Amino K
Nihon Seikeigeka Gakkai Zasshi. 1982 Aug;56(8):765-76.
Tissue concentrations of methotrexate (MTX) in osteosarcomas were examined with special reference to their histologic findings. Primary tumors in five cases and metastatic tumors in two cases were removed at 6-18 days after MTX administration. The concentrations of MTX in osteosarcoma tissues were higher than those in normal tissues and serum, ranging from 15.0 to 168 ng/g. Necrotic portions of the tumor lesion were less in MTX concentration than cellular portions. As the cellularity increased, the tumor tissue showed higher MTX concentration. Tissue concentrations of MTX in nude mice with transplanted osteosarcoma from human were also studied after the high-dose 3H-MTX infusion. MTX total, which contains dihydrofolate reductase-bound MTX, free MTX and its metabolites, decreased gradually with time in the tumor tissues. The concentrations of MTX total in tumor were proportional to the administrated dose and the clearances of MTX were prolonged according to the dose-increase of MTX. Tissue concentrations of MTX total in the lung, kidney and liver were higher than that in tumor itself at 192 hours after the injection. The value for MTX total includes some MTX active fraction which can inhibit the activity of dihydrofolate reductase. Tissue concentrations of MTX active also increased dose-dependently. The proportions of MTX active to MTX total in tumors decreased with the increment of the MTX dose, and the same findings were observed in the kidney and liver.
以骨肉瘤组织学检查结果为特别参考，对甲氨蝶呤（MTX）在骨肉瘤中的组织浓度进行了检测。在给予MTX后6 - 18天，切除了5例原发性肿瘤和2例转移性肿瘤。骨肉瘤组织中MTX的浓度高于正常组织和血清，范围为15.0至168 ng/g。肿瘤病变的坏死部分MTX浓度低于细胞部分。随着细胞密度增加，肿瘤组织显示出更高的MTX浓度。在大剂量输注³H - MTX后，还对移植了人骨肉瘤的裸鼠的MTX组织浓度进行了研究。包含与二氢叶酸还原酶结合的MTX、游离MTX及其代谢产物的MTX总量，在肿瘤组织中随时间逐渐降低。肿瘤中MTX总量的浓度与给药剂量成正比，并且MTX的清除率随着MTX剂量的增加而延长。注射后192小时，肺、肾和肝中MTX总量的组织浓度高于肿瘤本身。MTX总量的值包括一些可抑制二氢叶酸还原酶活性的MTX活性部分。MTX活性的组织浓度也呈剂量依赖性增加。肿瘤中MTX活性占MTX总量的比例随MTX剂量的增加而降低，在肾和肝中也观察到了相同的结果。
