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

Summary 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.