The use of technetium Tc 99m annexin V for in vivo imaging of apoptosis during cardiac allograft rejection.

The use of technetium Tc 99m annexin V for in vivo imaging of apoptosis during cardiac allograft rejection.
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使用锝 Tc 99m 膜联蛋白 V 对心脏同种异体移植排斥过程中的细胞凋亡进行体内成像。

DOI:
10.1016/s0022-5223(98)00446-2
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发表时间:
1998
期刊:
The Journal of thoracic and cardiovascular surgery
影响因子:
--
通讯作者:
Robbins,RC
Robbins,RC
中科院分区:
--
文献类型:
--
作者:
Vriens,PW;Blankenberg,FG;Stoot,JH;Ohtsuki,K;Berry,GJ;Tait,JF;Strauss,HW;Robbins,RC

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目的细胞凋亡或程序性细胞死亡是同种异体心脏移植排斥反应中免疫损伤的一种机制。我们验证了用于检测细胞凋亡的新型放射性药物~(99m)Tc-Annexin V可用于核成像检测心脏移植排斥反应的假说。方法将未经处理的ACI大鼠作为同种异体PVG大鼠(n=66)和同基因ACI大鼠(n=30)心脏移植物的受体。未经处理的受体动物连续7天每天接受99mTC-Annexin V显像。用感兴趣区分析定量99mTC-Annexin V摄取,成像后立即获取移植物进行组织病理学分析和末端脱氧核苷酸转移酶介导的脱氧尿嘧啶核苷-生物素缺口末端标记凋亡核。一组于移植后第4天开始给予环孢素10 mg/kg/d治疗(n=6)。结果移植后第4天未处理的同种异体移植物出现排斥反应的组织学征象。所有排斥同种异体移植物的心肌细胞、内皮细胞和移植物浸润性细胞均可见凋亡细胞核。核成像显示,移植后第4天(P=.05)、第5天(P<.001)、第6天(P<.001)和第7天(P=.013),排斥同种异体移植物的99mTC-Annexin V摄取率显著高于同基因移植物。急性排斥反应的组织学分级与99mTC-Annexin V摄取呈正相关(R2=0.87)。用环孢素治疗排斥反应后,移植物内未见凋亡细胞核,99mTC-Annexin V摄取降至基线水平。结论心脏移植急性排斥反应时发生细胞凋亡,排斥反应治疗后细胞凋亡消失,99mTc-Annexin V可用于心脏移植排斥反应的检测和监测。(胸心外科杂志1998;116:844-53)
ObjectiveApoptosis, or programmed cell death, has been suggested as a mechanism of immunologic injury during cardiac allograft rejection. We tested the hypothesis that technetium Tc 99m annexin V, a novel radiopharmaceutical used to detect apoptosis, can be used to detect cardiac allograft rejection by nuclear imaging.MethodsUntreated ACI rats served as recipients of allogeneic PVG rat (n = 66) or syngeneic ACI rat (n = 30) cardiac grafts. Untreated recipient animals underwent99mTc-annexin V imaging daily for 7 days. Region of interest analysis was used to quantify the uptake of99mTc-annexin V. Immediately after imaging grafts were procured for histopathologic analysis and terminal deoxynucleotidyltransferase-mediated deoxyuridine triphosphate–biotin nick-end labeling of apoptotic nuclei. One group was treated with 10 mg/kg/d cyclosporine (INN: ciclosporin) commencing on day 4 after transplantation (n = 6).ResultsUntreated allografts showed histologic signs of rejection 4 days after transplantation. Apoptotic nuclei could be demonstrated in myocytes, endothelial cells, and graft-infiltrating cells of all rejecting allografts. Nuclear imaging revealed a significantly greater uptake of99mTc-annexin V in rejecting allogeneic grafts than in syngeneic grafts on day 4 (P = .05), day 5 (P < .001), day 6 (P < .001), and day 7 (P = .013) after transplantation. A correlation between the histologic grade of acute rejection and uptake of99mTc-annexin V was observed (r2= 0.87). After treatment of rejection with cyclosporine, no apoptotic nuclei could be identified in allografts and uptake of99mTc-annexin V decreased to baseline.ConclusionsApoptosis occurs during acute cardiac allograft rejection and disappears after treatment of rejection.99mTc-annexin V can be used to detect and monitor cardiac allograft rejection. (J Thorac Cardiovasc Surg 1998;116:844-53)
DOI: --
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DOI: --
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