Folate Receptor Targeted Alpha-Therapy Using Terbium-149

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.

Comparative Cytotoxicity Study of Silver Nanoparticles (AgNPs) in a Variety of Rainbow Trout Cell Lines (RTL-W1, RTH-149, RTG-2) and Primary Hepatocytes.

Among all classes of nanomaterials, silver nanoparticles (AgNPs) have potentially an important ecotoxicological impact, especially in freshwater environments. Fish are particularly susceptible to the toxic effects of silver ions and, with knowledge gaps regarding the contribution of dissolution and unique particle effects to AgNP toxicity, they represent a group of vulnerable organisms. Using cell lines (RTL-W1, RTH-149, RTG-2) and primary hepatocytes of rainbow trout (Oncorhynchus mykiss) as in vitro test systems, we assessed the cytotoxicity of the representative AgNP, NM-300K, and AgNO3 as an Ag+ ion source. Lack of AgNP interference with the cytotoxicity assays (AlamarBlue, CFDA-AM, NRU assay) and their simultaneous application point to the compatibility and usefulness of such a battery of assays. The RTH-149 and RTL-W1 liver cell lines exhibited similar sensitivity as primary hepatocytes towards AgNP toxicity. Leibovitz's L-15 culture medium composition (high amino acid content) had an important influence on the behaviour and toxicity of AgNPs towards the RTL-W1 cell line. The obtained results demonstrate that, with careful consideration, such an in vitro approach can provide valuable toxicological data to be used in an integrated testing strategy for NM-300K risk assessment.

Tooth loss, chewing efficiency and cognitive impairment in geriatric patients.

BACKGROUND Patients with dementia have poorer oral health and fewer teeth than their peers without cognitive impairment. OBJECTIVE The hypothesis of this study is that the number of natural teeth and the chewing efficiency are associated with cognitive functioning. METHODS This cross-sectional study included 29 patients diagnosed with dementia aged 75 years or older and 22 controls who were either cognitively normal (n = 19) or with mild cognitive impairment (n = 3). Neuropsychological, nutritional and dental assessments were performed. The chewing efficiency was evaluated with a two-colour mixing test. RESULTS Demented patients and controls presented with a mean of 4.9 and 6.5 teeth, respectively (n.s.). The number of natural teeth was not associated with dementia (p = 0.553). Same results were found for age (p = 0.746) and sex (p = 0.901). The chewing efficiency by visual inspection proved worse in participants with dementia than in the controls (p < 0.011) and explained 9.3% of the variance in the diagnosis of dementia. Neither dental state nor chewing efficiency was related to the nutritional state. CONCLUSION Chewing efficiency seems stronger associated with cognitive impairment than the number of teeth. Hence, in a more holistic approach for the geriatric assessment, the dental examination may be complemented by a chewing efficiency test.