Pharmaceuticals 2014, 7(3), 353-365; doi:10.3390/ph7030353
Article

Folate Receptor Targeted Alpha-Therapy Using Terbium-149

1,* email, 1email, 1email, 2,3email, 4email, 5email, 2email, 2,3email and 1,6email
Received: 18 November 2013; in revised form: 21 February 2014 / Accepted: 6 March 2014 / Published: 13 March 2014
(This article belongs to the Special Issue Radiopharmaceutical Chemistry between Imaging and Radioendotherapy)
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract: Terbium-149 is among the most interesting therapeutic nuclides for medical applications. It decays by emission of short-range α-particles (Eα = 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.
Keywords: terbium-149; alpha-therapy; folate receptor; DOTA-folate; KB tumors; 149Tb-cm09; albumin binder, radionuclide therapy
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MDPI and ACS Style

Müller, C.; Reber, J.; Haller, S.; Dorrer, H.; Köster, U.; Johnston, K.; Zhernosekov, K.; Türler, A.; Schibli, R. Folate Receptor Targeted Alpha-Therapy Using Terbium-149. Pharmaceuticals 2014, 7, 353-365.

AMA Style

Müller C, Reber J, Haller S, Dorrer H, Köster U, Johnston K, Zhernosekov K, Türler A, Schibli R. Folate Receptor Targeted Alpha-Therapy Using Terbium-149. Pharmaceuticals. 2014; 7(3):353-365.

Chicago/Turabian Style

Müller, Cristina; Reber, Josefine; Haller, Stephanie; Dorrer, Holger; Köster, Ulli; Johnston, Karl; Zhernosekov, Konstantin; Türler, Andreas; Schibli, Roger. 2014. "Folate Receptor Targeted Alpha-Therapy Using Terbium-149." Pharmaceuticals 7, no. 3: 353-365.

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