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在恶性肿瘤和炎性病变中蓄积的机制。从测量结构中的中性糖确定，肿瘤中主要的Ga-67结合酸性粘多糖是硫酸角质素和/或多硫酸角质素。另一方面，从粘多糖酶处理的结果可以清楚地看出，肿瘤中主要的Ga-67结合酸性粘多糖不是硫酸角质素、硫酸乙酰肝素、肝素，也不是硫酸软骨素A、B或C。根据以上结果，推测肿瘤中主要的Ga-67结合酸性粘多糖是多硫酸角质素，这种酸性粘多糖在Ga-67的肿瘤蓄积中起着最重要的作用。注射松节油后，炎症病变中Ga-67的摄取率随时间增加，5天后达到平台，并且此时病变的速率大于任何其它组织的速率。通过放射自显影观察，发现Ga-67与浸润有嗜中性粒细胞和巨噬细胞的皮下组织相对应地大量积聚，并且该核素在这些细胞周围的细胞间浓缩。生化研究表明Ga-67与酸性粘多糖（多硫酸角质素等）结合。在病变中。另一方面，在这个病变中的毛细血管渗透性比正常组织的大得多。根据本研究结果，Ga-67摄取到炎性病变中的机制如下：Ga-67在炎性病变中的积聚主要是由于Ga-67通过具有增加的渗透性的毛细血管渗漏到浸润有中性粒细胞和巨噬细胞的皮下组织中。在炎性病变中，Ga-67优先结合于酸性粘多糖（多硫酸角质素等）。它们组成细胞间物质。

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.