Modeling of the renal kinetics of the AT1 receptor specific PET radioligand [11C]KR31173.
Modeling of the renal kinetics of the AT1 receptor specific PET radioligand [11C]KR31173.
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DOI：
10.1155/2013/835859
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发表时间：
2013
影响因子：
--
通讯作者：
Szabo Z
中科院分区：
文献类型：
--
作者：
Gulaldi NC;Xia J;Feng T;Hong K;Mathews WB;Ruben D;Kamel IR;Tsui BM;Szabo Z
目的。放射性配体[11C]KR31173已被引入用于血管紧张素II亚型1受体(AT1R)的PET成像。本研究的目的是在猪肾缺血再灌流(IR)模型中应用和验证一个隔室模型来定量该放射性配基的动力学。程序。本研究包括10头家猪，其中5头为对照组，5头为左肾IR的试验组。为了达到IR，用球囊插入左肾动脉造成急性缺血，并充气60分钟。再通通过放气和取出球囊来实现。IR后1周测定血生化、尿比重、尿液PH值、肾素血管紧张素系统循环激素，并行PET显像。从90 分钟[11C]KR31173动态正电子发射计算机断层扫描获得的皮质时间-活动曲线用包含平行连接的两个组织隔室的隔室模型处理。将由放射性配基保留率(80 最小值与最大值之比)量化的放射性配基结合与由隔室模型得出的结合参数进行比较。结合比计算为DVR=DVS/DVNS，其中DVS和DVNS表示特异性结合和非特异性结合的分布体积。体外放射自显影测定受体结合力。结果。通过卷积和去卷积曲线拟合得到的结合参数与速率常数之间的相关性显著(r>；0.9)。从组织活动曲线得到的保留参数(Y Ret)和从脉冲响应函数得到的保留参数(F Ret)之间的相关性也很显著。此外，这两个保留参数与DVR之间存在显著的相关性。PET测量表明，IR对放射性配基结合参数没有显著影响，这些体内发现得到了体外放射自显影的证实。结论。各种绑定参数之间的相关性支持并行连接区模型的概念。如果不能获得动脉输入功能，简单的放射性配基保留可能足以估计体内放射性配基结合。
Purpose. The radioligand [11C]KR31173 has been introduced for PET imaging of the angiotensin II subtype 1 receptor (AT1R). The purpose of the present project was to employ and validate a compartmental model for quantification of the kinetics of this radioligand in a porcine model of renal ischemia followed by reperfusion (IR). Procedures. Ten domestic pigs were included in the study: five controls and five experimental animals with IR of the left kidney. To achieve IR, acute ischemia was created with a balloon inserted into the left renal artery and inflated for 60 minutes. Reperfusion was achieved by deflation and removal of the balloon. Blood chemistries, urine specific gravity and PH values, and circulating hormones of the renin angiotensin system were measured and PET imaging was performed one week after IR. Cortical time-activity curves obtained from a 90 min [11C]KR31173 dynamic PET study were processed with a compartmental model that included two tissue compartments connected in parallel. Radioligand binding quantified by radioligand retention (80 min value to maximum value ratio) was compared to the binding parameters derived from the compartmental model. A binding ratio was calculated as DVR = DVS/DVNS, where DVS and DVNS represented the distribution volumes of specific binding and nonspecific binding. Receptor binding was also determined by autoradiography in vitro. Results. Correlations between rate constants and binding parameters derived by the convolution and deconvolution curve fittings were significant (r > 0.9). Also significant was the correlation between the retention parameter derived from the tissue activity curve (Y ret) and the retention parameter derived from the impulse response function (f ret). Furthermore, significant correlations were found between these two retention parameters and DVR. Measurements with PET showed no significant changes in the radioligand binding parameters caused by IR, and these in vivo findings were confirmed by autoradiography performed in vitro. Conclusions. Correlations between various binding parameters support the concept of the parallel connectivity compartmental model. If an arterial input function cannot be obtained, simple radioligand retention may be adequate for estimation of in vivo radioligand binding.
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影响因子：
3.1
作者：
Mathews, WB;Yoo, SE;Szabo, Z
通讯作者：
Szabo, Z
DOI：
10.1007/s00259-007-0667-z
发表时间：
2008-06-01
影响因子：
9.1
作者：
Zober, Tamas G.;Fabucci, Maria Elena;Szabo, Zsolt
通讯作者：
Szabo, Zsolt
影响因子：
3.1
作者：
GIBSON, RE;BEAUCHAMP, HT;BURNS, HD
通讯作者：
BURNS, HD
DOI：
10.1137/0111030
发表时间：
1963-01-01
期刊：
JOURNAL OF THE SOCIETY FOR INDUSTRIAL AND APPLIED MATHEMATICS
影响因子：
--
作者：
MARQUARDT, DW
通讯作者：
MARQUARDT, DW
DOI：
10.1152/ajprenal.2000.279.4.f636
发表时间：
2000-10-01
影响因子：
4.2
作者：
Allred, AJ;Chappell, MC;Diz, DI
通讯作者：
Diz, DI