11C-WAY100,635在人体中的生物分布和辐射剂量测定

Biodistribution and radiation dosimetry of 11C-WAY100,635 in humans.

作者信息

Parsey Ramin V, Belanger Marie-Jose, Sullivan Gregory M, Simpson Norman R, Stabin Michael G, Van Heertum Ronald, Mann J John

机构信息

Division of Brain Imaging, Department of Neuroscience, New York State Psychiatric Institute, New York, New York, USA.

出版信息

J Nucl Med. 2005 Apr;46(4):614-9.

PMID:15809484

Abstract

UNLABELLED

Serotonin 1A receptors have been implicated in a variety of conditions including depression, suicidal behavior, and aggression. Dose estimates for current human studies are based on data from rat dosimetry studies. We report the biodistribution and dosimetry of the PET serotonin 1A antagonist 11C-WAY100,635 in humans.

METHODS

PET studies of 6 healthy human volunteers (3 male, 3 female) were acquired after a bolus injection of 11C-WAY100,635. Transmission scans of 3.5 min were obtained at each bed position before injection, and emission scans then were collected in 2-dimensional mode over 8 bed positions. Regions of interest were drawn around the brain, left and right lungs, heart, liver, stomach wall, gallbladder, left and right kidneys, spleen, and urinary bladder. Because no fluid was removed from the subjects, whole-body radioactivity was calculated using the injected dose and a calibration factor determined from a cylinder phantom. The area under the curve for each region of interest was determined by trapezoidal integration of the first 3 points, with subsequent points fit by a decreasing monoexponential. The area under the curve was then divided by counts in the whole body, and the resulting residence times were entered into the MIRDOSE3 program.

RESULTS

Primary elimination was via kidneys to the urinary bladder. There were no sex differences in organ residence times. The urinary bladder wall was the organ with the highest estimated radiation dose (1.94 x 10(-1) +/- 3.57 x 10(-2) mGy/MBq). Except for the kidney and bladder wall, correlation was good between human dosimetry estimates and estimates reported previously from rats. The human dosimetry was 6.6 and 60.6 times higher in the kidneys and urinary bladder wall, respectively, than estimates from rats.

CONCLUSION

The urinary bladder wall is the critical organ for 11C-WAY100,635 in humans. In the United States, according to Radioactive Drug Research Committee guidelines a single dose cannot exceed 300 MBq in a man and 227 MBq in a woman, with up to 3 such injections permitted per annum.

摘要

未标注

5-羟色胺1A受体与多种病症有关，包括抑郁症、自杀行为和攻击行为。目前人体研究的剂量估计是基于大鼠剂量测定研究的数据。我们报告了正电子发射断层扫描（PET）5-羟色胺1A拮抗剂11C-WAY100635在人体中的生物分布和剂量测定。

方法

对6名健康人类志愿者（3名男性，3名女性）进行PET研究，在静脉推注11C-WAY100635后进行扫描。在注射前，在每个床位进行3.5分钟的透射扫描，然后以二维模式在8个床位收集发射扫描图像。在大脑、左右肺、心脏、肝脏、胃壁、胆囊、左右肾、脾脏和膀胱周围绘制感兴趣区域。由于未从受试者身上抽取液体，因此使用注射剂量和由圆柱形体模确定的校准因子来计算全身放射性。通过对前3个点进行梯形积分来确定每个感兴趣区域的曲线下面积，随后的点用递减的单指数拟合。然后将曲线下面积除以全身计数，并将所得的停留时间输入MIRDOSE3程序。