title: Synthesis and in vitro cellular uptake of 11C-labeled 5-aminolevulinic acid derivative to estimate the induced cellular accumulation of protoporphyrin IX.
abstract: Protoporphyrin IX (PpIX) accumulation induced by exogenous 5-aminolevulinic acid (ALA) in tumors affects the therapeutic efficacy of ALA-based photodynamic and sonodynamic therapies. To develop a new imaging probe to estimate the ALA-induced PpIX accumulation, (11)C-labeled ALA analog (4), an ALA-dehydratase inhibitor, was radiosynthesized via (11)C-methylation of a Schiff-base-activated precursor in the presence of tetrabutylammonium fluoride, followed by the hydrolysis of ester and imine groups. The cellular uptake of 4 linearly increased with time and was inhibited by ALA and other transporter competitors. Monitoring analog 4 with positron emission tomography might be useful to estimate the ALA-induced PpIX accumulation in tumors.
authors.affiliation: Diagnostic Imaging Group, Molecular Imaging Center, National Institute of Radiological Sciences, 4-9-1 Anagawa, Chiba 263-8555, Japan.
authors.forename: Chie
authors.initials: C
authors.lastname: Suzuki
authors.forename: Koichi
authors.initials: K
authors.lastname: Kato
authors.forename: Atsushi B
authors.initials: AB
authors.lastname: Tsuji
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Kikuchi
authors.forename: Ming-Rong
authors.initials: MR
authors.lastname: Zhang
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Arano
authors.forename: Tsuneo
authors.initials: T
authors.lastname: Saga
mesh_terms: D000622:Aminolevulinic Acid / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics*; D001667:Binding, Competitive; D002250:Carbon Radioisotopes / Q000378:metabolism; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D015394:Molecular Structure; D009369:Neoplasms / Q000737:chemistry*; D017319:Photosensitizing Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics; D049268:Positron-Emission Tomography; D011524:Protoporphyrins / Q000032:analysis / Q000378:metabolism*; D013997:Time Factors
chemical_list: D002250:Carbon Radioisotopes; D017319:Photosensitizing Agents; D011524:Protoporphyrins; D000622:Aminolevulinic Acid; C028025:protoporphyrin IX
keywords: 5-Aminolevulinic acid (ALA); Photodynamic therapy (PDT); Positron emission tomography (PET); Radiosynthesis; Sonodynamic therapy (SDT)