Imaging cyclophosphamide-induced intramedullary apoptosis in rats using 99mTc-radiolabeled annexin V.
Imaging cyclophosphamide-induced intramedullary apoptosis in rats using 99mTc-radiolabeled annexin V.
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发表时间：
2001-02
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通讯作者：
F. Blankenberg;Louis Naumovski;Johnathan F. Tait;Anneke M. Post;H. Strauss
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作者：
F. Blankenberg;Louis Naumovski;Johnathan F. Tait;Anneke M. Post;H. Strauss
造血组织的未标记髓内细胞凋亡被认为在骨髓增生异常综合征的病理生理中起重要作用。膜联蛋白V是细胞凋亡早期到中期的特异性标志物，已被应用于骨髓抽吸物的体外研究。一种无创的髓内细胞凋亡在体内的测量方法可以连续监测骨髓增生异常综合征的临床进展，可能是有帮助的。方法采用99mtc放射性标记膜联蛋白V和放射性核素γ相机成像技术，对环磷酰胺诱导的髓内细胞凋亡的部位、程度和严重程度进行了连续研究。结果：静脉注射放射性标记膜联蛋白V优先定位于股骨、骨盆、椎骨和脾脏；在8- 10周龄的动物中，早在注射100 mg/kg环磷酰胺后8小时，这些器官的摄取就明显增加。与低剂量相比，高剂量的环磷酰胺（150 mg/kg）在相同年龄的动物中增加了骨髓和脾组织中的膜联蛋白V摄取，并延迟了这些器官的组织学恢复。年龄较大的动物，5-6月龄，对环磷酰胺治疗的反应较慢，骨髓和脾组织的恢复延迟。结论利用现有的临床放射性核素显像设备，放射标记膜联蛋白V可以无创地检测和直接定量髓内和脾细胞凋亡的程度。膜联蛋白V显像可能在临床诊断和治疗骨髓增生异常综合征有用。
UNLABELLED Intramedullary apoptosis of hematopoietic tissue is believed to play a major role in the pathophysiology of myelodysplastic syndrome. Annexin V, a specific marker of the early to intermediate phases of apoptosis, has been applied to the in vitro study of bone marrow aspirates. A noninvasive measure of intramedullary apoptosis in vivo that could serially monitor the clinical progression of myelodysplastic syndrome may be helpful. METHODS We used 99mTc-radiolabeled annexin V and radionuclide gamma camera imaging to serially study the sites, extent, and severity of intramedullary apoptosis induced by cyclophosphamide treatment. RESULTS Intravenously administered radiolabeled annexin V localized preferentially in the femur, pelvis, vertebrae, and spleen; increased uptake in these organs was easily visualized as early as 8 h after injection of 100 mg/kg cyclophosphamide in 8- to 10-wk-old animals. Higher doses of cyclophosphamide (150 mg/kg) in animals of the same age increased annexin V uptake in the bone marrow and splenic tissue and delayed recovery of these organs as seen histologically compared with lower doses. Older animals, 5-6 mo old, showed a slower response to cyclophosphamide treatment and delayed recovery of bone marrow and splenic tissues. CONCLUSION Radiolabeled annexin V can be used to detect and directly quantify the degree of intramedullary and splenic apoptosis in a noninvasive fashion using current clinical radionuclide imaging equipment. Annexin V imaging may be useful clinically in the diagnosis and management of myelodysplastic syndrome.