Dormehl I C, Louw W K, Schneeweiss F H, Milner R, Schmitt G, Carl U, Croft S A
AEC Institute for Life Sciences, Medical Faculty, University of Pretoria, South Africa.
Arzneimittelforschung. 1998 Apr;48(4):408-14.
Palliation of bone pain in patients with bone metastases has previously been evaluated using 153Sm (samarium) complexed to bone seeking ethylenediamine tetramethylene phosphonic acid (CAS 1429-50-1, EDTMP). Repeated application of the radioligand as needed was found progressively less effective. This study questions whether EDTMP exerts a blocking function, limiting access to bone or osseous tumours with successive administration. The pharmacokinetics and biodistribution of 153Sm-EDTMP in the normal experimental baboon (n = 6) during three successive applications (6 weekly) each with two different concentrations of EDTMP (0.7 and 1.4 mg/kg b.wt.) were investigated using bone scintigraphy. 153Sm-EDTMP (111 MBq) was injected in each case and monitored for 5 h. Curves of tracer kinetics and bone to background uptake were obtained, also blood and cumulative urine curves. Comparisons were statistically assessed in each group between successive applications and between EDTMP concentrations. Partial blocking with the low EDTMP concentration reached statistical significance after the third application. The first application of the high EDTMP concentration yielded lower uptake in the bone than did low EDTMP pointing to blocking by the high concentration, but not seen with repeated applications. Continual application of high concentration EDTMP could lead to a reduced level of calcium in serum and increased parathyroid hormone levels which might trigger osteoblastic activity and bone remodelling. This would partially affect the blocking which was thus more obvious at the low EDTMP concentration.
先前曾使用与趋骨性乙二胺四亚甲基膦酸（化学物质登记号1429 - 50 - 1，EDTMP）络合的153Sm（钐）来评估骨转移患者的骨痛缓解情况。结果发现，根据需要重复应用放射性配体的效果逐渐降低。本研究质疑EDTMP是否发挥了阻断作用，随着连续给药，限制了对骨骼或骨肿瘤的摄取。使用骨闪烁显像技术，研究了正常实验狒狒（n = 6）在连续三次应用（每6周一次）、每次使用两种不同浓度的EDTMP（0.7和1.4 mg/kg体重）时153Sm - EDTMP的药代动力学和生物分布情况。每种情况下均注射153Sm - EDTMP（111 MBq）并监测5小时。获得了示踪剂动力学曲线以及骨与本底摄取曲线，还有血液和累积尿液曲线。对每组连续应用之间以及EDTMP浓度之间的比较进行了统计学评估。低浓度EDTMP的部分阻断作用在第三次应用后达到统计学显著性。高浓度EDTMP首次应用时在骨骼中的摄取低于低浓度EDTMP，表明高浓度存在阻断作用，但在重复应用时未观察到这种情况。持续应用高浓度EDTMP可能导致血清钙水平降低和甲状旁腺激素水平升高，这可能引发成骨细胞活性和骨重塑。这将部分影响阻断作用，因此在低浓度EDTMP时更为明显。
