Radiosynthesis and pharmacokinetics of [¹⁸F]fluoroethyl bufalin in hepatocellular carcinoma-bearing mice

Figures & data

Scheme 1 A scheme of fluoroethyl bufalin and [¹⁸F]fluoroethyl bufalin synthesis.

Abbreviation: DMF, N,N-dimethylformamide.

Figure 1 HPLC chromatogram of [¹⁹F]fluoroethyl bufalin and [¹⁸F]fluoroethyl bufalin.

Notes: HPLC chromatogram of (isocratic, 0.05 mol/L phosphate buffer [pH =7.0], flow 1 mL/min) (A) [¹⁹F]fluoroethyl bufalin, T_R =17.78 min (UV =280 nm) and (B) [¹⁸F]fluoroethyl bufalin, T_R =17.86 min.
Abbreviations: DAD, diode array detector; HPLC, high-performance liquid chromatography; RCP, radiochemical purity; T_R, retention time; UV, ultraviolet.

Figure 2 Stability of [¹⁸F]fluoroethyl bufalin at different intervals in 0.1 mol/L PBS (A) and mouse serum (B).

Abbreviations: PBS, phosphate-buffered saline; RCP, radiochemical purity.

Figure 3 Biodistributions of [¹⁸F]fluoroethyl bufalin in SMMC-7721 (A) and HepG2 (B) xenograft-bearing nude mice.

Notes: SMMC-7721 (A) and HepG2 (B) mice were injected with 7.4 MBq of [¹⁸F]fluoroethyl bufalin, and biodistribution was studied at 45, 120 and 240 min after injection. Radioactivity accumulation was expressed as %ID/g after a single intravenous injection of 7.4 MBq of [¹⁸F]fluoroethyl bufalin in 0.5 mL at 45, 120, and 240 min (n=5/group, mean ± SD). %ID/g, percentage of injected dose per gram of tissue per body weight.
Abbreviation: T, tumor.

Table 1 Biodistribution of [¹⁸F]fluoroethyl bufalin in nude mice

Tissue	SMMC-7721			HepG2
	45 min	120 min	240 min	45 min	120 min	240 min
Tumor	2.31±0.71	4.63±0.94	4.24±0.86	2.59±0.64	4.69±0.92	4.27±0.50
Blood	2.24±0.71	1.93±0.45	1.82±0.22	2.57±0.49	2.54±0.29	1.85±0.37
Heart	4.06±0.38	4.31±0.30	2.64±0.32	4.06±0.38	4.31±0.30	3.66±0.72
Liver	15.79±0.73	11.46±1.3	7.51±1.17	19.74±0.28	10.46±0.44	6.51±1.17
Spleen	3.49±1.49	2.79±1.00	1.82±0.16	3.95±0.80	2.85±0.19	1.69±0.13
Lung	3.66±0.72	3.10±0.20	2.57±0.38	3.43±1.17	3.04±0.29	2.91±0.22
Kidney	7.17±0.34	4.21±0.29	3.21±0.57	7.88±0.42	4.32±0.43	3.67±0.51
Stomach	3.51±0.93	2.73±0.36	1.46±0.13	3.43±0.79	2.57±0.38	1.51±0.07
Intestine	4.45±0.34	4.50±0.55	4.73±0.88	3.10±0.54	4.92±0.65	5.24±0.19
Femur	3.19±2.07	3.65±0.13	6.55±2.21	2.21±0.5	3.87±0.37	6.61±1.30
Muscle	2.76±0.48	3.63±0.94	3.24±0.86	2.08±0.42	3.01±0.23	2.40±0.54
Brain	4.27±0.50	4.13±0.42	3.96±0.11	3.44±0.44	4.04±0.45	3.54±0.37
Tumor/liver	0.15±0.97	0.40±0.72	0.56±0.74	0.13±2.28	0.45±2.09	0.66±0.43

Notes: Radioactivity accumulation was expressed as %ID/g after a single intravenous injection of 7.4 MBq of [¹⁸F]fluoroethyl bufalin in 0.5 mL at 45, 120, and 240 min (n=5/group, mean ± SD). %ID/g, percentage of injected dose per gram of tissue per body weight.

Figure 4 The blood drug concentration–time curve for [¹⁸F]fluoroethyl bufalin in the ICR mice.

Notes: The blood drug concentration–time curve for [¹⁸F]fluoroethyl bufalin in the ICR mice till 10 hour pi. %ID/g, percentage of injected dose per gram of tissue per body weight.
Abbreviations: ICR, Institute of Cancer Research; pi, post injection.

Table 2 Pharmacokinetic parameters of the [¹⁸F]fluoroethyl bufalin in ICR mice

Parameter (units)	[^18F]fluoroethyl bufalin
K10 (min^−1)	0.048
K12 (min^−1)	0.921
K21 (min^−1)	0.038
Vd (Vd)	0.029
CL (L/min/kg)	0.001
t1/2α (min)	0.693
t1/2β (min)	510.223
AUC(0–t) (μg/L·min)	540.137
AUC(0–∞) (μg/L·min)	851.462

Notes: Pharmacokinetic parameters of [¹⁸F]fluoroethyl bufalin in the ICR mice till 10 h post injection. K₁₀, elimination rate constant; K₁₂, elimination rate constant from central compartment to peripheral compartment; K₂₁, elimination rate constant from peripheral compartment to central compartment; Vd, apparent volume of distribution.

Abbreviations: CL, clearance; AUC, area under concentration time–curve; ICR, Institute of Cancer Research; t_1/2α, half-life of distribution; t_1/2β, half-life of elimination.

Figure 5 Dynamic small-animal PET scans obtained for [¹⁸F]fluoroethyl bufalin with SMMC-7721 T-bearing mice and HepG2 T-bearing mice.

Notes: Coronal whole-body slices that contained Ts are shown; arrows indicate Ts.
Abbreviations: PET, positron emission tomography; Ts, tumors.

Figure 6 Quantified time–activity curves of major organs in SMMC-7721 and HepG2 T-bearing mice.

Notes: (A) Quantified time–activity curves of major organs (T, liver, heart, and kidney) after injection of 7.4 MBq [¹⁸F]fluoroethyl bufalin in SMMC-7721 T-bearing mice (n=3). (B) Quantified time–activity curves of major organs (T, liver, heart, and kidney) after injection of 7.4 MBq [¹⁸F]fluoroethyl bufalin in HepG2 T-bearing mice (n=3). %ID/g, percentage of injected dose per gram of tissue per body weight.
Abbreviation: T, tumor.