Ohira H, Kubota K, Ohuchi N, Harada Y, Fukuda H, Satomi S
Second Department of Surgery, Tohoku University School of Medicine, Sendai, Japan.
J Nucl Med. 2000 Sep;41(9):1561-8.
The aims of this study were to evaluate the distribution of 99mTc-methoxyisobutylisonitrile (MIBI) in 3 animal models of breast cancer, the effect of radiotherapy on 99mTc-MIBI uptake, and the relationship between uptake and microvessel density.
We used syngeneic, subcutaneously transplanted FM3A, MM48, and Ehrlich mouse breast cancer. 99mTc-MIBI and FDG were injected intravenously, and tumor uptake was measured 30 min later. Double-tracer macroautoradiography (ARG) images were prepared with 99mTc-MIBI and 2-deoxy-D-[1-14C]-glucose (14C-DG), analyzed quantitatively, and compared with histology. The radiotherapeutic effects of 20 Gy x-ray irradiation were monitored by measuring tumor volume, tumor uptake, and ARG findings using 99mTc-MIBI and FDG in FM3A tumors. Microvessel density was quantified by immunohistochemical staining for CD34 and compared with ARG using 99mTc-MIBI in FM3A tumors.
FM3A, MM48, and Ehrlich tumors showed different growth rates and radiosensitivities. Uptake of FDG, but not of 99mTc-MIBI, correlated significantly with growth rates. Compared with 14C-DG, 99mTc-MIBI accumulated more in cancer cells and less in infiltrating fibroblasts and macrophages in all tumor models. Irradiation significantly decreased 99mTc-MIBI uptake, but a rapid increase was noted at recurrence on day 7. Changes in FDG uptake were not significant at recurrence. Microvessel density in tumor tissue correlated significantly with 99mTc-MIBI uptake on ARG.
Accumulation of 99mTC-MIBI in cancer cells is preferential and can be used as a sensitive marker to examine the response to radiotherapy. Angiogenesis seems to enhance accumulation of 99mTc-MIBI in tumors. These characteristics may be favorable for tumor imaging using 99mTC-MIBI.
本研究的目的是评估99mTc-甲氧基异丁基异腈（MIBI）在3种乳腺癌动物模型中的分布、放疗对99mTc-MIBI摄取的影响以及摄取与微血管密度之间的关系。
我们使用了同基因的、皮下移植的FM3A、MM48和艾氏小鼠乳腺癌。静脉注射99mTc-MIBI和FDG，30分钟后测量肿瘤摄取。用99mTc-MIBI和2-脱氧-D-[1-14C]-葡萄糖（14C-DG）制备双示踪剂宏观放射自显影（ARG）图像，进行定量分析，并与组织学进行比较。通过测量FM3A肿瘤的肿瘤体积、肿瘤摄取以及使用99mTc-MIBI和FDG的ARG结果来监测20 Gy X射线照射的放射治疗效果。通过对CD34进行免疫组织化学染色来定量微血管密度，并与FM3A肿瘤中使用99mTc-MIBI的ARG进行比较。
FM3A、MM48和艾氏肿瘤显示出不同的生长速率和放射敏感性。FDG的摄取与生长速率显著相关，但99mTc-MIBI的摄取与生长速率无关。与14C-DG相比，在所有肿瘤模型中，99mTc-MIBI在癌细胞中积累更多，在浸润的成纤维细胞和巨噬细胞中积累更少。照射显著降低了99mTc-MIBI的摄取，但在第7天复发时发现摄取迅速增加。复发时FDG摄取的变化不显著。肿瘤组织中的微血管密度与ARG上99mTc-MIBI的摄取显著相关。
99mTc-MIBI在癌细胞中的积累具有优先性，可作为检测放疗反应的敏感标志物。血管生成似乎增强了99mTc-MIBI在肿瘤中的积累。这些特性可能有利于使用99mTc-MIBI进行肿瘤成像。
