Considerable progress has been made in various fields of applied research on the use of carbon nanotubes (CNTs). Because CNTs are fibrous nanomaterials, biosafety of CNTs has been discussed. The biokinetic data of CNTs, such as using the radioisotope of carbon and surface labeling of CNTs, have been reported. However, the use of radioisotopes requires a special facility. In addition, there are problems in the surface labeling of CNTs, including changes in surface properties and labels eliminating over time. In order to solve these problems and properly evaluate the biokinetics of CNTs, the authors synthesize peapods with platinum (Pt) encapsulated within the hollow region of Double-Walled CNTs (DWCNTs) and develop a new system to evaluate biokinetics using widely available imaging equipment. In the cell assay, no significant difference is observed with and without Pt in CNTs. In animal studies, radiography of the lungs of rats that inhaled Pt-peapods show the detectability of Pt inside the CNTs. This new method using Pt-peapods enables image evaluation with a standard radiographic imaging device without changing the surface property of the CNTs and is effective for biokinetics evaluation of CNTs.

Single-walled carbon nanotubes (SWNTs) can deliver imaging agents or drugs to tumours and offer significant advantages over approaches based on antibodies or other nanomaterials. In particular, the nanotubes can carry a substantial amount of cargo (100 times more than a monoclonal antibody), but can still be rapidly eliminated from the circulation by renal filtration, like a small molecule, due to their high aspect ratio. Here we show that SWNTs can target tumours in a two-step approach in which nanotubes modified with morpholino oligonucleotide sequences bind to cancer cells that have been pretargeted with antibodies modified with oligonucleotide strands complementary to those on the nanotubes. The nanotubes can carry fluorophores or radioisotopes, and are shown to selectively bind to cancer cells in vitro and in tumour-bearing xenografted mice. The binding process is also found to lead to antigen capping and internalization of the antibody-nanotube complexes. The nanotube conjugates were labelled with both alpha-particle and gamma-ray emitting isotopes, at high specific activities. Conjugates labelled with alpha-particle-generating (225)Ac were found to clear rapidly, thus mitigating radioisotope toxicity, and were shown to be therapeutically effective in vivo.

The marine cyanobacterium Prochlorococcus can utilize glucose as a source of carbon. However, the relative importance of inorganic and organic carbon assimilation and the timing of glucose assimilation are still poorly understood in these numerically dominant cyanobacteria. Here, we investigated whole microbial community and group-specific primary production and glucose assimilation using incubations with radioisotopes combined with flow cytometry cell sorting. We also studied changes in the microbial community structure in response to glucose enrichments and analyzed the transcription of Prochlorocccus genes involved in carbon metabolism and photosynthesis. Our results showed a diel variation for glucose assimilation in Prochlorococcus, with maximum assimilation at midday and minimum at midnight (~2-fold change), which was different from that of the total microbial community. This suggests that the timing in glucose assimilation in Prochlorococcus is coupled to photosynthetic light reactions producing energy, it being more convenient for Prochlorococcus to show maximum glucose uptake precisely when the rest of microbial populations have their minimum glucose uptake. Many transcriptional responses to glucose enrichment occurred after 12- and 24-h periods, but community composition did not change. High-light Prochlorococcus strains were the most impacted by glucose addition, with transcript-level increases observed for genes in pathways for glucose metabolism, such as the pentose phosphate pathway, the Entner-Doudoroff pathway, glycolysis, respiration, and glucose transport. While Prochlorococcus C assimilation from glucose represented less than 0.1% of the bacterium's photosynthetic C fixation, increased assimilation during the day and glcH gene upregulation upon glucose enrichment indicate an important role of mixotrophic C assimilation by natural populations of Prochlorococcus. IMPORTANCE Several studies have demonstrated that Prochlorococcus, the most abundant photosynthetic organism on Earth, can assimilate organic molecules, such as amino acids, amino sugars, ATP, phosphonates, and dimethylsulfoniopropionate. This autotroph can also assimilate small amounts of glucose, supporting the hypothesis that Prochlorococcus is mixotrophic. Our results show, for the first time, a diel variability in glucose assimilation by natural populations of Prochlorococcus with maximum assimilation during midday. Based on our previous results, this indicates that Prochlorococcus could maximize glucose uptake by using ATP made during the light reactions of photosynthesis. Furthermore, Prochlorococcus showed a different timing of glucose assimilation from the total population, which may offer considerable fitness advantages over competitors "temporal niches." Finally, we observed transcriptional changes in some of the genes involved in carbon metabolism, suggesting that Prochlorococcus can use both pathways previously proposed in cyanobacteria to metabolize glucose.

