Hauck M L, Larsen R H, Welsh P C, Zalutsky M R
Department of Pathology, Duke University Medical Center, Durham, NC 27710, USA.
Br J Cancer. 1998 Mar;77(5):753-9. doi: 10.1038/bjc.1998.123.
The high linear energy transfer, alpha-particle-emitting radionuclide astatine-211 (211At) is of interest for certain therapeutic applications; however, because of the 55- to 70-microm path length of its alpha-particles, achieving homogeneous tracer distribution is critical. Hyperthermia may enhance the therapeutic efficacy of alpha-particle endoradiotherapy if it can improve tracer distribution. In this study, we have investigated whether hyperthermia increased the cytotoxicity of an 211At-labelled monoclonal antibody (MAb) in tumour spheroids with a radius (approximately 100 microm) greater than the range of 211At alpha-particles. Hyperthermia for 1 h at 42 degrees C was used because this treatment itself resulted in no regrowth delay. Radiolabelled chimeric MAb 81C6 reactive with the extracellular matrix antigen tenascin was added to spheroids grown from the D-247 MG human glioma cell line at activity concentrations ranging from 0.125 to 250 kBq ml(-1). A significant regrowth delay was observed at 125 and 250 kBq ml(-1) in both hyperthermia-treated and untreated spheroids. For groups receiving hyperthermia, no increase in cytotoxicity was seen compared with normothermic controls at any activity concentration. These results and those from autoradiographs indicate that hyperthermia at 42 degrees C for 1 h had no significant effect on the uptake or distribution of this antitenascin MAb in D-247 MG spheroids.
高传能线密度、发射α粒子的放射性核素砹-211（²¹¹At）在某些治疗应用中具有吸引力；然而，由于其α粒子的路径长度为55至70微米，实现示踪剂的均匀分布至关重要。如果热疗能够改善示踪剂分布，那么它可能会增强α粒子内放射治疗的疗效。在本研究中，我们调查了热疗是否会增加²¹¹At标记的单克隆抗体（MAb）在半径（约100微米）大于²¹¹At α粒子射程的肿瘤球体中的细胞毒性。使用42℃热疗1小时，因为这种治疗本身不会导致再生长延迟。将与细胞外基质抗原腱生蛋白反应的放射性标记嵌合单克隆抗体81C6以0.125至250 kBq ml⁻¹的活性浓度添加到由D-247 MG人胶质瘤细胞系生长的球体中。在125和250 kBq ml⁻¹时，热疗处理和未处理的球体均观察到明显的再生长延迟。对于接受热疗的组，在任何活性浓度下与常温对照组相比均未观察到细胞毒性增加。这些结果以及放射自显影片的结果表明，42℃热疗1小时对这种抗腱生蛋白单克隆抗体在D-247 MG球体中的摄取或分布没有显著影响。
