Fig 1.
Radiosynthesis of 3β-[18F]Fluoro-7α,12α-Diacetoxy-5β-Cholanic Acid Methyl Ester ([18F]FAcCAME) and subsequent deprotection to 3β-[18F]Fluorocholic Acid ([18F]FCA).
i: [18F]Fluoride/K222-K2CO3; DMSO; 120°C; 20 min. ii: 1 M NaOH; 120°C; 10 min.
Fig 2.
FCA concentration-dependent inhibition of [3H]Taurocholate ([3H]TC) and [3H]Estradiol-17β-Glucuronide ([3H]EbG) uptake in NTCP and OATP expressing cell lines respectively.
Values are expressed as mean ± SD (n = 3).
Fig 3.
FCA concentration dependent inhibition of [3H]Taurocholate ([3H]TC) and [3H]Estradiol-17β-Glucuronide ([3H]EbG) in BSEP and MRP2 vesicles respectively.
Values are expressed as mean ± SD (n = 3).
Fig 4.
Maximum intensity projection PET/CT images of [18F]FCA in 2 wild-type FVB-mice at different time points.
Images were generated in AMIDE Medical Image Data Examiner software; slice thickness: 12 mm. In the early phase (3–20 minutes post-injection), the liver, gallbladder and intestines are visible. In a later phase (20–60 minutes post-injection), all radioactivity is excreted from the liver to the gallbladder and intestines. The late phase PET/CT images (6 hours post-injection) show that [18F]FCA remains present only in gallbladder and intestines: visual analysis of all images showed no uptake in other organs than liver, gallbladder and intestines.
Fig 5.
Time-activity curves of [18F]FCA in liver and gallbladder & intestines of wild-type FVB-mice (n = 3).
Uptake of [18F]FCA is expressed as % injected dose and normalized for a 20 g mouse. Values are expressed as mean ± SD.
Table 1.
Metrics of [18F]FCA in liver and gallbladder & intestines in wild-type FVB-mice (n = 3).
Values are expressed as mean ± SD.
Fig 6.
Liver and gallbladder & intestines time-activity curves of [18F]FCA in control, rifampicin and bosentan treated FVB-mice (n = 3 per group).
Uptake of [18F]FCA is expressed as % injected dose and normalized for a 20 g mouse. Values are expressed as mean ± SD.
Fig 7.
Time-activity curves of [18F]FCA in arterial blood for vehicle (green), rifampicin (red) and bosentan (blue) treated mice (n = 3 per group).
Uptake of [18F]FCA is expressed as % injected dose and normalized for a 20 g mouse. Values are expressed as mean ± SD.
Table 2.
Time-activity curve metrics of [18F]FCA in control, rifampicin and bosentan treated animals (n = 3 per group).
Values are expressed as mean ± SD. *: significant difference compared to control group. A p-value of 0.05 was considered significant.