Quantitative and qualitative characterization of fluorinated molecules represents an important task. Fluorine-based medicinal chemistry is a fast-growing research area due to the positive impact of fluorine in drug discovery, and clinical and molecular imaging (e.g., magnetic resonance imaging, positron emission tomography). Common detection methods include fluorinated-based labelling using radioactive isotopes or fluorescent dyes. Nevertheless, these molecular imaging methods can be harmful for health due to the potential instability of fluorochromes and cytoxicity of radioisotopes. Therefore, these methods often require expensive precautionary measures. In this context, we have developed, validated and patented carbon-fluorine spectroscopy (CFS™), recently renamed Spectro-Fluor™ technology, which among a non-competitive family of in-house made devices called PLIRFA™ (Pulsed Laser Isochronic Raman and Fluorescence Apparatus™), allows reliable detection of Carbon-Fluorine (C-F) bonds. C-F bonds are known to be stable and safe labels once incorporated to any type of molecules, cells, compounds or (nano-) materials. In this pioneered research study, we used Spectro-Fluor™ to assess biomarkers. As a proof-of-principle experiment, we have established a three-step protocol intended to rapid protein detection, which simply consisted of: (i) incorporating a sufficient concentration of an aromatic amino-acid (fluorinated versus non-fluorinated) into cultured cells; (ii) simultaneously isolating the fluorinated protein of interest and the non-fluorinated form of the protein (control) by immune-precipitation; (iii) comparatively analyzing the respective spectrum obtained for the two protein forms by Spectro-Fluor™. Thereby, we were able to differentiate, from colon cancer cells HCT-116, the fluorinated and non-fluorinated forms of p21, a key transcriptional factor and downstream target of p53, the so-called "guardian of the genome". Taken together, our data again demonstrates the beneficial alternative use of Spectro-Fluor™, which once combined with an innovative methodology permits one to quickly, reliably, safely and cost-effectively detect physiological or pathological proteins in cells.

The development of a reliable dose monitoring system in hadron therapy is essential in order to control the treatment plan delivery. Positron Emission Tomography (PET) is the only method used in clinics nowadays for quality assurance. However, the accuracy of this method is limited by the loss of signal due to the biological washout processes. Up to the moment, very few studies measured the washout processes and there is no database of washout data as a function of the tissue and radioisotope. One of the main difficulties is related to the complexity of such measurements, along with the limited time slots available in hadron therapy facilities. Thus, in this work, we proposed an alternative in vivo methodology for the measurement and modeling of the biological washout parameters without any radiative devices. It consists in the implementation of a point-like radioisotope source by direct injection on the tissues of interest and its measurement by means of high-resolution preclinical PET systems. In particular, the washout of 11C carbonate radioisotopes was assessed, considering that 11C is is the most abundant β+ emitter produced by carbon beams. 11C washout measurements were performed in several tissues of interest (brain, muscle and 9L tumor xenograf) in rodents (Wistar rat). Results show that the methodology presented is sensitive to the washout variations depending on the selected tissue. Finally, a first qualitative correlation between 11C tumor washout properties and tumor metabolism (via 18F-FDG tracer uptake) was found.