Roivainen Anne, Någren Kjell, Hirvonen Jussi, Oikonen Vesa, Virsu Pauliina, Tolvanen Tuula, Rinne Juha O
Turku PET Centre, Turku University Hospital, Turku, Finland.
Eur J Nucl Med Mol Imaging. 2009 Apr;36(4):671-82. doi: 10.1007/s00259-008-1000-1. Epub 2008 Dec 3.
(11)C-PK11195 is a radiopharmaceutical for in vivo assessment of peripheral benzodiazepine receptor (PBR) activity using PET. We sought to clarify the metabolic fate of (11)C-PK11195 in a test-retest setting using radio-HPLC in comparison with radio-TLC, and the whole-body distribution in humans.
In order to evaluate the reproducibility of radio-HPLC metabolite analyses, ten patients with Alzheimer's disease (AD) underwent two successive (11)C-PK11195 examinations on separate days. For comparison of different analytical methods, plasma samples from seven patients were also analysed by radio-TLC. In addition, we evaluated the whole-body distribution of (11)C-PK11195 and its uptake in the brain.
The level of unmetabolized (11)C-PK11195 decreased slowly from 96.3 +/- 1.6% (mean+/-SD) at 5 min to 62.7 +/- 8.3% at 40 min after injection. Large individual variation was observed in the amount of plasma (11)C-PK11195 radiometabolites. The whole-body distribution of (11)C-PK11195 showed the highest radioactivity levels in urinary bladder, adrenal gland, liver, salivary glands, heart, kidneys, and vertebral column. In addition, the hip bone and breast bone were clearly visualized by PET. In patients with AD, (11)C-PK11195 uptake in the brain was the highest in the basal ganglia and thalamus, followed by the cortical grey matter regions and the cerebellum. Low (11)C-PK11195 uptake was observed in the white matter.
Our results indicate that (11)C-PK11195 is eliminated both through the renal and hepatobiliary systems. Careful analysis of plasma metabolites is required to determine the accurate arterial input function for quantitative PET measurement.
（11）C-PK11195是一种用于通过正电子发射断层扫描（PET）体内评估外周苯二氮䓬受体（PBR）活性的放射性药物。我们试图在重测环境中使用放射性高效液相色谱法（radio-HPLC）并与放射性薄层色谱法（radio-TLC）比较，阐明（11）C-PK11195的代谢命运，以及其在人体中的全身分布。
为了评估radio-HPLC代谢物分析的可重复性，10名阿尔茨海默病（AD）患者在不同日期接受了两次连续的（11）C-PK11195检查。为了比较不同的分析方法，还对7名患者的血浆样本进行了radio-TLC分析。此外，我们评估了（11）C-PK11195的全身分布及其在脑中的摄取。
未代谢的（11）C-PK11195水平从注射后5分钟时的96.3±1.6%（平均值±标准差）缓慢下降至40分钟时的62.7±8.3%。观察到血浆中（11）C-PK11195放射性代谢物的量存在较大个体差异。（11）C-PK11195的全身分布显示膀胱、肾上腺、肝脏、唾液腺、心脏、肾脏和脊柱的放射性水平最高。此外，通过PET清晰地观察到髋骨和胸骨。在AD患者中，（11）C-PK11195在脑中的摄取在基底神经节和丘脑最高，其次是皮质灰质区域和小脑。在白质中观察到（11）C-PK11195摄取较低。
我们的结果表明，（11）C-PK11195通过肾和肝胆系统消除。为了确定用于定量PET测量的准确动脉输入函数，需要仔细分析血浆代谢物。
