APPLOCATION OF LUNG RECEPTOR IMAGING TO THERAPEUTIC DRUG MONITERING (FOUNDAMENTAL EVALUATION WITH ANIMAL POSITRON CT)

我们试图发展肺受体成像方法，以解决哮喘的机制，并为治疗药物监测提供有用的信息。测定放射性碘MIBG肺吸收的动物实验。使用I-131MIBG和Tc-99m HSA双示踪技术测量I-131MIBG的肺摄取，该技术需要取序贯动脉血液样本。本实验在豚鼠中显示约30%的MIBG肺摄取，其摄取呈剂量依赖性。我们还开发了计算机软件来测量肺部对放射性标记受体配体的摄取，而不需要血液采样数据。放射性示踪剂雾化吸入技术的动物实验。用扫描技术研究了雾化MIBG在肺中的药代动力学。提示主要结合药物的受体的位置与给药路线有关。高分辨率动物PET动物实验。我们生产了C-11吡咯胺作为H1受体的配体，并获得了95%的化学纯化。用C-11吡咯胺成功地获得了豚鼠的肺图像，但这种放射性药物的质量控制问题仍然存在。

We have tried to develop the method of lung receptor imaging which may sesolve the mechanism of asthma and give useful information regarding to therapeautic drug monitering.1. Animal experiment to measure the lung uptake of radioiodine MIBG.The lung uptake of I-131 MIBG has been measured using dual tracer technique with I-131MIBG and Tc-99m HSA, which needed to take sequential arterial blood samples. About 30% of MIBG lung uptake was shown in this experiment using guinea pigs and its uptake presented the dose dependency. We also develop the computer software to measure the lung uptake of radiolabeled receptor ligand without blood sampling data.2. Animal experiment with aerolized radiotracer inhalation technique.Pharmacokinetics of aerolized MIBG in the lung has been investigated with scintigraphic technique. It suggested that the location of receptor which mainly bind a drug depended on the rout of drug administration.3. Animal experiment with high resolution animal PET.We produced the C-11 pyrilamine as a ligand of H1 receptor and obtained 95% of chemical purify. We also succeeded to obtain the lung image of guinea pigs with C-11 pyrilamine but the problem of quality control of this radiopharrmaceutical has been remained.