Kumar Divesh, Kumar Vijay, Little David G, Howman-Giles Robert B, Wong Effie, Ali Sinan O
Department of Nuclear Medicine, University of Macquarie, Department of Biological Science, The Children's Hospital at Westmead and the Westmead Hospital, Westmead, Australia.
J Orthop Sci. 2006 Oct;11(5):512-20. doi: 10.1007/s00776-006-1046-5.
There is an emerging interest in utilizing local and systemic administration of bisphosphonates in orthopedics. The primary objective of this study was to use (99m)Tc-pamidronate ((99m)Tc-PAM) as a tool and compare bone and tissue uptake by local versus systemic administration.
(99m)Tc-PAM was administered intravenously (i.v.), subcutaneously (s.c.) and by direct application (d.a.) on a surgically exposed and fractured femur (d.a.#f). The animals were imaged at 2 h and 24 h after administration and then killed. Organs were harvested, and their radioactivity was estimated. Specific uptake in the right femur was compared between groups, as was systemic exposure to (99m)Tc PAM.
Bone uptake of (99m)Tc-PAM in the i.v. and s.c. groups was 2.2 +/- 0.15 and 0.65 +/- 0.07% ID/g, respectively, at the 2 h time point. Uptake by surgically exposed right femur (d.a) was 5.15 +/- 0.26% ID/g, 134% higher than the femoral uptake by the i.v. method (P < 0.05). In the presence of exposed bone when the femur was fractured (d.a.#f), the uptake was 7.89 +/- 0.46% ID/g, a further 50% increase (P < 0.05). The uptake of (99m)Tc-PAM increased after 24 h of application to 2.4 +/- 0.15, 1.53 +/- 0.09, 7.94 +/- 0.99, and 13.2 +/- 0.80% ID/g) for i.v., s.c., d.a., and d.a.#f methods, respectively. The increases in uptake for the d.a. methods were significantly higher than for the local methods at the 24-h time point (P < 0.05). Although renal uptake was comparable with the i.v. and s.c. methods (0.22 +/- 0.03 and 0.22 +/- 0.04% ID/g), it was significantly lower with the d.a. methods (0.05 +/- 0.07 and 0.16 +/- 0.07% ID/g) (P < 0.05). The corresponding urinary excretion was 55%, 45%, 36%, and 35% of the injected dose at 24 h.
The results indicate that the bone uptake of (99m)Tc-PAM was significantly higher (P = 0.001) and the kidney uptake significantly lower (P = 0.004) with the d.a. methods than with the i.v. or s.c. method. The findings indicate the need for further study into the potential of local administration of bisphosphonates in the presence of orthopedic indications.
在骨科领域，利用双膦酸盐进行局部和全身给药正受到越来越多的关注。本研究的主要目的是使用锝-99m帕米膦酸盐（锝-99m-PAM）作为工具，比较局部给药与全身给药时骨骼和组织的摄取情况。
将锝-99m-PAM通过静脉注射（i.v.）、皮下注射（s.c.）以及直接应用于手术暴露且骨折的股骨（直接应用#骨折，d.a.#f）。给药后2小时和24小时对动物进行成像，然后处死动物。收集器官并估计其放射性。比较各组右股骨的特异性摄取情况以及锝-99m-PAM的全身暴露情况。
在2小时时间点，静脉注射组和皮下注射组中锝-99m-PAM的骨骼摄取分别为2.2±0.15%ID/g和0.65±0.07%ID/g。手术暴露的右股骨（直接应用）摄取为5.15±0.26%ID/g，比静脉注射法的股骨摄取高134%（P<0.05）。当股骨骨折且有暴露骨时（直接应用#骨折），摄取为7.89±0.46%ID/g，进一步增加了50%（P<0.05）。应用24小时后，静脉注射、皮下注射、直接应用和直接应用#骨折法的锝-99m-PAM摄取分别增加到2.4±0.15%ID/g、1.53±0.09%ID/g、7.94±0.99%ID/g和13.2±0.80%ID/g。在24小时时间点，直接应用法的摄取增加显著高于局部法（P<0.05）。尽管肾脏摄取与静脉注射和皮下注射法相当（分别为0.22±0.03%ID/g和0.22±0.04%ID/g），但直接应用法的肾脏摄取显著更低（分别为0.05±0.07%ID/g和0.16±0.07%ID/g）（P<0.05）。24小时时相应的尿排泄量分别为注射剂量的55%、45%、36%和35%。
结果表明，与静脉注射或皮下注射法相比，直接应用法的锝-99m-PAM骨骼摄取显著更高（P = 0.001），肾脏摄取显著更低（P = 0.004）。这些发现表明需要进一步研究在骨科适应症存在时双膦酸盐局部给药的潜力。
