188Re—HEDP治疗肿瘤骨转移痛药代动力学研究

目的研究188Re标记的1-羟基-1，1-二膦酸钠乙烷（即依替膦酸盐，HEDP）在肿瘤骨转移患者体内的分布和排泄，分析不同剂量188Re—HEDP在患者体内的药代动力学特点。方法将40例肿瘤骨转移患者分为4组，每组10例，4组分别按体质量“弹丸”式经肘静脉注射188Re—HEDP20，30，40和50MBq／kg，给药时及给药后1，2，4，5，12，24，36，48，60和72h分别用SPECT仪采集胸前区和前后位、后前位全身图像，并收集患者尿液，测量放射性。利用感兴趣区（ROI）技术在左心室区测得经本底校正的放射性，作为血液放射性。将1h全身前位、后位放射性总计数率经死时间和时间衰减校正后的几何平均值设定为100％注射剂量（ID），据此估算上述各时间点全身和各器官的百分注射剂量率（％ID）。各组间的计量资料采用元、中位数、范围等表示，组间比较采用方差分析或t检验。结果20～50MBq／kg范围内，188Re—HEDP在体内的时间-放射性曲线下面积（AUC）与其剂量呈线性关系，r^2=0．9376。4组均符合静脉给药二室模型，AUC值中位数分别为3．32×10^5，3．97×10^5，7．83×10^5，8．58×10^5；分布速度常数（α值）中位数分别为0．06，0．05，0．04，0．06；消除速度常数（B值）中位数分别为1．16×10^-3，1．16×10^-3，1．03×10^-3，1．15×10^-3；指数项系数A值中位数分别为3591．21，4858．23，5642．48，4167．05；指数项系数B值中位数分别为293．97，352．95，614．41，1063．82；药物分布相半衰期T1/2值中位数分别为12．51，12．83，15．41，12．02min；药物消除相半衰期T1／2（β）中位数分别为595．47，596．50，673．09，600．93min。骨组织是摄取188Re—HEDP的主要组织，给药后4h放射性摄取高，约为40％ID，其他组织未见明显摄取188Re—HEDP0188Re．HEDP主要通过泌尿系统排泄，给药后24h排出66．79％ID，其中74％在给药后5h内排出。结论20～50MBq／kg范围内，188Re—HEDP在机体内的药代动力学符合血管给药二室模型。188Re—HEDP T1/2（β）平均为616．50min。188Re—HEDP主要通过泌尿系统排泄；骨组织是摄取188Re—HEDP的主要组织。

Pharmacokinetics of 188Re-HEDP in cancer patients with osseous metastases

Objective To investigate the biodistribution,excretion and other pharmacokinetics,of 188Re-1-hydroxy-1,1-ethylidene disodium phosphonate (HEDP) in cancer patients with osseous metastases who were suffering form bone pain. Methods A single dose (20,30,40,and 50 MBq/kg,10 patients in every group) of 188Re-HEDP was administered as a bolus injection,meanwhile dynamic images on patient's chest were collected for 30 min. Anterior and posterior whole-body images were obtained at 1,2,4,5,12,24,36,48,60 and 72 h after injection of 188Re-HEDP. By region of interest (ROI) technology,the curve of time-background corrected counts of left cardiac ventricle could be generated,and the background-corrected counts of various organs and total whole body could be calculated as a geometric mean using the anterior and posterior scans,and transformed to the percentage injected dose ( % ID). Urine was collected after injection of 188Re-HEDP. Counts of urine were measured by γ counter. Analysis of variance and t-test were used. Results Linear relationship of metabolism of 188Re-HEDP was observed in the doses from 20 to 50 MBq/kg,with correlation coefficient r2 = 0. 9376. A two-compartment model was the best fit for metabolism of 188Re-HEDP with the parameters median area under curve (AUC) 3.32 × 105,3.97 × 105,7.83 × 105,8.58 ×105,respectively; median α 0.06,0.05,0.04,0.06 respectively; median β 1.16 ×10-3,1.16 × 10-3,1.03 × 10-3,1.15 × 10 -3 respectively; median A 3591.21,4858.23,5642. 48,4167.05 respectively; median B 293.97,352.95,614.41,1063.82 respectively; median T1/2(α) 12.51,12.83,15.41,12.02 min respectively; median T1/2(β) 595.47,596.50,673.09,600.93 min respectively in the doses of 20,30,40and 50 MBq/kg. 188Re-HEDP was taken up mainly by bone up to 40% ID at 4 h. Urine profile showed that 66.79 % ID was eliminated within 24 h,being its 74% collected along the first 5 h after-administration.Conclusions In the doses of 20,30,40 and 50 MBq/kg,metabolism of 188Re-HEDP presented linear model. Pharmacokinetics of 188 Re-HEDP followed a two-compartment model administrated by blood vessel.Following injection,188 Re-HEDP was taken up mainly by bone and excreted by uropoietic system.