Venkataraman Ashwin V, Keat Nicholas, Myers James F, Turton Samuel, Mick Inge, Gunn Roger N, Rabiner Eugenii A, Passchier Jan, Parker Christine A, Tyacke Robin J, Nutt David J
Neuropsychopharmacology Unit, Centre for Psychiatry, Division of Brain Sciences, Imperial College London, 5th Floor Burlington Danes Building, Hammersmith Hospital campus, 160 Du Cane Road, London, W12 0NN, UK.
Restorative Neurosciences, Imperial College London, Burlington Danes Building, Hammersmith Hospital campus, 160 Du Cane Road, London, W12 0NN, UK.
EJNMMI Res. 2018 Jul 30;8(1):71. doi: 10.1186/s13550-018-0429-x.
We measured whole body distribution of C-BU99008, a new PET biomarker for non-invasive identification of the imidazoline binding site. The purpose of this phase I study was to evaluate the biodistribution and radiation dosimetry of C-BU99008 in healthy human subjects.
A single bolus injection of C-BU99008 (296 ± 10.5 MBq) was administered to four healthy subjects who underwent whole-body PET/CT over 120 min from the cranial vertex to the mid-thigh. Volumes of interest were drawn around visually identifiable source organs to generate time-activity curves (TAC). Residence times were determined from time-activity curves. Absorbed doses to individual organs and the whole body effective dose were calculated using OLINDA/EXM 1.1 for each subject.
The highest measured activity concentration was in the kidney and spleen. The longest residence time was in the muscle at 0.100 ± 0.023 h, followed by the liver at 0.067 ± 0.015 h and lungs at 0.052 ± 0.010 h. The highest mean organ absorbed dose was within the heart wall (0.028 ± 0.002 mGy/MBq), followed by the kidneys (0.026 ± 0.005 mGy/MBq). The critical organ was the heart wall. The total mean effective dose averaged over subjects was estimated to be 0.0056 ± 0.0004 mSv/MBq for an injection of C-BU99008.
The biodistribution of C-BU99008 has been shown here for the first time in humans. Our dosimetry data showed the total mean effective dose over all subjects was 0.0056 ± 0.0004 mSv/MBq, which would result in a total effective dose of 1.96 mSv for a typical injection of 350 MBq of C-BU99008. The effective dose is not appreciably different from those obtained with other C tracers.
我们测量了C-BU99008在全身的分布情况，C-BU99008是一种用于非侵入性识别咪唑啉结合位点的新型正电子发射断层显像（PET）生物标志物。这项I期研究的目的是评估C-BU99008在健康人体受试者中的生物分布和辐射剂量学。
对4名健康受试者单次静脉注射C-BU99008（296±10.5MBq），并在120分钟内从颅顶至大腿中部进行全身PET/CT检查。在视觉上可识别的源器官周围绘制感兴趣区以生成时间-活度曲线（TAC）。根据时间-活度曲线确定驻留时间。使用OLINDA/EXM 1.1为每个受试者计算各个器官的吸收剂量和全身有效剂量。
测得的最高活度浓度出现在肾脏和脾脏。最长驻留时间出现在肌肉，为0.100±0.023小时，其次是肝脏，为0.067±0.015小时，肺部为0.052±0.010小时。平均器官吸收剂量最高的是心壁（0.028±0.002mGy/MBq），其次是肾脏（0.026±0.005mGy/MBq）。关键器官是心壁。对于注射C-BU99008，所有受试者的平均总有效剂量估计为0.0056±0.0004mSv/MBq。
C-BU99008的生物分布在此首次在人体中得到展示。我们的剂量学数据显示，所有受试者的平均总有效剂量为0.0056±0.0004mSv/MBq，这意味着典型的350MBq C-BU99008注射的总有效剂量为1.96mSv。该有效剂量与其他碳示踪剂获得的有效剂量没有明显差异。
