{"created":"2023-05-15T14:53:30.610355+00:00","id":72869,"links":{},"metadata":{"_buckets":{"deposit":"ebe72ac3-6931-4101-9bf5-f500f8f27b1d"},"_deposit":{"created_by":1,"id":"72869","owners":[1],"pid":{"revision_id":0,"type":"depid","value":"72869"},"status":"published"},"_oai":{"id":"oai:repo.qst.go.jp:00072869","sets":["10:28"]},"author_link":["725131","725135","725144","725141","725130","725138","725132","725137","725143","725139","725133","725129","725140","725142","725145","725128","725136","725134"],"item_10005_date_7":{"attribute_name":"発表年月日","attribute_value_mlt":[{"subitem_date_issued_datetime":"2018-07-10","subitem_date_issued_type":"Issued"}]},"item_10005_description_5":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"Introduction\n[11C]PBB3, a Tau imaging agent, is rapidly metabolized to form a sulfate conjugate ([11C]PBB3-sulfate) in peripheral tissues by sulfotransferase (SULT).1 After the administration of [11C]PBB3 to mice, [11C]PBB3-sulfate was observed also in the brain. The previous report concluded that it was due to the influx of [11C]PBB3-sulfate from blood to brain. However, it is known that SULT is expressed in the brain and [11C]PIB which possesses 6-hydroxybenzothiazole as a fundamental structure (Fig 1) is sulfated in the rat brain.2 It was therefore expected that [11C]PBB3, a [11C]PIB derivative, would be sulfated in the brain. In this study, the sulfate conjugation of [11C]PBB3 in the brain was investigated because the conjugation might affect the kinetic analysis of Tau imaging with [11C]PBB3. In addition, the hydrolysis of [11C]PBB3-sulfate to form parent [11C]PBB3 in the brain was investigated as sulfate conjugates can be hydrolyzed by sulfatase which is expressed in the brain.\n\nMaterials & Methods\nSulfate conjugation of [11C]PBB3 in the brain was evaluated by adding [11C]PBB3 and a sulfate donor, 3'-phosphoadenosine-5'-phosphosulfate (PAPS) to the brain homogenate sample. In mice samples (cerebrum, C57BL/6, 8 wo, n=3), reactions were carried out at 37°C for 30 min. In samples of a rhesus monkey (frontal cortex, Macacca mulatta, male, 23 yo), reactions were carried out at 37°C and the conjugates generated were analyzed at 5, 15, 30 min after starting reaction. In addition to the crude homogenate (around 0.2 g/mL for mice, 0.16 g/mL for monkey), the sulfate conjugation in the supernatant of homogenate was investigated. The conjugation was analyzed using radio-TLC. Similarly, [11C]PBB3-sulfate, which was prepared by O-sulfation of [11C]PBB3 using sulfur trioxide pyridine complex, was incubated in the mice brain homogenate at 37°C for 30 min to evaluate its hydrolysis.\n\nResults\nThe sulfate conjugation of [11C]PBB3 was observed in the mice brain samples with 30 min reaction time, and only 7.7±0.44% and 9.2±0.30% of [11C]PBB3 was conjugated in the crude homogenate and supernatant, respectively (Fig 2A). Meanwhile, [11C]PBB3-sulfate was slowly hydrolyzed to form [11C]PBB3 in the brain sample (3.1±0.13% in the crude homogenate and 3.7±0.20% in the supernatant, Fig 2B).\nThe conjugation rates of [11C]PBB3 in the monkey brain samples were much faster than that in the mice brain samples. The conjugation in the crude homogenate of monkey brain followed first order manner (r2=1.0) up to 91% decrease of [11C]PBB3 and the rate was estimated to be 0.49 min–1(g/mL)–1. The first order kinetics suggested that the hydrolysis rate of [11C]PBB3-sulfate in the monkey brain was much slower than the conjugation rate. Indeed, the conjugation rate and the hydrolysis rate in the supernatant prepared from 0.16 g/mL of monkey brain homogenate were estimated to be 0.35 min-1 and 0.013 min-1, respectively (Fig 3).\n\nDiscussion\nIn mice, [11C]PBB3 slowly but significantly underwent sulfate conjugation in the brain. Therefore, a part of [11C]PBB3-sulfate observed in the mouse brain after [11C]PBB3 administration would be the metabolite generated in the brain. On the other hand, the sulfate conjugation of [11C]PBB3 was quite rapid and apparently irreversible in the monkey brain samples. \nIn this study, large Interspecies differences regarding the sulfate conjugation of [11C]PBB3 in the brain was observed. Therefore, further investigation about the conjugation of [11C]PBB3 in the human brain would be required.\n\nReferences\n1.Hashimoto H, Kawamura K, Takei M et al. [2015] Nucl. Med. Biol. 42: 905–910\n2.Cole GB, Keum G, Liu J et al. [2010] Proc. Natl. Acad. Sci. USA 107: 6222–6227","subitem_description_type":"Abstract"}]},"item_10005_description_6":{"attribute_name":"会議概要（会議名, 開催地, 会期, 主催者等）","attribute_value_mlt":[{"subitem_description":"The XII International Symposium of Functional Neuroreceptor Mapping of the Living Brain","subitem_description_type":"Other"}]},"item_access_right":{"attribute_name":"アクセス権","attribute_value_mlt":[{"subitem_access_right":"metadata only access","subitem_access_right_uri":"http://purl.org/coar/access_right/c_14cb"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"Kikuchi, Tatsuya"}],"nameIdentifiers":[{"nameIdentifier":"725128","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Okada, Maki"}],"nameIdentifiers":[{"nameIdentifier":"725129","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Ishii, Hideki"}],"nameIdentifiers":[{"nameIdentifier":"725130","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Nengaki, Nobuki"}],"nameIdentifiers":[{"nameIdentifier":"725131","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Ono, Maiko"}],"nameIdentifiers":[{"nameIdentifier":"725132","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Okamura, Toshimitsu"}],"nameIdentifiers":[{"nameIdentifier":"725133","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Minamimoto, Takafumi"}],"nameIdentifiers":[{"nameIdentifier":"725134","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Higuchi, Makoto"}],"nameIdentifiers":[{"nameIdentifier":"725135","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Zhang, Ming-Rong"}],"nameIdentifiers":[{"nameIdentifier":"725136","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"菊池 達矢","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"725137","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"岡田 真希","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"725138","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"石井 英樹","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"725139","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"念垣 信樹","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"725140","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"小野 麻衣子","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"725141","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"岡村 敏充","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"725142","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"南本 敬史","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"725143","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"樋口 真人","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"725144","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"張 明栄","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"725145","nameIdentifierScheme":"WEKO"}]}]},"item_language":{"attribute_name":"言語","attribute_value_mlt":[{"subitem_language":"eng"}]},"item_resource_type":{"attribute_name":"資源タイプ","attribute_value_mlt":[{"resourcetype":"conference object","resourceuri":"http://purl.org/coar/resource_type/c_c94f"}]},"item_title":"Sulfate conjugation of [11C]PBB3, a Tau imaging agent, in the brain","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"Sulfate conjugation of [11C]PBB3, a Tau imaging agent, in the brain"}]},"item_type_id":"10005","owner":"1","path":["28"],"pubdate":{"attribute_name":"公開日","attribute_value":"2019-02-21"},"publish_date":"2019-02-21","publish_status":"0","recid":"72869","relation_version_is_last":true,"title":["Sulfate conjugation of [11C]PBB3, a Tau imaging agent, in the brain"],"weko_creator_id":"1","weko_shared_id":-1},"updated":"2023-05-16T08:29:40.517163+00:00"}