体内分布
放射性核素治疗
化学
放射性配体
核医学
多塔
药代动力学
剂量学
医学
放射免疫疗法
药理学
耐受性
治疗指标
体外
癌症研究
免疫学
单克隆抗体
生物化学
抗体
药品
有机化学
螯合作用
不利影响
作者
Viviane J. Tschan,Sarah D Busslinger,Peter Bernhardt,Pascal V. Grundler,Jan Rijn Zeevaart,Ulli Köster,Nicholas P. van der Meulen,Roger Schibli,Cristina Müller
标识
DOI:10.2967/jnumed.123.265524
摘要
The favorable decay characteristics of 161Tb attracted the interest of clinicians in using this novel radionuclide for radioligand therapy (RLT). 161Tb decays with a similar half-life to 177Lu, but beyond the emission of β--particles and γ-rays, 161Tb also emits conversion and Auger electrons, which may be particularly effective to eliminate micrometastases. The aim of this study was to compare the dosimetry and therapeutic efficacy of 161Tb and 177Lu in tumor-bearing mice using SibuDAB and PSMA-I&T, which differ in their blood residence time and tumor uptake. Methods: [161Tb]Tb-SibuDAB and [161Tb]Tb-PSMA-I&T were evaluated in vitro and investigated in biodistribution, imaging, and therapy studies using PC-3 PIP tumor-bearing mice. The 177Lu-labeled counterparts served for dose calculations and comparison of therapeutic efficacy. The tolerability of RLT in mice was monitored on the basis of body mass, blood plasma parameters, blood cell counts, and the histology of relevant organs and tissues. Results: The prostate-specific membrane antigen (PSMA)-targeting radioligands, irrespective of whether labeled with 161Tb or 177Lu, showed similar in vitro data and comparable tissue distribution profiles. As a result of the albumin-binding properties, [161Tb]Tb/[177Lu]Lu-SibuDAB had an enhanced blood residence time and higher tumor uptake (62%-69% injected activity per gram at 24 h after injection) than [161Tb]Tb/[177Lu]Lu-PSMA-I&T (30%-35% injected activity per gram at 24 h after injection). [161Tb]Tb-SibuDAB inhibited tumor growth more effectively than [161Tb]Tb-PSMA-I&T, as can be ascribed to its 4-fold increased absorbed tumor dose. At any of the applied activities, the 161Tb-based radioligands were therapeutically more effective than their 177Lu-labeled counterparts, as agreed with the approximately 40% increased tumor dose of 161Tb compared with that of 177Lu. Under the given experimental conditions, no obvious adverse events were observed. Conclusion: The data of this study indicate the promising potential of 161Tb in combination with SibuDAB for RLT of prostate cancer. Future clinical studies using 161Tb-based RLT will shed light on a potential clinical benefit of 161Tb over 177Lu.
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