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

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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