^(13)N-NH_3·H_2O动物体内分布及临床应用

Pharmacological experiment of ^(13)N-ammonia as PET imaging agent

目的 研究1 3 N NH3 ·H2 O的临床前药理、PET显像方法及其在心肌显像中的应用。方法 进行犬全身和动态心肌PET显像 ,测定1 3 N NH3 ·H2 O在犬体内的分布 ,并对健康志愿者进行心肌PET显像。结果 心肌PET显像发现 ,心脏和肺是首过器官 ,心肌摄取率最高。心肌摄取快而清除相对较慢 ,血、肝和肺的本底清除快 ,心脏影像清晰。注射1 3 N NH3 ·H2 O后 30s,左右心室放射性达到峰值 ,1min后开始下降 ,在 4～ 2 0min保持相对平稳的水平 ;左心室间壁和侧壁心肌在注射后 10s开始摄取 ,间壁摄取高于侧壁 ,2min后侧壁摄取略高于间壁 ;肝和肺在第 30s摄取达峰值 ,此后急剧下降 ,5min后摄取逐渐下降并维持在较低的水平 ,心 肝和心 肺比值均高于 2 0。动物全身显像发现 ,1 3 N NH3 ·H2 O主要分布在血液供应丰富的组织 ,主要经肾脏清除。动态心肌显像和注射1 3 N NH3 ·H2 O 4～ 5min后进行的静态显像可获得一致的心肌血流灌注图像。结论 1 3 N NH3 ·H2 O有较高的心 肝和心 肺比值 ,灌注图像清晰 ,是理想的心肌血流灌注显像剂。

Objective To study the pharmacological characteristics of 13 N-ammonia, the clinical PET imaging methods of 13 N-ammonia, and its application in myocardial blood flow perfusion. Methods The uptakes of 13 N-ammonia in the myocardium and other organs in dogs were measured by whole body scanning and chest dynamic PET scanning. The regional myocardial blood flow (rMBF) in healthy volunteers was also measured by the dynamic and static PET imaging following intravenous bolus administration of 13 N-ammonia. Results The heart and lungs were the first-pass organs that was found out by PET imaging with 13 N-ammonia in dogs and human volunteers, the highest uptake of 13 N-ammonia in the myocardium was also observed. At 30 s after injection the radioactivity in the blood pool of left and right ventricles reached its peak, at 1 min it began to drop, and at 4～20 min after injection the lower radioactivity was kept on. Regional analysis of PET imaging showed that the myocardial uptake of 13 N-ammonia began at 10 s after injection, and the uptake in the septum wall was higher than that in the lateral wall; but in the septum wall was slightly higher than in the lateral wall at 2 min after injection. The radioactivity in the liver and lungs reached its peak at 30 s and was sharply declined hereafter. The uptake of 13 N-ammonia in the liver and lungs remained at the lower levels and the heart-to-blood, heart-to-liver and heart-to-lung ratios were above 2.0 after 5 min. Whole-body PET scanning for dogs showed that 13 N-ammonia was distributed primarily in the organs with rich blood flow and its clearance was observed in the kidney. The images of regional myocardial blood flow (rMBF) acquired from the dynamic or static PET imaging following intravenous bolus administration of 13 N-ammonia were of no difference. Conclusions The analysis of distribution of 13 N-ammonia indicates that the heart-to-blood, heart-to-liver and heart-to-lung ratios were high and the PET images were clear. 13 N-ammonia is an ideal myocardial blood flow perfusion imaging agent. rMBF can be measured accurately and noninvasively by 13 N-ammonia dynamic and static PET imaging.