Knox S J, Levy R, Miller R A, Uhland W, Schiele J, Ruehl W, Finston R, Day-Lollini P, Goris M L
Department of Radiation Oncology, Stanford University Medical Center, California 94305.
Cancer Res. 1990 Aug 15;50(16):4935-40.
The murine B-cell lymphoma 38C13 model was used to study the radiobiological effect of 131I-monoclonal antibody (MAB) therapy compared with dose equivalent external beam irradiation. Continuous exponentially decreasing low dose rate (LDR) gamma-irradiation, and multiply fractionated (MF) X-irradiation were compared with dose equivalent 131I-MAB. The relative therapeutic efficacy of radioimmunotherapy, and the relative contribution of (a) low dose rate; (b) whole body irradiation; and (c) microdosimetry to the overall effect were determined. Groups of mice with or without B-cell lymphoma were treated with either (a) 131I-anti-idiotype MAB; (b) 131I-isotype-matched irrelevant control MAB; (c) 5-15 Gy 250 kV X-irradiation given as a single fraction; (d) 2.5-30 Gy 250 kV X-irradiation given in 10 fractions/2 weeks; or by (e) continuous exponentially decreasing gamma-irradiation via a 137Cs source, which simulated the effective t1/2 of the 131I-MAB. In tumor-free mice the LD50/30 was approximately 10 Gy for MF and LDR external irradiation, and 11-12 Gy for 131I-MAB. However, the effect of these modes of irradiation on tumor size differed significantly. The cumulative percentage of tumor reduction averaged over 12 days was 0.635 +/- 0.055%/Gy for MF, and 1.36 +/- 0.061%/Gy for LDR external irradiation (a relative efficacy factor of 1.63 for LDR irradiation; P = 0.01). Assuming homogeneous body distribution, the tumor reduction effect over 12 days for 131I-MAB was 2.064 +/- 0.133%/Gy for specific, and 1.742 +/- 0.1%/Gy for nonspecific isotype-matched irrelevant 131I-MAB (P = 0.02). When 131I-MAB was compared to LDR external irradiation, the relative efficacy factor was 1.99 (P less than 0.001). In summary, there was a dose rate effect on tumor response, which may in part explain the efficacy of radioimmunotherapy. The additional effect of 131I-MAB on tumor response was only partially explained by the cumulative concentration ratio of 131I-MAB tumor/131I-MAB whole body, which was on average 1.7. This relatively low concentration ratio was partly due to tumor-mediated dehalogenation. Thus, the overall tumor response was a function of the total dose, dose rate, and both the specific and nonspecific distribution of 131I-MAB.
采用鼠B细胞淋巴瘤38C13模型，研究131I单克隆抗体（MAB）治疗与等效剂量外照射的放射生物学效应。将连续指数递减低剂量率（LDR）γ照射和分次（MF）X照射与等效剂量的131I-MAB进行比较。确定了放射免疫治疗的相对疗效，以及（a）低剂量率；（b）全身照射；和（c）微剂量测定对总体效应的相对贡献。对有或无B细胞淋巴瘤的小鼠组进行以下处理：（a）131I抗独特型MAB；（b）131I同型匹配无关对照MAB；（c）单次给予5 - 15 Gy 250 kV X照射；（d）每2周分10次给予2.5 - 30 Gy 250 kV X照射；或（e）通过137Cs源进行连续指数递减γ照射，模拟131I-MAB的有效t1/2。在无肿瘤小鼠中，MF和LDR外照射的LD50/30约为10 Gy，131I-MAB为11 - 12 Gy。然而，这些照射方式对肿瘤大小的影响差异显著。MF照射12天内肿瘤缩小的累积百分比平均为0.635±0.055%/Gy，LDR外照射为1.36±0.061%/Gy（LDR照射的相对疗效因子为1.63；P = 0.01）。假设全身分布均匀，131I-MAB在12天内对特异性肿瘤缩小效应为2.064±0.133%/Gy，非特异性同型匹配无关131I-MAB为1.742±0.1%/Gy（P = 0.02）。当将131I-MAB与LDR外照射比较时，相对疗效因子为1.99（P＜0.001）。总之，存在剂量率对肿瘤反应的影响，这可能部分解释了放射免疫治疗的疗效。131I-MAB对肿瘤反应的额外效应仅部分由131I-MAB肿瘤/131I-MAB全身的累积浓度比解释，该比值平均为1.7。这种相对较低的浓度比部分归因于肿瘤介导的脱卤作用。因此，总体肿瘤反应是总剂量、剂量率以及131I-MAB特异性和非特异性分布的函数。
