Folate Receptor Targeted Alpha-Therapy Using Terbium-149

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(3), pp. 353-365. MDPI 10.3390/ph7030353

[img]
Preview
Text
pharmaceuticals-07-00353.pdf - Published Version
Available under License Creative Commons: Attribution (CC-BY).

Download (534kB) | Preview

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.

Item Type:

Journal Article (Original Article)

Division/Institute:

08 Faculty of Science > Departement of Chemistry and Biochemistry

UniBE Contributor:

Türler, Andreas

Subjects:

500 Science > 570 Life sciences; biology
500 Science > 540 Chemistry

ISSN:

1424-8247

Publisher:

MDPI

Language:

English

Submitter:

Franziska Bornhauser-Rufer

Date Deposited:

18 Mar 2015 15:51

Last Modified:

09 May 2018 12:10

Publisher DOI:

10.3390/ph7030353

BORIS DOI:

10.7892/boris.65205

URI:

https://boris.unibe.ch/id/eprint/65205

Actions (login required)

Edit item Edit item
Provide Feedback