title: Anticancer activity using positron emission tomography-computed tomography and pharmacokinetics of β-eudesmol in human cholangiocarcinoma xenografted nude mouse model.
abstract: Cholangiocarcinoma (CCA) is an important public health problem in several parts of South East Asia, particularly in Thailand. The limited availability of effective diagnostic tools for early stage CCA, including chemotherapeutic options, constitutes a major problem for treatment and control of CCA. The aim of the present study was to assess the anti-CCA activity and pharmacokinetics of β-eudesmol in CCA-xenografted nude mouse model and healthy mice. Positron emission tomography-computed tomography (PET-CT) with (18)F-fluorodeoxyglucose was used for detecting and monitoring tumour development, and PET-CT with technetium-99m was used to investigate its pharmacokinetics property. Results support the role of PET-CT as a potential tool for detecting and monitoring the progress of lung metastasis. Tumour size and lung metastasis were significantly inhibited by 91.6% (of baseline) and 95% (of total lung mass), respectively, following treatment with high-dose β-eudesmol (100 mg/kg body weight for 30 days). Survival time was prolonged by 64.4% compared with untreated controls. Systemic clearance of the compound was rapid, particularly during the first 60 min. The compound was distributed to the vital organs at maximum levels 2 h after oral administration and 15 min after intravenous injection. Results from the present study suggest the potential of β-eudesmol as a promising candidate for further development as an anti-CCA drug with respect to its pharmacodynamics and pharmacokinetic properties. PET-CT, with radiotracers (18)F-fluorodeoxyglucose and technetium-99m, was shown to be a reliable tool in the investigation of anti-CCA and pharmacokinetic properties of β-eudesmol in CCA-xenografted and healthy mice.
authors.affiliation: Chulabhorn International College of Medicine, Thammasat University, Pathum Thani, Thailand; Center of Excellence in Pharmacology and Molecular Biology of Malaria and Cholangiocarcinoma, Thammasat University, Pathum Thani, Thailand.
authors.forename: Tullayakorn
authors.initials: T
authors.lastname: Plengsuriyakarn
authors.forename: Juntra
authors.initials: J
authors.lastname: Karbwang
authors.forename: Kesara
authors.initials: K
authors.lastname: Na-Bangchang
mesh_terms: D065966:Absorption, Physicochemical; D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use / Q000633:toxicity; D001650:Bile Duct Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology; D001653:Bile Ducts, Intrahepatic; D045744:Cell Line, Tumor; D018281:Cholangiocarcinoma / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D049268:Positron-Emission Tomography; D045787:Sesquiterpenes, Eudesmane / Q000493:pharmacokinetics* / Q000494:pharmacology* / Q000627:therapeutic use / Q000633:toxicity; D014018:Tissue Distribution; D014057:Tomography, X-Ray Computed; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D045787:Sesquiterpenes, Eudesmane; C051082:beta-eudesmol
keywords: anti-CCA; cholangiocarcinoma; pharmacokinetics; positron emission tomography-computed tomography; β-eudesmol