Šimeček Jakub, Hermann Petr, Seidl Christof, Bruchertseifer Frank, Morgenstern Alfred, Wester Hans-Jürgen, Notni Johannes
Lehrstuhl für Pharmazeutische Radiochemie, Technische Universität München,, Walther-Meißner-Strasse 3, 85748, Garching, Germany.
Present address: Isotope Technologies Garching GmbH, Garching, Germany.
EJNMMI Res. 2018 Aug 8;8(1):78. doi: 10.1186/s13550-018-0431-3.
The recently growing interest in targeted alpha-therapy (TAT) calls for improvement of the labelling chemistry of the corresponding radionuclides. Bi is a short-lived alpha emitter which emits only one alpha particle in its decay chain. Hence, it might be safer in application than other respective nuclides, such as Ra or Ac, because no alpha-emitting daughters are released upon recoil. We investigated cyclen derivatives with phosphorus-containing pendant arms regarding their suitability for Bi labelling.
The concentration dependency of Bi labelling at 25 °C and 95 °C was determined for DOTP, DOTP, DOTP, and DOTPI, as well as for DOTA and CHX-A"-DTPA for comparison. The labelling efficiency of the phosphorus-containing ligands was at least comparable to CHX-A"-DTPA and exceeded that of DOTA. DOTP was most efficient, requiring chelator concentrations for labelling which were approx. two orders of magnitude lower than those required for CHX-A"-DTPA, both at 25 °C and 95 °C. The Bi complexes of phosphorus ligands furthermore showed a higher stability against demetallation (> 96% of intact complex after 120-min incubation in plasma were found for DOTP, DOTP, and DOTP, compared to 85% for DOTA and 76% for CHX-A"-DTPA).
Cyclen derivatives bearing four N-methylenephosphonic or -phosphinic acid substituents, e.g., DOTP, are capable of complexing the alpha-emitting radionuclide Bi with higher efficiency and in-vitro stability than the current gold standards DOTA and CHX-A"-DTPA.
近期对靶向α治疗（TAT）的兴趣日益增长，这就需要改进相应放射性核素的标记化学。铋是一种短寿命α发射体，在其衰变链中仅发射一个α粒子。因此，与其他相应的核素（如镭或锕）相比，它在应用中可能更安全，因为反冲时不会释放出α发射子体。我们研究了带有含磷侧链的轮环化合物用于铋标记的适用性。
测定了DOTP、DOTP、DOTP和DOTPI在25℃和95℃下铋标记的浓度依赖性，同时测定了DOTA和CHX-A”-DTPA作为比较。含磷配体的标记效率至少与CHX-A”-DTPA相当，且超过了DOTA。DOTP效率最高，在25℃和95℃下，其标记所需的螯合剂浓度比CHX-A”-DTPA所需浓度低约两个数量级。此外，磷配体的铋配合物对脱金属表现出更高的稳定性（在血浆中孵育120分钟后，DOTP、DOTP和DOTP的完整配合物含量>96%，而DOTA为85%，CHX-A”-DTPA为76%）。
带有四个N-亚甲基膦酸或次膦酸取代基的轮环化合物衍生物，如DOTP，能够比目前的金标准DOTA和CHX-A”-DTPA更高效地络合发射α粒子的放射性核素铋，并具有更高的体外稳定性。
