Parks N J, Kawakami T G, Avila M J, White R, Cain G R, Raaka S D, Hornoff W, Fisher P, Moore P, Seibert J A
Institute for Toxicology and Environmental Health, University of California, Davis 95616.
Blood. 1993 Jul 1;82(1):318-25.
beta-emitting 166Ho (t1/2 = 26.78 hours, E(beta)max = 1.8 MeV) complexed with the phosphonic acid chelator, 1,4,7,10 tetraazacyclododecane-1,4,7,10-tetra(methylene phosphonic acid) (DOTMP) at a ligand-to-metal ratio of 1.5:1 binds to bone. This radioactive complex is a marrow-ablating radiopharmaceutical that appears useful for preparation of bone marrow (BM) transplant recipients without the morbidity usually associated with total body irradiation preparatory regimens. We have found with seven splenectomized young adult beagle dogs that a 166Ho radiopharmaceutical dosage of 370 MBq/kg body weight provides an initial skeletal radioactivity burden of at least 1.5 GBq/kg skeleton and results in complete ablation of hematopoietic marrow cell populations within 7 days. The beta particle flux distribution in BM-forming skeletal tissue is not uniform. Red marrow radiation doses varied from 30 to 115 Gy as estimated by direct radioassay and autoradiographic analyses of both bone biopsies and postmortem samples; the median value of 61 Gy agreed with our theoretical expectations. In vivo radioactivity distribution was evaluated with nuclear imaging methods. Apparently, normal hematopoiesis was restored in three dogs with autologous BM transplants performed 5 to 6 days after administration of the marrow ablative radiopharmaceutical, 166Ho-DOTMP. BM biopsies at 7 to 10 months posttransplantation indicate continued normal hematopoietic activity.
与膦酸螯合剂1,4,7,10-四氮杂环十二烷-1,4,7,10-四（亚甲基膦酸）（DOTMP）以1.5:1的配体与金属比例络合的发射β射线的166Ho（半衰期=26.78小时，最大β能量=1.8兆电子伏特）与骨结合。这种放射性络合物是一种骨髓消融放射性药物，似乎可用于制备骨髓移植受者，而不会出现全身照射预处理方案通常伴随的发病率。我们对7只脾切除的成年比格犬进行研究发现，166Ho放射性药物剂量为370兆贝可/千克体重时，初始骨骼放射性负荷至少为1.5吉贝可/千克骨骼，并在7天内导致造血骨髓细胞群完全消融。形成骨髓的骨骼组织中的β粒子通量分布不均匀。通过对骨活检和死后样本的直接放射性测定和放射自显影分析估计，红骨髓辐射剂量在30至115戈瑞之间；61戈瑞的中值与我们的理论预期相符。用核成像方法评估体内放射性分布。显然，在给予骨髓消融放射性药物166Ho-DOTMP后5至6天进行自体骨髓移植的3只犬中，正常造血功能得以恢复。移植后7至10个月的骨髓活检表明造血活动持续正常。
