Amyloid plaque imaging agent [C-11]-6-OH-BTA-1:: biodistribution and radiation dosimetry in baboon
Amyloid plaque imaging agent [C-11]-6-OH-BTA-1:: biodistribution and radiation dosimetry in baboon
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DOI：
10.1097/00006231-200510000-00005
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发表时间：
2005-10-01
影响因子：
1.5
通讯作者：
Mann, J. John
中科院分区：
文献类型：
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作者：
Parsey, Ramin V.;Sokol, Levi O.;Mann, J. John
背景：淀粉样神经炎斑块被认为是阿尔茨海默病患者脑组织中发现的淀粉样β蛋白的有毒集合。淀粉样蛋白结合硫代黄素-T(BTA)的一个中性类似物，已被放射性标记为[C-11]-6-OH-BTA-1。它可以穿过血脑屏障，是一种很有前途的示踪剂，可以用正电子发射断层扫描技术在体内对斑块进行成像。我们现在报道[C-111-6-OH-BTA-1在狒狒体内的生物分布和剂量学。方法在ECAT Accel相机上采集了4次2小时的全身研究，观察了[C-11]-6-OH-BTA-1团注后的情况。在注射前对每个床位进行3.5分钟的传输扫描后，在五个床位上以2-D模式收集发射扫描。脑、左右肺、心、肝、胆、左肾、右肾、脾和膀胱周围绘制感兴趣区(ROI)。由于没有从狒狒身上带走液体，所以使用注射剂量和从圆柱体模型确定的校准系数来计算全身放射性。每个ROI的曲线下面积(AUC)由前几个点与随后的点按递减的单指数曲线进行梯形积分来确定。然后将AUC除以全身计数，得到的停留时间被输入MIRDOSE3程序。该配体通过肝胆和肾系统被消除。在成年男性和女性参照物中，胆囊受到的辐射剂量最高，是关键器官(分别为3.9E-02mGyMBq和4.3E-02mGyMBq)。结论在美国，经放射性药物研究委员会(RDRC)批准，[C-11]-6-OH-BTA-1在成年男性和成年女性中的单次注射剂量分别为1295MBq(35MCI)和1314MBq(35MCI)。
Background The amyloid neuritic plaque is considered to be a toxic collection of amyloid-beta protein found in brain tissue in Alzheimer's disease. A neutral analogue of the amyloid-binding thioflavin-T (BTA), has been radiolabeled as [C-11]-6-OH-BTA-1. It crosses the blood brain barrier, and is a promising tracer for imaging plaques in vivo using positron emission tomography. We now report the biodistribution and dosimetry of [C-111-6-OH-BTA-1 in baboons.Methods Four 2-hour whole body studies were acquired in an ECAT ACCEL camera in two baboons after the bolus injection of [C-11]-6-OH-BTA-1. After 3.5 minute transmission scans performed per bed position prior to injection, emission scans were collected in 2-D mode over five bed positions. Regions of interest (ROI) were drawn around the brain, left and right lungs, heart, liver, gall bladder, left and right kidneys, spleen and urinary bladder. Since no fluid was removed from the baboons, total body radioactivity was calculated using the injected dose and a calibration factor determined from a cylinder phantom. The area under the curve (AUC) for each ROI was determined by trapezoidal integration of the first few points with subsequent points fit by a decreasing monoexponential. The AUC was then divided by counts in the total body, and resulting residence times were entered into the MIRDOSE3 program.Results The animals tolerated the procedure well. The ligand was eliminated via the hepatobiliary and renal systems. In the adult male and female reference the gallbladder received the highest estimated radiation dose and was the critical organ (3.9E-02 mGy/M Bq and 4.3E-02 mGy/M Bq respectively).Conclusion In the United States, the absorbed dose to the gallbladder would limit [C-11]-6-OH-BTA-1 administered with the approval of a Radioactive Drug Research Committee (RDRC) to a single injection of 1295 MBq (35 mCi) in the adult male, and 1314 M Bq (35 mCi) in the adult female.