Biodistribution of newly synthesized PHEA-based polymer-coated SPION in Sprague Dawley rats as magnetic resonance contrast agent

Figures & data

Figure 1 Scheme of ULS and radiolabeled-SPION suspension synthesis [(A) CLS; (B) FLS].

Abbreviations: h, hours; temp, temperature; SPION, superparamagnetic iron oxide nanoparticles; ULS, unradiolabeled SPION; CLS, [¹⁴C]-labeled SPION; FLS, [⁵⁹Fe]-labeled SPION; PSI, poly(succinimide); DMF, N,N-dimethylformamide; DW, deionized water.

Figure 2 Transmission electron microscopy image of polymer-coated iron oxide nanoparticles.

Figure 3 Uptake of the [¹⁴C] from the [¹⁴C]-labeled SPION by organs at various time points in Sprague Dawley rats (A) male (B) female (n=5 for each sex, mean ± standard deviation).

Abbreviations: n, number; h, hours; min, minutes; S Int, small intestine; L Int, large intestine; SPION, superparamagnetic iron oxide nanoparticles.

Figure 4 Uptake of the [⁵⁹Fe] from the [⁵⁹Fe]-labeled SPION by organs at various time points in Sprague Dawley rats (A) male (B) female (n=5 for each sex, mean ± standard deviation).

Abbreviations: n, number; h, hours; min, minutes; S Int, small intestine; L Int, large intestine; SPION, superparamagnetic iron oxide nanoparticles.

Table 1 Average accumulated radioactive material percentage–time profile of 3 main organs of male and female Sprague Dawley rats (n=5 for each sex, mean ± standard deviation)

	Liver (%)		Spleen (%)		Kidney (%)
	Male	Female	Male	Female	Male	Female
[^14C]-SPION
0.5 h	9.31 ± 0.84	5.79 ± 4.36	0.44 ± 0.03	0.36 ± 0.30	2.54 ± 0.10	2.06 ± 0.69
1 h	11.43 ± 0.74	11.43 ± 3.20	0.32 ± 0.13	0.32 ± 0.17	2.25 ± 0.52	2.25 ± 0.60
4 h	13.18 ± 2.20	13.18 ± 0.33	0.67 ± 0.14	0.67 ± 0.20	3.00 ± 0.38	3.00 ± 0.38
12 h	16.32 ± 1.57	15.29 ± 0.12	0.73 ± 0.06	0.71 ± 0.18	3.70 ± 0.63	2.66 ± 0.60
1 day	11.83 ± 2.74	15.89 ± 0.17	0.46 ± 0.15	0.80 ± 0.19	2.33 ± 1.14	3.23 ± 0.55
5 days	11.13 ± 1.03	11.42 ± 0.99	0.40 ± 0.05	0.55 ± 0.10	2.06 ± 0.20	2.48 ± 0.40
10 days	4.51 ± 1.12	4.58 ± 0.38	0.22 ± 0.08	0.30 ± 0.06	0.90 ± 0.21	1.03 ± 0.15
[^59Fe]-SPION
0.5 h	65.83 ± 2.26	67.78 ± 2.25	2.24 ± 0.34	2.67 ± 0.27	0.90 ± 0.17	0.80 ± 0.18
1 h	72.53 ± 2.33	73.47 ± 2.37	2.44 ± 0.49	3.20 ± 0.55	0.58 ± 0.11	0.57 ± 0.24
4 h	82.10 ± 3.29	81.89 ± 4.01	3.01 ± 0.22	3.07 ± 0.67	0.43 ± 0.04	0.28 ± 0.02
12 h	75.82 ± 3.42	80.57 ± 2.53	2.69 ± 0.44	3.50 ± 0.42	0.39 ± 0.03	0.50 ± 0.34
1 day	80.04 ± 1.40	85.68 ± 2.75	2.58 ± 0.34	3.70 ± 0.66	0.43 ± 0.04	0.34 ± 0.05
5 days	61.31 ± 3.23	69.16 ± 1.53	1.24 ± 0.17	2.83 ± 0.58	0.64 ± 0.14	0.82 ± 0.28
10 days	52.23 ± 4.42	66.83 ± 2.54	1.33 ± 0.17	2.45 ± 0.44	0.85 ± 0.13	1.10 ± 0.14
20 days	46.09 ± 2.73	48.75 ± 1.98	0.87 ± 0.10	1.88 ± 0.39	1.29 ± 0.19	1.33 ± 0.15
30 days	40.73 ± 6.00	42.69 ± 3.66	1.29 ± 0.55	1.73 ± 0.35	1.21 ± 0.35	1.09 ± 0.24
50 days	11.93 ± 4.80	17.87 ± 2.61	1.47 ± 0.34	1.76 ± 0.41	0.86 ± 0.17	0.99 ± 0.19

