DEVELOPMENT OF RADIOIODINATED RADIOPHARMACEUTICALS FOR FUNCTION DIAGNOSIS OF CEREBRAL NEURON AND THEIR MOLECULAR DESIGN.

l -间酪氨酸（L-mTyr）是儿茶酚胺（如多巴胺和肾上腺素）的前体，呈l型，其3位羟基是左旋多巴的最小结构，因此可能用作脑多巴胺能突触前功能的探针。L-mTyr通过手性高效液相色谱法从D， l -外消旋体中分离出来，用非载体介导的1-125标记。I-125-L-mTyr在大脑和胰腺中的积累量更高。它在大脑中的积累是立体特异性的，并且依赖于能量。抗脱碘，无滞留机制，排泄迅速。L-mTyr的直接放射性碘化产生两个几何异构体。6-[I-125]碘-和4-[I-125]碘- l -间酪氨酸（6- i - l - mtyr, 4- i - l - mtyr）采用反相高效液相色谱法分离。在生物分布研究中，6-I-L-mTyr倾向于保留在大脑中。它在大脑中的积累依赖于能量。在血液中，6-I-L-mTyr具有较高的活性，但也能迅速消除。NSD-1015仅能抑制6-I-L-mTyr在组织切片中的体外积累。结果表明，6-I-L-mTyr与多巴胺生物合成的最终酶——大脑芳香氨基酸脱羧酶（AADC）具有亲和力。这些发现也得到了体内抑制研究的证实。因此，6-I-L-mTyr是一种新的放射性药物，可用于评估脑氨基酸转运机制和量化代谢活性AADC。大约70%的I-123-IMP（一种脑血流剂）与血清蛋白结合。如果具有高蛋白结合亲和力的替代物能够抑制放射性药物与血清蛋白的结合，则可以增强该示踪剂的总清除率和组织分布。评估了I-123-IMP与几种结合取代物之间的相互作用，以改善大脑成像。超滤法测定血清蛋白结合情况。I-123-IMP的游离分数率增加到对照的1.2倍，6MNA是一种临床可用的HAS II位置换剂。大鼠生物分布表明，6MNA负载对I-123-IMP的清除速度更快。在猴子的脑电图研究中，大脑积累明显加快。确实，在猴子血清研究中，6MNA处理增加了游离I-123 IMP。由于位移法易于应用于人体研究，因此在临床应用中，I-123-IMP的竞争位移可以控制其组织分布和动力学。少

L-meta-Tyrosine (L-mTyr), a precursor of catecholamines such as dopamine and nor epinephrine, is in the L-form and it has a hydroxy group at 3-position as a minimum structure of L-DOPA therefore it could probably be used as a probe for the cerebral dopaminergic presynaptic function. L-mTyr separated from D, L-racemate by chiral HPLC, was labeled with non-carrier mediated 1-125. I-125-L-mTyr had a higher accumulation in the brain and the pancreas. Its accumulation in the brain is stereo specific and energy dependent. It was resistant to deiodination, had no retention mechanism and rapidly excreted.The direct radio iodination of L-mTyr produced two geometric isomers. 6-[I-125] iodo- and 4-[I-125] iodo-L-meta tyrosine (6-I-L-mTyr, 4-I-L-mTyr) were separated by reverse phase HPLC. In the biodistribution study, 6-I-L-mTyr had a tendency to be retained in the brain. Its accumulation in the brain was energy dependent. In the blood, 6-I-L-mTyr had higher activity but was also rapidly eliminate … More d. There were also high metabolic stability and rapid clearance through renal excretion. With in vitro accumulation in tissue slices, only the accumulation of 6-I-L-mTyr was inhibited by NSD-1015. It shows that 6-I-L-mTyr had an affinity to cerebral aromatic amino acid decarboxylase (AADC), the final enzyme of dopamine biosynthesis. These findings were also confirmed by in vivo inhibition study using auto radiography. Thus, it was shown that 6-I-L-mTyr is a new radio pharmaceutical that can be both useful in assessing cerebral amino acid transport mechanism and in quantifying metabolically active AADC.Approximately 70 % of I-123-IMP, a cerebral blood flow agent, is bound to serum protein. If the binding of radio pharmaceutical to serum protein can be inhibited by displacers with high protein binding affinity, the total clearance and tissue distribution of this tracer would be enhanced. The interaction between I-123-IMP and several binding displacers was evaluated to improve cerebral imaging. The serum protein binding was evaluated by ultra filtration. The free fraction rate of I-123-IMP was increased up to 1.2 times of control with 6MNA, a clinically available HAS site II displacer. The rat biodistribution showed more rapid clearance of I-123-IMP with 6MNA loading. In monkey scintigraphic study, cerebral accumulation was significantly accelerated. Indeed, 6MNA treatment increased free I-123 IMP in monkey serum study. Since the displacement method could easily be applied to human study, the competitive displacement of I-123-IMP can control their tissue distribution and kinetics in clinical application. Less