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Folate receptor targeted alpha-therapy using terbium-149.

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.
AuthorsCristina Müller, Josefine Reber, Stephanie Haller, Holger Dorrer, Ulli Köster, Karl Johnston, Konstantin Zhernosekov, Andreas Türler, Roger Schibli
JournalPharmaceuticals (Basel, Switzerland) (Pharmaceuticals (Basel)) Vol. 7 Issue 3 Pg. 353-65 (Mar 13 2014) ISSN: 1424-8247 [Print] Switzerland
PMID24633429 (Publication Type: Journal Article)

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