title: 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.
authors.affiliation: Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Paul Scherrer Institute, 5232 Villigen-PSI, Switzerland. cristina.mueller@psi.ch.
authors.forename: Cristina
authors.initials: C
authors.lastname: Müller
authors.affiliation: Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Paul Scherrer Institute, 5232 Villigen-PSI, Switzerland. josefine.reber@gmail.com.
authors.forename: Josefine
authors.initials: J
authors.lastname: Reber
authors.affiliation: Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Paul Scherrer Institute, 5232 Villigen-PSI, Switzerland. stephanie.haller@psi.ch.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Haller
authors.affiliation: Laboratory of Radiochemistry and Environmental Chemistry, Paul Scherrer Institute, 5232 Villigen-PSI, Switzerland. holger.dorrer@psi.ch.
authors.forename: Holger
authors.initials: H
authors.lastname: Dorrer
authors.affiliation: Institut Laue-Langevin, 38000 Grenoble, France. koester@ill.fr.
authors.forename: Ulli
authors.initials: U
authors.lastname: Köster
authors.affiliation: Physics Department, ISOLDE/CERN, 1211 Geneva, Switzerland. karl.johnston@cern.ch.
authors.forename: Karl
authors.initials: K
authors.lastname: Johnston
authors.affiliation: Laboratory of Radiochemistry and Environmental Chemistry, Paul Scherrer Institute, 5232 Villigen-PSI, Switzerland. konstantin.zhernosekov@gmail.com.
authors.forename: Konstantin
authors.initials: K
authors.lastname: Zhernosekov
authors.affiliation: Laboratory of Radiochemistry and Environmental Chemistry, Paul Scherrer Institute, 5232 Villigen-PSI, Switzerland. andreas.tuerler@psi.ch.
authors.forename: Andreas
authors.initials: A
authors.lastname: Türler
authors.affiliation: Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Paul Scherrer Institute, 5232 Villigen-PSI, Switzerland. roger.schibli@psi.ch.
authors.forename: Roger
authors.initials: R
authors.lastname: Schibli