Comparison of [(11)C]-(R)-PK 11195 and [(11)C]PBR28, two radioligands for translocator protein (18 kDa) in human and monkey: Implications for positron emission tomographic imaging of this inflammation biomarker.
Comparison of [(11)C]-(R)-PK 11195 and [(11)C]PBR28, two radioligands for translocator protein (18 kDa) in human and monkey: Implications for positron emission tomographic imaging of this inflammation biomarker.
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DOI：
10.1016/j.neuroimage.2009.11.056
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发表时间：
2010-02-15
期刊：
影响因子：
5.7
通讯作者：
Innis, Robert B.
中科院分区：
文献类型：
--
作者：
Kreisl, William C.;Fujita, Masahiro;Fujimura, Yota;Kimura, Nobuyo;Jenko, Kimberly J.;Kannan, Pavitra;Hong, Jinsoo;Morse, Cheryl L.;Zoghbi, Sami S.;Gladding, Robert L.;Jacobson, Steven;Oh, Unsong;Pike, Victor W.;Innis, Robert B.
10%的人缺乏[11C]PBR28与18 kDa转位蛋白(TSPO)的特异性结合，TSPO是炎症的生物标志物。尽管另一种TSPO放射性配体[11C]-(R)-PK 11195已经使用了20多年，但尚未有使用该配体的报告。这项研究提出了两个问题：1)PBR28不结合的原因是什么？2)为什么[11C]-(R)-PK 11195没有报道这种现象？5个粘结剂和5个非粘结剂接受了[11C]-(R)-PK 11195和[11C]PBR28的全身成像。体外结合使用来自粘合剂和非粘合剂的白细胞膜以及配基的氚版本。用[11C]-(R)-PK 11195在基线和阻断TSPOS后对恒河猴进行显像。使用[11C]PBR28，非粘结剂中TSPO高密度的所有五个器官(肺、心、脑、肾和脾)的摄取量比粘结剂中低50%至75%。相比之下，[11C]-(R)-PK 11195仅在心脏和肺区分粘结剂和非粘结剂。在体外试验中，[~3H]PBR28在非粘结剂中对TSPO的亲和力比在粘结剂中低10倍以上。[11C]-(R)-PK 11195在猴脑中的体内特异性结合比文献报道的[11C]-(R)-PK 11195低80倍。基于[~3H]PK 11195与白细胞膜的结合，结合蛋白和非结合蛋白都表达TSPO。与PBR28的非结合是由于其在非粘结剂中对TSPO的低亲和力造成的。非结合蛋白可能在人体各器官中有不同的表达。[11C]-(R)-PK 11195在体内的特异性结合相对较低，可能掩盖了它在外周器官中检测到的非结合。
Ten percent of humans lack specific binding of [11C]PBR28 to 18 kDa translocator protein (TSPO), a biomarker for inflammation. “Non-binders” have not been reported using another TSPO radioligand, [11C]-(R)-PK 11195, despite its use for more than two decades. This study asked two questions: 1) What is the cause of non-binding to PBR28? 2) Why has this phenomenon not been reported using [11C]-(R)-PK 11195? Five binders and five non-binders received whole-body imaging with both [11C]-(R)-PK 11195 and [11C]PBR28. In vitro binding was performed using leukocyte membranes from binders and non-binders and the tritiated versions of the ligand. Rhesus monkeys were imaged with [11C]-(R)-PK 11195 at baseline and after blockade of TSPOs. Using [11C]PBR28, uptake in all five organs with high densities of TSPO (lung, heart, brain, kidney, and spleen) was 50% to 75% lower in non-binders than in binders. In contrast, [11C]-(R)-PK 11195 distinguished binders and non-binders in only heart and lung. For the in vitro assay, [3H]PBR28 had more than ten-fold lower affinity to TSPO in non-binders than in binders. The in vivo specific binding of [11C]-(R)-PK 11195 in monkey brain was ∼80-fold lower than that reported for [11C]PBR28. Based on binding of [3H]PK 11195 to leukocyte membranes, both binders and non-binders express TSPO. Non-binding to PBR28 is caused by its low affinity for TSPO in non-binders. Non-binding may be differentially expressed in organs of the body. The relatively low in vivo specific binding of [11C]-(R)-PK 11195 may have obscured its detection of non-binding in peripheral organs.
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影响因子：
--
作者：
Calcagno AM;Chewning KJ;Wu CP;Ambudkar SV
通讯作者：
Ambudkar SV
影响因子：
5.7
作者：
Imaizumi, Masao;Briard, Emmanuelle;Fujita, Masahiro
通讯作者：
Fujita, Masahiro
影响因子：
5.7
作者：
Henrich, Curtis J.;Robey, Robert W.;McMahon, James B.
通讯作者：
McMahon, James B.
影响因子：
9.3
作者：
Brown, Amira K.;Fujita, Masahiro;Innis, Robert B.
通讯作者：
Innis, Robert B.
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y