Schiper Luis, Faintuch Bluma Linkowski, Badaró Roberto José da Silva, Oliveira Erica Aparecida de, Chavez Victor E Arana, Chinen Elisangela, Faintuch Joel
Universidade Federal da Bahia, Faculdade de Medicina, Departamento de Ortopedia, Bahia/BA, Brazil.
Instituto de Energia e Pesquisa Nuclear, Centro de Radiofarmácia, São Paulo/SP, Brazil.
Clinics (Sao Paulo). 2016 Oct 1;71(10):617-625. doi: 10.6061/clinics/2016(10)11.
: Conventional imaging methods are excellent for the morphological characterization of the consequences of osteonecrosis; however, only specialized techniques have been considered useful for obtaining functional information. To explore the affinity of radiotracers for severely devascularized bone, a new mouse model of isolated femur implanted in a subcutaneous abdominal pocket was devised. To maintain animal mobility and longevity, the femur was harvested from syngeneic donors. Two technetium-99m-labeled tracers targeting angiogenesis and bone matrix were selected.
: Medronic acid and a homodimer peptide conjugated with RGDfK were radiolabeled with technetium-99m, and biodistribution was evaluated in Swiss mice. The grafted and control femurs were evaluated after 15, 30 and 60 days, including computed tomography (CT) and histological analysis.
: Radiolabeling achieved high (>95%) radiochemical purity. The biodistribution confirmed good blood clearance 1 hour after administration. For 99mTc-hydrazinonicotinic acid (HYNIC)-E-[c(RGDfK)2, remarkable renal excretion was observed compared to 99mTc-methylene diphosphonate (MDP), but the latter, as expected, revealed higher bone uptake. The results obtained in the control femur were equal at all time points. In the implanted femur, 99mTc-HYNIC-E-[c(RGDfK)2 uptake was highest after 15 days, consistent with early angiogenesis. Regarding 99mTc-MDP in the implant, similar uptake was documented at all time points, consistent with sustained bone viability; however, the uptake was lower than that detected in the control femur, as confirmed by histology.
: 1) Graft viability was successfully diagnosed using radiotracers in severely ischemic bone at all time points. 2) Analogously, indirect information about angiogenesis could be gathered using 999mTc-HYNIC-E-[c(RGDfK)2. 3) These techniques appear promising and warrant further studies to determine their potential clinical applications.
传统成像方法在骨坏死后果的形态学特征描述方面表现出色；然而，只有专门技术才被认为对获取功能信息有用。为了探究放射性示踪剂对严重缺血骨的亲和力，设计了一种将分离的股骨植入腹部皮下袋的新型小鼠模型。为了维持动物的活动能力和寿命，股骨取自同基因供体。选择了两种靶向血管生成和骨基质的锝-99m标记示踪剂。
用锝-99m对亚甲基二膦酸和与RGDfK偶联的同二聚体肽进行放射性标记，并在瑞士小鼠中评估其生物分布。在15、30和60天后对移植的股骨和对照股骨进行评估，包括计算机断层扫描（CT）和组织学分析。
放射性标记实现了高（>95%）放射化学纯度。生物分布证实给药1小时后血液清除良好。与锝-99m亚甲基二膦酸盐（MDP）相比，对于锝-99m-肼基烟酸（HYNIC）-E-[c（RGDfK）2]，观察到显著的肾脏排泄，但正如预期的那样，后者显示出更高的骨摄取。在所有时间点，对照股骨获得的结果均相同。在植入的股骨中，锝-99m-HYNIC-E-[c（RGDfK）2]摄取在15天后最高，这与早期血管生成一致。关于植入物中的锝-99m-MDP，在所有时间点记录到相似的摄取，这与持续的骨活力一致；然而，如组织学所证实的，其摄取低于对照股骨中检测到的摄取。
1）使用放射性示踪剂在所有时间点成功诊断了严重缺血骨中的移植活力。2）类似地，使用锝-99m-HYNIC-E-[c（RGDfK）2]可以收集有关血管生成的间接信息。3）这些技术似乎很有前景，值得进一步研究以确定其潜在的临床应用。
