Development of a dosimetric model for in vitro labelled cells with ß + emitters in PET tracking studies.

Positron emission tomography (PET) offers an effective method for tracking ß + emitters-labeled cells in vivo. However, in vitro high labelling activities used may cause cell damage or death. Our understanding of the impact of such procedure remains limited by the fact that the biological effects are usually linked to the activity per cell rather than the absorbed dose. To assess the dose delivered to the cells during the radiolabelling, a multi-cellular dosimetry computational tool was developed, allowing the study of two key parameters: the cell density and the labelling efficiency. Through a hybrid method based on Monte Carlo simulations (MCNP6 code) and an analytical approach implemented in Python, the mean absorbed dose received by a target cell was calculated for distributions with a very large number of cells-up to hundreds of millions. An advanced investigation of in vitro cell labelling with ß-emitting radionuclides was carried out via (i) a systematic study of the effects of the labelling parameters on the cell absorbed dose for 18F, 64Cu and 68Ga, and (ii) a quantitative comparison between cellular and conventional dosimetry. The results provided a thorough analysis of how the dose (self, cross and extracellular medium dose contributions) varies with the initial labelling parameters selected and highlighted the conditions where the cellular dosimetry is required over the conventional dosimetry. The dosimetric model was finally applied to real conditions of 18F-FDG labelling on the basis of eight reported studies. The results showed that similar activity per cell can lead to significantly different absorbed dose and pointed out differences between cellular and conventional dosimetry up to a factor of 5.

Sol-gel derived lithium-releasing glass for cartilage regeneration.

Wnt-signalling cascade is one of the crucial pathways involved in the development and homeostasis of cartilage. Influencing this pathway can potentially contribute to improved cartilage repair or regeneration. One key molecular regulator of the Wnt pathway is the glycogen synthase kinase-3 enzyme, the inhibition of which allows initiation of the signalling pathway. This study aims to utilise a binary SiO2-Li2O sol-gel derived glass for controlled delivery of lithium, a known glycogen synthase kinase-3 antagonist. The effect of the dissolution products of the glass on chondrogenic differentiation in an in vitro 3D pellet culture model is reported. Dissolution products that contained 5 mM lithium and 3.5 mM silicon were capable of inducing chondrogenic differentiation and hyaline cartilaginous matrix formation without the presence of growth factors such as TGF-ß3. The results suggest that sol-gel derived glass has the potential to be used as a delivery vehicle for therapeutic lithium ions in cartilage regeneration applications.

Lithium-silicate sol-gel bioactive glass and the effect of lithium precursor on structure-property relationships.

ABSTRACT: This work reports the synthesis of lithium-silicate glass, containing 10 mol% of Li 2 O by the sol-gel process, intended for the regeneration of cartilage. Lithium citrate and lithium nitrate were selected as lithium precursors. The effects of the lithium precursor on the sol-gel process, and the resulting glass structure, morphology, dissolution behaviour, chondrocyte viability and proliferation, were investigated. When lithium citrate was used, mesoporous glass containing lithium as a network modifier was obtained, whereas the use of lithium nitrate produced relatively dense glass-ceramic with the presence of lithium metasilicate, as shown by X-ray diffraction, 29 Si and 7 Li MAS NMR and nitrogen sorption data. Nitrate has a better affinity for lithium than citrate, leading to heterogeneous crystallisation from the mesopores, where lithium salts precipitated during drying. Citrate decomposed at a lower temperature, where the crystallisation of lithium-silicate crystal is not thermodynamically favourable. Upon decomposition of the citrate, a solid-state salt metathesis reaction between citrate and silanol occurred, followed by the diffusion of lithium within the structure of the glass. Both glass and glass-ceramic released silica and lithium ions in culture media, but release rate was lower for the glass-ceramic. Both samples did not affect chondrocyte viability and proliferation.