Abbreviations: h, hours; n, number; SPION, superparamagnetic iron oxide nanoparticles.

Table 2 Pharmacokinetic parameter obtained by intravenous injection of [¹⁴C]-SPION and [⁵⁹Fe]-SPION in the liver of Sprague Dawley rats (n=5 for each sex, mean ± standard deviation)

Liver	[^14C]-SPION		[^59Fe]-SPION
	Male	Female	Male	Female
Tmax (h)	12	24	4	4
Cmax (%)	16.32 ± 1.57	17.82 ± 2.04	80.04 ± 1.40	85.70 ± 2.71
t1/2 (day)	6.31 ± 2.04	5.02 ± 2.06	21.62 ± 4.46	23.40 ± 3.71

Abbreviations: h, hours; SPION, superparamagnetic iron oxide nanoparticles; n, number.

Figure 5 Mean blood concentration-time profiles for the [¹⁴C] from the [¹⁴C]-labeled SPION in male and female Sprague Dawley rats after administration of intravenous injection (n=5 for each sex, mean ± standard deviation).

Abbreviations: n, number; h, hours; SPION, superparamagnetic iron oxide nanoparticles.

Figure 6 Mean blood concentration-time profiles for the [⁵⁹Fe] from the [⁵⁹Fe]-labeled SPION in male and female Sprague Dawley rats after administration of intravenous injection (n=5 for each sex, mean ± standard deviation).

Abbreviations: n, number; h, hours; SPION, superparamagnetic iron oxide nanoparticles.

Table 3 The half-life of blood radioactive concentration of [¹⁴C]-SPION and [⁵⁹Fe]-SPION after intravenous injection in male and female Sprague Dawley rats (n=5, mean ± standard deviation)

	[^14C]-SPION		[^59Fe]-SPION
	Male	Female	Male	Female
t1/2 (min)	24.53 ± 7.42	26.47 ± 8.11	15.81 ± 3.11	14.57 ± 2.64

Abbreviations: min, minutes; SPION, superparamagnetic iron oxide nanoparticles; n, number.

Table 4 Cumulative excreted amount by percentage of [¹⁴C] and [⁵⁹Fe] (n=5 for each sex, mean ± standard deviation)

	Male			Female
	Feces	Urine	Total	Feces	Urine	Total
[^14C] excretion (%, 10 days)	23.2 ± 0.88	36.82 ± 2.56	59.84 ± 2.73	23.73 ± 0.84	36.77 ± 2.97	60.51 ± 3.07
[^59Fe] excretion (%, 50 days)	11.96 ± 0.21	2.94 ± 0.05	14.81 ± 0.56	10.45 ± 0.19	2.94 ± 0.05	13.30 ± 0.87

Abbreviation: n, number.

Figure 7 Excretion percentage of the [¹⁴C] from the [¹⁴C]-labeled SPION at various time points in Sprague Dawley rats (n: male=5, female=5, mean ± standard deviation).

Abbreviations: n, number; h, hours; d, day; SPION, superparamagnetic iron oxide nanoparticles.

Figure 8 Excretion percentage of the [⁵⁹Fe] from the [⁵⁹Fe]-labeled SPION at various time points in Sprague Dawley rats (n: male=5, female=5, mean ± standard deviation).

Abbreviations: n, number; h, hours; d, day; SPION, superparamagnetic iron oxide nanoparticles.

Figure 9 T2-weighted magnetic resonance images of rat livers (A) before injection, (B) 10 minutes after injection, (C) 20 minutes after injection, (D) 30 minutes after injection of the cold SPION suspension.

Note: The arrows point to the liver.

Abbreviation: SPION, superparamagnetic iron oxide nanoparticle.