Basic and Clinical Studies on Imaging for Tumor and Inflammatory Lesion by Ga-67 and In-111

本研究旨在探讨Ga-67在恶性肿瘤及炎性病变中的蓄积机制。通过对结构中中性糖的测定，确定肿瘤中与ga -67结合的主要酸性粘多糖为硫酸角蛋白和/或聚硫酸角蛋白。另一方面，从粘多糖酶处理的结果可以明确肿瘤中主要结合Ga-67的酸性粘多糖不是硫酸角蛋白、硫酸肝素、肝素，也不是硫酸软骨素A、B、c。根据目前的结果，可以推断肿瘤中主要结合Ga-67的酸性粘多糖是角蛋白聚硫酸，并且这种酸性粘多糖在Ga-67的肿瘤积累中起着最重要的作用。注射松节油后，炎症灶中Ga-67的摄取率随时间增加而增加，5天后达到平稳期，此时病变的摄取率高于其他组织。放射自显像观察显示，与嗜中性粒细胞和巨噬细胞浸润的皮下组织相对应，Ga-67大量积聚，该核素在这些细胞周围的细胞间集中。生化研究表明，Ga-67与病变中的酸性粘多糖（角蛋白聚硫酸酯等）结合。另一方面，病变的毛细血管通透性远高于正常组织。基于目前的结果，我们认为Ga-67进入炎性病变的机制如下：炎性病变中Ga-67的积累主要是由于Ga-67通过通透性增加的毛细血管渗漏到有中性粒细胞和巨噬细胞浸润的皮下组织。在炎性病变中，Ga-67优先与构成细胞间物质的酸性粘多糖（角蛋白聚硫酸酯等）结合。

This study was undertaken to investigate the mechanism of accumulation of Ga-67 in the malignant tumor and the inflammatory lesion. It was determined from measuring neutral saccharide in the structure that the principal Ga-67-binding acid mucopolysaccharide in the tumor was keratan sulfate and/or keratan polysulfate. On the other hand, it was clarified from the results of mucopolysaccharase treatment that the main Ga-67-binding acid mucopolysaccharide in tumor was not keratan sulfate, heparan sulfate, heparin, nor chondroitin sulfate A,B,or C. Based on the present results, it was deduced that the main Ga-67-binding acid mucopolysaccharide in tumor is keratan polysulfate and that this acid mucopolysaccharide plays the most important role in tumor accumulation of Ga-67.The uptake rate of Ga-67 in the inflammatory lesion was increased with time after injection of turpentine oil and reached a plateau five days later, and at this time the rate for the lesion was larger than those for any other tissues. From the observation by autoradiography, it was revealed that Ga-67 was avidly accumulated corresponding to the subcutaneous tissue infiltrated with neutrophils and macrophages, and this nuclide was concentrated intercellularly around these cells. And it became clear from biochemical study that Ga-67 was bound to the acid mucopolysaccharide (keratan polysulfate, etc.) in the lesion. On the other hand, capillary permeability in this lesion was much greater than that of normal tissues.based on the present results, mechanisms of Ga-67 uptake into inflammatory lesion are concluded as follows:accumulation of Ga-67 in the inflammatory lesion is primarily due to leakage of Ga-67 into the subcutaneous tissue infiltrated with neutrophils and macrophages through capillaries with increased permeability. In the inflammatory lesion, Ga-67 is preferentially bound to the acid mucopolysaccharides(keratan polysulfate, etc.) which compose intercellular substances.