1 Radiopharmaceuticals Division, Bhabha Atomic Research Centre , Mumbai, India .
Cancer Biother Radiopharm. 2013 Dec;28(10):737-45. doi: 10.1089/cbr.2013.1475. Epub 2013 Aug 9.
Thulium-170 [T1/2=128.4 days, Eβ(max)=968 keV, and Eγ=84 keV (3.26%)] could be considered an easily producible and cost-effective alternative to (89)Sr for the preparation of radiopharmaceuticals for palliation of bone pain arising due to skeletal metastases. Multidentate aminomethylene polyphosphonic acids have already been proven to be effective as carrier moieties for developing radiolabeled bone pain palliation agents using lanthanide radionuclides. Therefore, an attempt was made to evaluate the potential of a series of (170)Tm-labeled acyclic (diethylenetriaminepentamethylene phosphonic acid and triethylenetetraminehexamethylene phosphonic acid) and cyclic polyaminopolyphosphonic acids (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetramethylene phosphonic acid [DOTMP] and 1,4,8,11-tetraazacyclotetradecane-1,4,8,11-tetramethylene phosphonic acid [CTMP]) toward their use as alternative bone pain palliation agents.
Thulium-170 was produced by irradiating the natural Tm2O3 target at a thermal neutron flux of 7×10(13) n·cm(-2)·s(-1) for a period of 60 days. All the phosphonic acid ligands were synthesized and characterized in-house. The protocols for radiolabeling the phosphonic acids with (170)Tm were standardized. Biological evaluation of the (170)Tm-labeled phosphonic acids were carried out in normal Wistar rats by biodistribution as well as by scintigraphic studies.
Thulium-170 was produced with adequate specific activity (173 Ci/g, 6.41 TBq/g) and high radionuclidic purity (99.62%). All the (170)Tm-labeled phosphonic acids, except (170)Tm-CTMP, were prepared with very high radiochemical purity (>98%) under optimized reaction conditions and exhibited high stability. All the agents showed selective skeletal accumulation with insignificant uptake in other vital organs/tissues and major clearance through renal pathway. These findings were also substantiated by scintigraphic studies.
Although all the (170)Tm-labeled phosphonic acids showed significant and selective skeletal accumulation, radiochemical studies indicate that (170)Tm-DOTMP is the best choice for carrying out further evaluation toward its use for clinical applications.
铥-170（T1/2=128.4 天，Eβ(max)=968keV，Eγ=84keV（3.26%））可被视为一种易于制备且具有成本效益的替代物，可用于制备放射性药物，以缓解因骨骼转移引起的骨痛。多齿亚氨基甲基多膦酸已被证明是一种有效的载体部分，可用于使用镧系放射性核素开发放射性标记的骨痛缓解剂。因此，尝试评估一系列（170）Tm 标记的无环（二亚乙基三胺五亚甲基膦酸和三亚乙基四胺六亚甲基膦酸）和环状多氨基多膦酸（1,4,7,10-四氮杂环十二烷-1,4,7,10-四亚甲基膦酸[DOTMP]和 1,4,8,11-四氮杂环十四烷-1,4,8,11-四亚甲基膦酸[CTMP]）在作为替代骨痛缓解剂方面的潜力。
通过在热中子通量为 7×10（13）n·cm（-2）·s（-1）的条件下辐照天然 Tm2O3 靶 60 天，生产铥-170。所有膦酸配体均在内部合成并进行了表征。标准化了用（170）Tm 标记膦酸的方案。通过生物分布和闪烁照相研究，在正常 Wistar 大鼠中进行了（170）Tm 标记的膦酸的生物学评价。
铥-170 的比活度（173Ci/g，6.41TBq/g）和放射性核纯度（99.62%）均达到足够高的水平。在优化的反应条件下，除（170）Tm-CTMP 外，所有（170）Tm 标记的膦酸均以非常高的放射化学纯度（>98%）制备，并表现出很高的稳定性。所有制剂均表现出选择性的骨骼蓄积，其他重要器官/组织的摄取量微不足道，主要通过肾脏途径清除。闪烁照相研究也证实了这些发现。
尽管所有（170）Tm 标记的膦酸均显示出显著且选择性的骨骼蓄积，但放射化学研究表明，（170）Tm-DOTMP 是进一步评估其用于临床应用的最佳选择。
