Folate Receptor Targeted Alpha-Therapy Using Terbium-149

Pharmaceuticals

Cristina Müller²  Josefine Reber²  Stephanie Haller²  Holger Dorrer³  Ulli Köster⁴  Karl Johnston¹  Konstantin Zhernosekov³  Andreas Türler³ 

[1] Physics Department, ISOLDE/CERN, 1211 Geneva, Switzerland; E-Mail:;Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Paul Scherrer Institute, 5232 Villigen-PSI, Switzerland; E-Mails:;Laboratory of Radiochemistry and Environmental Chemistry, Paul Scherrer Institute, 5232 Villigen-PSI, Switzerland; E-Mails:;Institut Laue-Langevin, 38000 Grenoble, France; E-Mail:

关键词: terbium-149;    alpha-therapy;    folate receptor;    DOTA-folate;    KB tumors;    ¹⁴⁹Tb-cm09;    albumin binder;    radionuclide therapy;   

DOI  :  10.3390/ph7030353

来源: mdpi

【 摘 要 】

Terbium-149 is among the most interesting therapeutic nuclides for medical applications. It decays by emission of short-range α-particles (E_α = 3.967 MeV) with a half-life of 4.12 h. The goal of this study was to investigate the anticancer efficacy of a ¹⁴⁹Tb-labeled DOTA-folate conjugate (cm09) using folate receptor (FR)-positive cancer cells in vitro and in tumor-bearing mice. ¹⁴⁹Tb was produced at the ISOLDE facility at CERN. Radiolabeling of cm09 with purified ¹⁴⁹Tb resulted in a specific activity of ~1.2 MBq/nmol. In vitro assays performed with ¹⁴⁹Tb-cm09 revealed a reduced KB cell viability in a FR-specific and activity concentration-dependent manner. Tumor-bearing mice were injected with saline only (group A) or with ¹⁴⁹Tb-cm09 (group B: 2.2 MBq; group C: 3.0 MBq). A significant tumor growth delay was found in treated animals resulting in an increased average survival time of mice which received ¹⁴⁹Tb-cm09 (B: 30.5 d; C: 43 d) compared to untreated controls (A: 21 d). Analysis of blood parameters revealed no signs of acute toxicity to the kidneys or liver in treated mice over the time of investigation. These results demonstrated the potential of folate-based α-radionuclide therapy in tumor-bearing mice.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland.