Development of Selective Localized Hyperthermia for Deep Seated Cancer with Magnetic Seramic Microspheres.

空心铁磁微球比致密的铁磁微球更适合于癌症的热疗，因为前者很难在血管中沉淀。在九州工业大学，研究了空心磁铁矿微球的制备。将氢氧化铁溶胶分散在不与水混溶的2-乙基- 1 -己醇中制备乳液。将氢氧化铁溶胶脱水，在丁醇中凝胶化，过滤得到的粉末，然后在真空中进行不同温度的热处理。得到了直径为10 ~ 100 μm的微球。直径大于100 μm的微球大部分被破坏，而直径小于50 μm的微球没有被破坏。粉末x射线衍射证实，在800℃、1000℃和1150℃热处理后，形成赤铁矿、赤铁矿与磁铁矿的混合物和磁铁矿。通过对微球截面的扫描电镜观察，证实微球是空心的。本年度的研究结果表明，采用本方法可以成功制备出直径为20-30 μm的空心磁铁矿微球，适用于癌症热疗。我们将铁磁微球注射到兔肾中，并证实了局部加热。组织学检查，微球在肾组织内均匀分布。虽然在兔肝注射中检测到肝酶的暂时升高，但未检测到主要的不良反应。我们在实验过程中证实了注射到小猎犬肝脏的可行性。我们研制的铁磁微球安全可靠，具有良好的临床应用前景。我们在京都大学放射肿瘤学治疗学系开发了一种自动注射系统。使用喷射器，微球可以缓慢注入，以相同的速度，没有溢出。

Hollow ferrimagnetic microspheres are more suitable for hyperthermia of cancer than dense ones, since the former is hard to sediment in blood vessels. In Kyushu Institute of Technology, preparation of hollow magnetite microspheres was examined. Emulsion was prepared where iron hydroxide sol was dispersed in 2-ethyl-l-hexanol that are immiscible with water. The iron hydroxide sol was gelled in butanol by dehydration of the sol. The obtained powders were filtered and then subjected to heat treatments at different temperatures in vacuo. Microspheres ranging 10 to 100 μm in diameter were obtained. Most of the microspheres over 100 μm in diameter was broken, but not those under 50 μm in diameter. It was confirmed by powder X-ray diffraction that hematite, mixture of hematite and magnetite, and magnetite was formed by the heat treatment at 800, 1000 and 1150℃, respectively. The formed microspheres were confirmed to be hollow by SEM observation of their cross-sections. The results in this year show that hollow magnetite microspheres 20-30 μm in diameter suitable for the hyperthermia of cancer can be successfully obtained by the present method.We injected the ferrimagnetic microspheres into the rabbit kidney, and confirmed the local heating. In histological evaluation, the microspheres were uniformly distributed in renal tissue. Although temporary elevation of hepatic enzymes was detected, but no major adverse effect was detected in the rabbit's liver injections. We confirmed the feasibility of the injection into the beagle liver in the experimental procedures. Our ferrimagnetic microspheres appear safe and promising, and clinical application is highly encouraged. And we developed an automatic injection system in Department of Therapeutic Radiology ＆ Oncology, Kyoto University. Using the injector, the microsphere can be slowly injected, at same speed without overflow.