Bayouth J E, Macey D J, Kasi L P, Garlich J R, McMillan K, Dimopoulos M A, Champlin R E
Department of Radiation Physics, University of Texas M.D. Anderson Cancer Center, Houston, USA.
J Nucl Med. 1995 May;36(5):730-7.
In this Phase I clinical trial, six multiple myeloma patients who had not responded to conventional therapy and were scheduled for bone marrow transplantation received a bone-seeking radiopharmaceutical for bone marrow ablation. The pharmacokinetics, dosimetry, and toxicity of this radiopharmaceutical were studied.
Patients received from 519 mCi to 2.1 Ci (19.2 GBq to 77.7 GBq) of holmium-166 (166Ho) complexed with a bone-seeking agent, DOTMP (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetramethylene-phosphonic acid). The reproducibility of pharmacokinetics from multiple injections of 166Ho-DOTMP administered to these myeloma patients was demonstrated from blood (r2 = 0.926) and whole-body retention (r2 = 0.983), which allowed therapeutic parameters to be determined from a diagnostic study.
Over 50% of the 166Ho-DOTMP injected dose was excreted within 2-3 hr postinjection, increasing to 75%-85% over a 24-hr period. Rapid blood clearance minimized radiation dose to nontarget tissue: less than 10% of the injected activity was retained in the blood pool at 1 hr postinjection, and less than 2% remained after 5 hr. The total radiation absorbed dose delivered to the bone marrow for the six patients ranged from 7.9 Gy to 41.4 Gy.
All patients demonstrated severe bone marrow toxicity with a white blood cell (WBC) count < 1,000 cells/microliters, two patients exhibited marrow ablation (WBC count < 100 cells/microliters), and no other toxicity > or = grade 2 was observed in any of the patients.
在这项I期临床试验中，6名对传统疗法无反应且计划进行骨髓移植的多发性骨髓瘤患者接受了一种亲骨性放射性药物用于骨髓消融。研究了该放射性药物的药代动力学、剂量学和毒性。
患者接受了519毫居里至2.1居里（19.2吉贝可至77.7吉贝可）与亲骨性试剂DOTMP（1,4,7,10 - 四氮杂环十二烷 - 1,4,7,10 - 四亚甲基膦酸）络合的钬 - 166（166Ho）。对这些骨髓瘤患者多次注射166Ho - DOTMP后的药代动力学重现性在血液（r2 = 0.926）和全身滞留（r2 = 0.983）方面得到了证明，这使得能够从诊断研究中确定治疗参数。
注射的166Ho - DOTMP剂量的50%以上在注射后2 - 3小时内排出，24小时内增加到75% - 85%。快速的血液清除使非靶组织的辐射剂量最小化：注射后1小时血液池中保留的注射活性小于10%，5小时后小于2%。6名患者骨髓接受的总辐射吸收剂量范围为7.9戈瑞至41.4戈瑞。
所有患者均表现出严重的骨髓毒性，白细胞（WBC）计数<1000个细胞/微升，两名患者出现骨髓消融（WBC计数<100个细胞/微升），且在任何患者中均未观察到其他≥2级的毒性。
