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.
Highlights
Targeted radionuclide therapy using β−-particle-emitting radionuclides (e.g., 131I, 90Y, 177Lu) of variable energies is employed in clinical routine
A promising option for a potential improvement of the therapeutic efficacy of radioendotherapy may be the selection of appropriate radionuclides. α-Particles of medically interesting radionuclides provide a 200to 1,000-fold higher linear energy transfer (LET) than β−-particles [3,4]
Because of the much shorter path-length (25–100 μm) of α-particles compared to β−-particles (0.05–12 mm), α-particle-emitting nuclides may be interesting for targeted radionuclide therapy of micrometastases or even single cancer cells
Summary
Targeted radionuclide therapy using β−-particle-emitting radionuclides (e.g., 131I, 90Y, 177Lu) of variable energies is employed in clinical routine. It emits γ-rays of an energy (Eγ = 165 keV, 26.4%) potentially suitable for single photon emission computed tomography (SPECT) and positrons (Eβ+ average = 638 keV, 3.8%) which may be detected via positron emission tomography (PET) (Figure 1A) [4,6]. The longer-lived in vivo generator 212Pb/212Bi (T1/2 = 10.64 h) might be a more favorable solution but could suffer from release of the 212Bi from the DOTA complex [12] In such cases the decay of the daughter nuclides may occur in non-targeted organs which could cause undesired toxicity to healthy tissue [13].
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