Development of a Novel 99mTc-Chelate–Conjugated Bisphosphonate with High Affinity for Bone as a Bone Scintigraphic Agent

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FIGURE 1.
Chemical structures of ^99mTc-MAG3-HBP (A) and ^99mTc-HYNIC-HBP (B).
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FIGURE 2.
Binding of hydroxyapatite to ^99mTc-MAG3-HBP, ^99mTc-HYNIC-HBP, and ^99mTc-HMDP. Data are expressed as mean ± SD for 3 or 4 experiments. Asterisks indicate statistically significant differences compared with ^99mTc-HMDP with the Dunnett test (P < 0.05).
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FIGURE 3.
RP-HPLC chromatograms of nonradioactive Re-MAG3-HBP (A) and ^99mTc-MAG3-HBP (B). Conditions: flow rate of 1 mL/min with 10% ethanol in 200 mmol/L phosphate buffer (pH 6.0) containing 10 mmol/L tetrabutylammoniumhydroxide.
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FIGURE 4.
RP-HPLC chromatograms of ^99mTc-HYNIC-HBP prepared by coupling of [^99mTc](HYNIC-TFP)(tricine)(3-acetylpyridine) with bisphosphonate derivative (A) and labeling of HYNIC-HBP with ^99mTcO₄⁻, tricine, and 3-acetylpyridine (B). Conditions: flow rate of 1 mL/min with 10% ethanol in 200 mmol/L phosphate buffer (pH 6.0) containing 10 mmol/L tetrabutylammoniumhydroxide.

TABLE 1

Biodistribution of Radioactivity After Intravenous Administration of ^99mTc-MAG3-HBP in Rats

	Time after administration (min)
Tissue	5	10	30	60
Blood	0.98 ± 0.09^*	0.77 ± 0.06	0.29 ± 0.01	0.07 ± 0.01^*
Liver	0.32 ± 0.00	0.29 ± 0.03	0.18 ± 0.01	0.11 ± 0.02
Kidney	2.15 ± 0.33	1.87 ± 0.40	0.85 ± 0.05^*	0.50 ± 0.08^*
Intestine	0.16 ± 0.03^*	0.15 ± 0.03^*	0.13 ± 0.01^*	0.17 ± 0.03^*
Femur	1.80 ± 0.24	2.31 ± 0.22	3.73 ± 0.18^*	4.23 ± 0.25^*
F/B ratio^†	1.86 ± 0.38^*	3.02 ± 0.21^*	13.1 ± 0.85^*	59.7 ± 10.41

↵* Significant differences (P < 0.05) from ^99mTc-HMDP were identified with the Dunnett test.
↵† Femur-to-blood ratio.
Each value is mean ± SD for 4 animals.

TABLE 2

Biodistribution of Radioactivity After Intravenous Administration of ^99mTc-HYNIC-HBP in Rats

	Time after administration (min)
Tissue	5	10	30	60
Blood	0.56 ± 0.05	0.39 ± 0.04^*	0.10 ± 0.01	0.03 ± 0.01
Liver	0.18 ± 0.02	0.12 ± 0.01^*	0.07 ± 0.01^*	0.05 ± 0.01
Kidney	3.19 ± 1.02	1.43 ± 0.09	0.45 ± 0.05	0.26 ± 0.10
Intestine	0.15 ± 0.01^*	0.10 ± 0.01	0.10 ± 0.07	0.05 ± 0.02
Femur	1.90 ± 0.21^*	2.59 ± 0.22^*	3.71 ± 0.30^*	3.96 ± 0.36^*
F/B ratio^†	3.40 ± 0.50^*	6.69 ± 0.43	37.1 ± 4.01^*	123.20 ± 18.30^*

↵* Significant differences (P < 0.05) from ^99mTc-HMDP were identified with the Dunnett test.
↵† Femur-to-blood ratio.
Each value is mean ± SD for 6 animals.

TABLE 3

Biodistribution of Radioactivity After Intravenous Administration of ^99mTc-HMDP in Rats

	Time after administration (min)
Tissue	5	10	30	60
Blood	0.61 ± 0.03	0.32 ± 0.04	0.10 ± 0.01	0.04 ± 0.01
Liver	0.15 ± 0.02	0.08 ± 0.01	0.03 ± 0.00	0.04 ± 0.05
Kidney	3.11 ± 0.23	1.59 ± 0.42	0.46 ± 0.08	0.24 ± 0.03
Intestine	0.12 ± 0.00	0.09± 0.02	0.04 ± 0.01	0.03 ± 0.01
Femur	1.52 ± 0.14	1.97 ± 0.18	2.73 ± 0.15	3.16 ± 0.51
F/B ratio^*	2.49 ± 0.15	6.27 ± 0.94	29.16 ± 4.86	93.40 ± 19.81