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

Folate Receptor Targeted Alpha-Therapy Using Terbium-149

1,* , 1
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1 Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Paul Scherrer Institute, 5232 Villigen-PSI, Switzerland 2 Laboratory of Radiochemistry and Environmental Chemistry, Paul Scherrer Institute, 5232 Villigen-PSI, Switzerland 3 Laboratory of Radiochemistry and Environmental Chemistry, Department of Chemistry and Biochemistry University of Bern, 3012 Berne, Switzerland 4 Institut Laue-Langevin, 38000 Grenoble, France 5 Physics Department, ISOLDE/CERN, 1211 Geneva, Switzerland 6 Department of Chemistry and Applied Biosciences, ETH Zurich, 8093 Zurich, Switzerland
* Author to whom correspondence should be addressed.
Received: 18 November 2013 / Revised: 21 February 2014 / Accepted: 6 March 2014 / Published: 13 March 2014
(This article belongs to the Special Issue Radiopharmaceutical Chemistry between Imaging and Radioendotherapy)
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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 terbium-149; alpha-therapy; folate receptor; DOTA-folate; KB tumors; 149Tb-cm09; albumin binder, radionuclide therapy
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).
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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.

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