{"created":"2023-05-15T14:52:22.152596+00:00","id":71501,"links":{},"metadata":{"_buckets":{"deposit":"b40cf116-0d8e-4ea2-ae56-a3ee3ef070ed"},"_deposit":{"created_by":1,"id":"71501","owners":[1],"pid":{"revision_id":0,"type":"depid","value":"71501"},"status":"published"},"_oai":{"id":"oai:repo.qst.go.jp:00071501","sets":["10:28"]},"author_link":["703057","703063","703065","703061","703058","703066","703059","703060","703064","703062"],"item_10005_date_7":{"attribute_name":"発表年月日","attribute_value_mlt":[{"subitem_date_issued_datetime":"2014-08-30","subitem_date_issued_type":"Issued"}]},"item_10005_description_5":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"\"Radiosynthesis and preclinical characterization of a 11C-labeled aminolevulinic acid derivative as an imaging probe to estimate tumor protoporphyrin IX accumulation induced by exogenous aminolevulinic acid\"\nObjective: Fluorescence-guided resection, photodynamic therapy, and sonodynamic therapy for tumors using tumor-specific accumulation of protoporphyrin IX (PpIX) induced by 5-aminolevulinic acid (ALA) administration are promising therapeutic strategies. Pretreatment noninvasive imaging to estimate the quantity and spatial distribution of ALA induced PpIX accumulation in tumors is expected to improve the efficacy of ALA-based tumor therapies. PpIX synthesis from exogenous ALA has been reported to be regulated by ALA influx and/or ALA dehydratase (ALAD) activity which catalyzes the first step of the synthesis. In this study, we radiosynthesized a 11C-labeled ALA analog, 5-amino-4-oxo-[6-11C]hexanoic acid ([11C]MALA) and characterized its in vitro and in vivo properties as a positron emission tomography (PET) probe to estimate PpIX accumulation.\nMaterials and methods: [11C]MALA was synthesized via 11C-methylation of a Schiff-base-activated precursor in the presence of tetrabutylammonium fluoride, followed by the hydrolysis of ester and imine groups. In vitro uptake of [11C]MALA and [3H]ALA were determined in five tumor cell lines (AsPC-1, Sk-Br-3, U-87 MG, BxPC-3, and MIA PaCa-2) after 10 min incubation with each tracer at 37°C. The expression levels of ALAD were determined by western blot analysis. Tumor-bearing mice were intravenously injected with the mixture of [11C]MALA and [3H]ALA, and 11C and 3H radioactivity in tissues were measured. Dynamic PET scans were performed for 90 min just after injection of [11C]MALA. In vitro and in vivo accumulation of ALA-induced PpIX was determined by measuring fluorescence in extracts of cells or tumors. \nResults and conclusions: [11C]MALA was obtained in a radiochemical yield (decay uncorrected, referred to [11C]carbon dioxide) of 4.4 ± 1.7% using remote-controlled synthesis module within 35 min from the end of bombardment. In vitro uptake of [11C]MALA in five tumor cell lines was correlated with ALAD expression levels and PpIX accumulation. In vivo biodistribution and dynamic PET studies showed that [11C]MALA was rapidly incorporated into tumors and the tumor-to-muscle ratio of [11C]MALA at 1 min after injection was significantly correlated with that of [3H]ALA. [11C]MALA in tumors was continuously decreased thereafter, and the elimination rate of [11C]MALA from AsPC-1 tumors with the highest ALAD expression level was slower compared with those from other tumors with lower expression levels. These results suggest that the influx and intracellular retention of [11C]MALA reflect ALA influx and ALAD expression levels, respectively. Tumor accumulation of [11C]MALA at 60 min post-injection was strongly correlated with PpIX accumulation in tumor tissues. In conclusion, PET imaging with [11C]MALA has the potential to noninvasively estimate the quantitative and spatial accumulation of exogenous ALA-induced PpIX.","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":"11th Congress of the World Federation of Nuclear Medicine and Biology  る","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":"Suzuki, Chie"}],"nameIdentifiers":[{"nameIdentifier":"703057","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Tsuji, Atsushi"}],"nameIdentifiers":[{"nameIdentifier":"703058","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Kato, Koichi"}],"nameIdentifiers":[{"nameIdentifier":"703059","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Kikuchi, Tatsuya"}],"nameIdentifiers":[{"nameIdentifier":"703060","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Sudou, Hitomi"}],"nameIdentifiers":[{"nameIdentifier":"703061","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"鈴木 千恵","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"703062","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"辻 厚至","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"703063","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"加藤 孝一","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"703064","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"菊池 達矢","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"703065","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"須藤 仁美","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"703066","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":"Radiosynthesis and preclinical characterization of a 11C-labeled aminolevulinicacid","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"Radiosynthesis and preclinical characterization of a 11C-labeled aminolevulinicacid"}]},"item_type_id":"10005","owner":"1","path":["28"],"pubdate":{"attribute_name":"公開日","attribute_value":"2014-09-29"},"publish_date":"2014-09-29","publish_status":"0","recid":"71501","relation_version_is_last":true,"title":["Radiosynthesis and preclinical characterization of a 11C-labeled aminolevulinicacid"],"weko_creator_id":"1","weko_shared_id":-1},"updated":"2023-05-15T19:50:31.429314+00:00"}