Siwowska Klaudia, Guzik Patrycja, Domnanich Katharina A, Monné Rodríguez Josep M, Bernhardt Peter, Ponsard Bernard, Hasler Roger, Borgna Francesca, Schibli Roger, Köster Ulli, van der Meulen Nicholas P, Müller Cristina
Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Paul Scherrer Institute, 5232 Villigen-PSI, Switzerland.
Laboratory of Radiochemistry, Paul Scherrer Institute, 5232 Villigen-PSI, Switzerland.
Pharmaceutics. 2019 Aug 20;11(8):424. doi: 10.3390/pharmaceutics11080424.
Targeted radionuclide therapy with Lu- and Y-labeled radioconjugates is a clinically-established treatment modality for metastasized cancer. Sc is a therapeutic radionuclide that decays with a half-life of 3.35 days and emits medium-energy β-particles. In this study, Sc was investigated, in combination with a DOTA-folate conjugate, and compared to the therapeutic properties of Lu-folate and Y-folate, respectively. In vitro, Sc-folate demonstrated effective reduction of folate receptor-positive ovarian tumor cell viability similar to Lu-folate, but Y-folate was more potent at equal activities due to the higher energy of emitted β-particles. Comparable tumor growth inhibition was observed in mice that obtained the same estimated absorbed tumor dose (~21 Gy) when treated with Sc-folate (12.5 MBq), Lu-folate (10 MBq), and Y-folate (5 MBq), respectively. The treatment resulted in increased median survival of 39, 43, and 41 days, respectively, as compared to 26 days in untreated controls. There were no statistically significant differences among the therapeutic effects observed in treated groups. Histological assessment revealed no severe side effects two weeks after application of the radiofolates, even at double the activity used for therapy. Based on the decay properties and our results, Sc is likely to be comparable to Lu when employed for targeted radionuclide therapy. It may, therefore, have potential for clinical translation and be of particular interest in tandem with Sc or Sc as a diagnostic match, enabling the realization of radiotheragnostics in future.
用镥和钇标记的放射性缀合物进行靶向放射性核素治疗是一种已确立的转移性癌症临床治疗方式。钪是一种治疗性放射性核素，半衰期为3.35天，发射中能β粒子。在本研究中，研究了钪与一种DOTA - 叶酸缀合物的组合，并分别与镥 - 叶酸和钇 - 叶酸的治疗特性进行了比较。在体外，钪 - 叶酸显示出与镥 - 叶酸相似的有效降低叶酸受体阳性卵巢肿瘤细胞活力的效果，但由于发射的β粒子能量较高，在相同活度下钇 - 叶酸更有效。在用钪 - 叶酸（12.5 MBq）、镥 - 叶酸（10 MBq）和钇 - 叶酸（5 MBq）治疗的小鼠中，当给予相同估计的肿瘤吸收剂量（约21 Gy）时，观察到了类似的肿瘤生长抑制。与未治疗的对照组的26天相比，该治疗分别使中位生存期延长至39天、43天和41天。在治疗组中观察到的治疗效果之间没有统计学上显著差异。组织学评估显示，在应用放射性叶酸两周后，即使在治疗所用活度加倍的情况下，也没有严重的副作用。基于衰变特性和我们的结果，钪在用于靶向放射性核素治疗时可能与镥相当。因此，它可能具有临床转化的潜力，并且与钪或钪作为诊断匹配物联用可能特别有意义，有望在未来实现放射治疗诊断一体化。
