Pharmacokinetic modelling of N-(4-[(18)F]fluorobenzoyl)interleukin-2 binding to activated lymphocytes in an xenograft model of inflammation.
Pharmacokinetic modelling of N-(4-[(18)F]fluorobenzoyl)interleukin-2 binding to activated lymphocytes in an xenograft model of inflammation.
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DOI：
10.1007/s00259-012-2176-y
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发表时间：
2012-10
影响因子：
9.1
通讯作者：
de Vries, Erik F. J.
中科院分区：
文献类型：
--
作者：
Di Gialleonardo, Valentina;Signore, Alberto;Willemsen, Antoon T. M.;Sijbesma, Jurgen W. A.;Dierckx, Rudi A. J. O.;de Vries, Erik F. J.
N-(4-[18F]氟苯甲酰基)白介素2([18F]FB-IL2)与白介素2受体(IL-2R)特异性结合，可用于正电子发射断层扫描(PET)检测炎症过程。我们现在通过药代动力学模型验证了[18F]FB-IL2是否可以用于在大鼠体内定量激活的人外周血单个核细胞(HPBMC)。11只Wistar大鼠于静脉注射前15分钟在肩部皮下接种不同剂量的植物血凝素(PHA)激活的hPBMC。注射[18F]FB-IL2。采集60min动态正电子发射计算机断层扫描，并进行动脉采血和代谢物分析。扫描结束后，动物被终止，炎性病变被解剖。使用Logan和Patlak分析以及单组织和两组织间隔模型对PET数据进行分析。根据Akaike信息标准(AIC)评估模型偏好以及PET测量和CD25阳性细胞数量之间的相关性。移植瘤的体外示踪剂摄取量(标化摄取值)与接种的CD2 5阳性细胞数高度相关(R2 = 0.90)。血浆时间-活动曲线显示放射性药物从血液中迅速洗出，而炎性病变的时间-活动曲线显示洗出较慢。用Logan分析方法可以很好地拟合时间-活性曲线，表明[18F]FB-IL2与CD25的结合是可逆的。AIC指出，数据可以用两组织可逆室模型模拟得最好。结合势与CD2 5阳性细胞数高度相关(R2 = 0.876，p <； 0.0001)。根据正电子发射计算机断层扫描测量的结合电位，其检测下限约为每200个μL病变中约160,000个CD25阳性细胞(95%置信度)。[18F]在这种炎症动物模型中，FB-IL2的动力学可以用可逆的两组织室模型来描述。[18F]FB-IL2结合电位是准确定量PET病理条件下淋巴细胞浸润的一种合适的方法。本文的在线版本(doi：10.1007/s00259-0122176-y)包含补充材料，授权用户可以使用。
N-(4-[18F]Fluorobenzoyl)interleukin-2 ([18F]FB-IL2) specifically binds to interleukin-2 receptors (IL-2R) and thus may be used to detect inflammation processes using positron emission tomography (PET). We now validated whether [18F]FB-IL2 can be used to quantify activated human peripheral blood mononuclear cells (hPBMC) in rats by pharmacokinetic modelling. Eleven Wistar rats were subcutaneously inoculated in the shoulder with different amounts of phytohaemagglutinin (PHA) activated hPBMC 15 min before i.v. injection of [18F]FB-IL2. A 60-min dynamic PET scan was acquired and arterial blood sampling and metabolite analysis were performed. At the end of the scan, animals were terminated and the inflammatory lesion dissected. PET data were analysed using Logan and Patlak analysis as well as one-tissue and two-tissue compartment models. Model preferences according to the Akaike information criterion (AIC) and correlation between PET measurements and the number of CD25-positive cells were evaluated. A high correlation between ex vivo tracer uptake (standardized uptake value) in the xenograft and the number of inoculated CD25-positive cells was observed (R 2 = 0.90). Plasma time-activity curves showed a rapid washout of the radiopharmaceutical from blood, while the time-activity curves of the inflammatory lesions showed slower washout. Time-activity curves could be fitted well by the Logan analysis method, indicating that the binding between [18F]FB-IL2 and CD25 is reversible. AIC indicated that data could be modelled best by a two-tissue reversible compartment model. A high correlation was observed between the binding potential and the number of CD25-positive cells (R 2 = 0.876, p < 0.0001). Based on binding potential measured by PET, the limit of detection was about 160,000 CD25-positive cells per 200 μl lesion (95 % confidence). [18F]FB-IL2 kinetics in this animal model of inflammation could be best described by a reversible two-tissue compartment model. The [18F]FB-IL2 binding potential is a suitable measure for accurate quantification of lymphocytic infiltration in pathological conditions with PET. The online version of this article (doi:10.1007/s00259-012-2176-y) contains supplementary material, which is available to authorized users.
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影响因子：
13.1
作者：
Singh, Tushar;Newman, Anne B.
通讯作者：
Newman, Anne B.
DOI：
10.1111/j.1365-2133.2011.10507.x
发表时间：
2011-11
期刊：
The British journal of dermatology
影响因子：
--
作者：
Rangwala S;Tsai KY
通讯作者：
Tsai KY
影响因子：
3.1
作者：
Chianelli, M;Signore, A;Mather, SJ
通讯作者：
Mather, SJ
DOI：
10.1073/pnas.0708594105
发表时间：
2008-01-15
影响因子：
11.1
作者：
Swann, Jeremy B.;Vesely, Matthew D.;Smyth, Mark J.
通讯作者：
Smyth, Mark J.
影响因子：
3.1
作者：
D'Alessandria, Calogero;di Gialleonardo, Valentina;Signore, Alberto
通讯作者：
Signore, Alberto