Anticancer activity using positron emission tomography-computed tomography and pharmacokinetics of β-eudesmol in human cholangiocarcinoma xenografted nude mouse model.

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 18F-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 18F-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. [ABSTRACT FROM AUTHOR]