DEVELOPEMENT OF RADIOIODINATED RADIOPHARMACEUTICALS FOR INTERNAL RADIATION THERAPY OF TUMOR BASED ON ITS SPECIFIC METABOLIC ACTIVITY

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The aim of this study is to develop a new radiopharmaceutical labeled with radioiodine for detection and therapy of tumors, which has affinity to a characteristic metabolism in tumor. 3-Iodo-4-hydroxyphenyl-L-cysteine (I-L-PC), as we have reported previously, was found to have an interaction for tyrosinase, an essential and rate-limiting enzyme to melanin biosynthesis. In this study, considering higher affinity for tyrosinase, we synthesized 3-iodo-4-hydroxyphenylcysteamine (I-PCA) that was an amine derivative of I-L-PC and examined biodistribution study in melanoma-bearing mice.4-Hydroxyphenylcysteamine (4-PCA) was synthesized and radioiodinated in our laboratory. I-PCA was prepared by conventional chloramine-T method under no-carrier added condition. The biodistribution of I-PCA in B16 melanoma-bearing C57BL6 mice showed rapid blood clearance, renal excretion and low accumulation in normal tissue. The results suggested that I-PCA achieved the desired affinity for melanin formation. T … More hat is, I-PCA has high potentiality for diagnosis of malignant melanoma. Moreover, because I-PCA accumulated low in normal tissue and showed rapid clearance, it might be applied as a therapeutic radiopharmaceutical when labeled with I-131.Approximately 70 % of I-IMP, a cerebral blood flow agent, is bound to serum protein. If the binding of radiopharmaceutical 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-IMP and several binding displacers was evaluated to improve cerebral imaging. The free fraction rate of I-IMP was increased up to 1.2 times of control with 6MNA, a clinically available HSA site II displacer. In monkey scintigraphic study, cerebral accumulation was significantly accelerated. Indeed, 6MNA treatment increased free I-IMP in monkey serum. Since the displacement method could easily be applied to human study, the competitive displacement can control tissue distribution and kinetics of radiopharmaceuticals in clinical application. Less