Hepatobiliary Secretion Kinetics of Conjugated Bile Acids Measured in Pigs by 11C-Cholylsarcosine PET

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FIGURE 1.
Kinetic model fitted to PET data. Liver VOI comprises 3 separate compartments: blood, hepatocytes, and intrahepatic bile volume. Exchange of ¹¹C-CSar among compartments is described by unidirectional removal of ¹¹C-CSar from blood to hepatocytes by clearance K_mem (mL blood/min/mL liver tissue), backflux of tracer from hepatocytes to blood by rate constant k_backflux (min⁻¹), secretion from hepatocytes into bile canaliculi via BSEP by rate constant k_BSEP (min⁻¹), and ¹¹C-CSar in bile flowing out of liver volume of interest by rate constant k_bile (min⁻¹).
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FIGURE 2.
(A and B) Time courses of ¹¹C-CSar concentrations in flow-weighted mixed-inlet blood (C_in; red), hepatic venous blood (C_out; blue), and liver tissue (C_liver; black) in experiment without catheter in CHD (A) and experiment with catheter in CHD (B). (C) Time course of ¹¹C-CSar concentration in bile samples (C_bile; green) in same experiment as in B.
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FIGURE 3.
Relationship between steady-state hepatic rate of removal of ¹¹C-CSar, v_ss (Eq. 7), calculated from blood measurements, and secretion measured directly from bile sampling, v_bile (Eq. 10), in experiments with catheter in CHD. Line of identity is shown. Identical symbols represent repeated measurements in same pig.

TABLE 1

Hepatobiliary Secretion Kinetics Calculated for ¹¹C-CSar from PET Measurements

	k_backflux min⁻¹		k_BSEP min⁻¹		k_bile min⁻¹		K_int (mL blood/min/mL liver tissue)		K_sys (mL blood/min/mL liver tissue)
Pigs	Weighted mean	95% CI	Weighted mean	95% CI	Weighted mean	95% CI	Weighted mean	95% CI	Weighted mean	95% CI
Without CHD catheter	0.001	0.0008 to 0.0012	0.18	0.15 to 0.21	0.21	0.17 to 0.24	3.32	3.01 to 3.63	0.81	0.74 to 0.88
With CHD catheter	0.028^*	0.005 to 0.050	0.04^*	−0.01 to 0.08	0.09	0.04 to 0.14	0.65^*	−0.27 to 1.57	0.49	0.095 to 0.893

TABLE 2

Hepatobiliary Secretion Kinetics Calculated for ¹¹C-CSar from Blood Measurements

	Q (mL blood/min/mL liver tissue)		E₀		PS_mem (mL blood/min/mL liver tissue)		E_ss		Cl_int (mL blood/min/mL liver tissue)		Cl_sys (mL blood/min/mL liver tissue)
Pigs	Weighted mean	95% CI	Weighted mean	95% CI	Weighted mean	95% CI	Weighted mean	95% CI	Weighted mean	95% CI	Weighted mean	95% CI
Without CHD catheter	0.82	0.76 to 0.88	0.99	0.988 to 0.992	3.63	3.15 to 4.12	0.97	0.94 to 0.99	2.79	1.95 to 3.63	0.79	0.71 to 0.86
With CHD catheter	1.01^*	0.90 to 1.11	0.96^†	0.958 to 0.963	3.53	2.98 to 4.09	0.79^†	0.59 to 0.99	1.70^‡	0.73 to 2.66	0.81	0.60 to 1.02