU
dc.description.abstractObjectives: The purpose of this study was to synthesise and evaluate the F-18 imidazopyridine 2-(2-(4-(3-fluoropropoxy)phenyl)-6,8-dichloroimidazo[1,2-a]pyridin-3-yl)-N-methyl-N-phenylacetamide 1 as a potential tracer for the study of PBBS using PET. Methods: [18F]1 has been prepared by nucleophilic substitution of the tosylethyloxy precursor with 18F-fluoride in the presence of K222, K2CO3 in ACN at 100°C for 5 mins followed by RP-HPLC purification. The biodistribution of [18F]1 was performed in SD rats and brain and peripheral tissues were analysised at 15, 30 min, 1, and 4 h p.i. The specificity and selectivity of the tracer was assessed by pre-treatment with the PBBS ligands PK11195 and Ro 5-4864 and with Flumazenil for CBR at 1 mg/kg 5 min prior to injection of [18F]1. Results: In vitro binding of 1 indicated an IC50 of 7.4 nM for PBBS and >4000 nM for the CBR. [18F]1 was synthesised in 40-55 % radiochemical yield non-decay corrected and with > 95 % radiochemical purity. The specific activity ranged from 37-80 GBq/μmol (non optimised). Biodistribution studies indicated uptake of [18F]1 in tissue expressing PBBS. The adrenals showed high uptake, increasing from 9% ID/g at 30 min p.i to 11% at 4 h. In the kidneys the activity peaked at 15 min p.i.(5%) and decreased over time to 3.6% at 4h. In the heart the uptake was maintained at 7% througout the experiment (15 min to 4 h). Bone uptake ranged from 1% (at 15 min) to 2.9% at 4h. [18F]1 readily penetrated the blood-brain barrier with uptake in the olfactory regions ranging from an initial 0.66% at 15 min to 0.26% at 4 h p.i. The concentration in the blood was significantly lower than the brain regions (0.7% at 15 min to 0.15% at 4 h). Pre-treatment with PK 11195, Ro 5-4864 and non radioactive analogue 1 significantly decreased the uptake in the brain and peripheral organs except in the adrenals which showed a modest increase or no change in uptake. Flumazenil had no effect in the uptake of [18F]1 in the brain or peripheral organs. Conclusions: These results demonstrate the specific PBBS uptake of [18F]1 in vivo. Therefore [18F]1 warrants further investigation as a potential PET tracer for the PBBS. Copyright © 2020 Society of Nuclear Medicine and Molecular Imagingen_AU
dc.identifier.citationKatsifis, A., Mattner, F., Pham, T., Fookes, C., Greguric, I., Berghofer, P., Ballantyne, P., Shepherd, R. & Liu, X. (2007). Synthesis and evaluation of an [18F] labelled imidazopyridine, for the study of the peripheral benzodiazepine binding sites using PET. Paper presented to the Society of Nuclear Medicine (SNM) 2007 Annual Meeting, June 02 - 06, 2007, Washington, DC. In Journal of Nuclear Medicine, 48(supplement 2), 300P-300P. Retrieved from http://jnm.snmjournals.org/content/48/supplement_2/300P.3.abstracten_AU
dc.identifier.conferenceenddate6 June 2007en_AU
dc.identifier.conferencenameSociety of Nuclear Medicine (SNM) 2007 Annual Meetingen_AU
dc.identifier.conferenceplaceWashington, DCen_AU
dc.identifier.conferencestartdate2 June 2007en_AU
dc.identifier.issn0161-5505en_AU
dc.identifier.issueS2en_AU
dc.identifier.journaltitleJournal of Nuclear Medicineen_AU
dc.identifier.pagination300Pen_AU
dc.identifier.urihttp://jnm.snmjournals.org/content/48/supplement_2/300P.3.abstracten_AU
dc.identifier.urihttps://apo.ansto.gov.au/dspace/handle/10238/9792en_AU
dc.identifier.volume48en_AU
dc.language.isoenen_AU
dc.publisherSociety of Nuclear Medicine and Molecular Imagingen_AU
dc.subjectSynthesisen_AU
dc.subjectEvaluationen_AU
dc.subjectPositron computed tomographyen_AU
dc.subjectFluoridesen_AU
dc.subjectIn vitroen_AU
dc.subjectRadiochemical analysisen_AU
dc.titleSynthesis and evaluation of an [18F] labelled imidazopyridine, for the study of the peripheral benzodiazepine binding sites using PETen_AU
dc.typeConference Abstracten_AU
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