PET imaging using titanium-45: Could it be useful?

In the last decade a wider application of positron emission tomography (PET) as one of the most powerful medical imaging technologies was observed. This was largely due to the increased availability of equipment dedicated to production of radioisotopes, mainly due to the installation of low energy cyclotrons in hospitals, research institutes and pharmaceutical industries specialized in radiopharmaceutical production.info:eu-repo/semantics/publishedVersio

Cyclotron Production of Unconventional Radionuclides for PET Imaging: the Example of Titanium-45 and Its Applications

Positron emitting radionuclides are used to label different compounds, allowing the study of the major biological systems using PET (positron emission tomography) imaging. Although there are several radionuclides suited for PET imaging, routine clinical applications are still based on a restrict group constituted by 18F, 11C, and, more recently, 68Ga. However, with the enlarged availability of low-energy cyclotrons and technical improvements in radionuclide production, the use of unconventional radionuclides is progressively more common. Several examples of unconventional radionuclides for PET imaging are being suggested, and 45Ti could be suggested as a model, due to its interesting properties such as its abundant positron emission (85%), reduced positron energy (β+ endpoint energy = 1040 keV), physical half-life of 3.09 h, and interesting chemical properties. This review aims to introduce the role of cyclotrons in the production of unconventional radionuclides for PET imaging while using 45Ti as an example to explore the potential biomedical applications of those radionuclides in PET imaginginfo:eu-repo/semantics/publishedVersio

The use of radiolabeled nanoparticles for biomedical imaging

Introduction: In the last years, the practice of medicine is being changing with a special emphasis on the application of technological innovations where medical imaging modalities play an important role. Between several imaging modalities, Molecular Imaging (that is essentially based on Nuclear Medicine) is one of the most interesting solutions. On the other hand, assuming that nanoparticles are being studied as drug delivery systems, its application as vectors for radionuclide-based imaging is in a clear growing

Effect of low level contamination on TiAl alloys studied by SIMS

Titanium aluminides are a valuable alternative to superalloys in applications where the ratio resistance/density is important. Since the ordinary production routes lead to high final costs, an alternative might be the use of traditional casting techniques by induction melting of the alloy in a ceramic crucible and pouring into ceramic moulds, made by the investment casting process. However, due to the high reactivity of Ti alloys, traditional ceramic materials cannot be used, as they lead to oxide formation and oxygen pick up from both the crucible and the moulding materials. In this work, the effect of low level contaminations was studied by SIMS. Special attention was given to the oxygen concentration of samples obtained with different mould materials. The comparison of SIMS in-depth profiles with hardness profiles, give insight concerning the significance of the oxygen concentration in the properties of the alloy and regarding the choice of the most suitable materials for TiAl production

Espectroscopia gama: desenvolvimento de um software automático de análise e simulação

A espectroscopia gama é uma metodologia útil em contextos de identificação, caracterização e quantificação de radiação ionizante. Entre outras, permite a monitorização da radiação ambiental, a detecção e quantificação de impurezas radioactivas ou mesmo o estudo aprofundado de materiais. Deste modo, importa conhecer de forma precisa os espectros característicos dos isótopos radioactivos de interesse. Este trabalho visa apresentar o processo de desenvolvimento de um software, criado com recurso à plataforma MATLAB, capaz de gerar espectros gama completos e/ou de os analisar de forma automática. Até à data, concentraram-se esforços para fontes de 22Na e 60Co e detectores cintiladores de NaI(Tl)

Application of Monte Carlo simulation codes to plan an activation experiment in Scandium-45 targets

Data characterizing excitation functions of nuclear reactions are necessary for different applications, with the process of radionuclide production being assumed as a relevant example. This is the only way to define and optimize technical parameters involved in such a process. However, nuclear activation experimental studies are sometimes difficult to implement, and care should be taken before its execution, in order to obtain all relevant data, while correctly planning the experiences. In this context, Monte Carlo simulation tools are widely applied to overtake such difficulties. This work describes a case-study aiming to characterize nuclear reactions excitation functions induced by a proton beam and its interaction with a Scandium target – a specific situation that is not yet completely characterized and that might be of relevance, since it could be useful to produce medically relevant radionuclides (eg. Titanium-45)

45Ti - Titanium: from cyclotron production to potential applications evaluation

Introduction: Thousands of radioisotopes are known and virtually all may be artificially produced, however clinical applications of PET imaging are mainly based on 18F, 11C, 13N and 68Ga. This trend could change in the near future, since several groups worldwide are busy developing very promising new entities aiming to contribute for spreading the use and efficacy of clinical diagnostic using Nuclear Medicine imaging techniques. Our group is developing 45Ti-Titanium, assuming it as a potential candidate, since presenting interesting properties: physical half-life of 3.09h, together with relevant chemical properties, that enable radiolabelling with bifunctional chelates, ligands or could even be useful for studies concerning the distribution of new titanium-based chemotherapy drugs or titanium oxide nanoparticles. Considering that data characterizing excitation functions is necessary for radionuclide optimal production, this work aims to disseminate results regarding the determination of excitation function of 45Sc(p,n)45Ti reaction, studied as a potential route to produce 45Ti in low energy cyclotrons

Neuronal cell-based high-throughput screen for enhancers of mitochondrial function reveals luteolin as a modulator of mitochondria-endoplasmic reticulum coupling

Background: Mitochondrial dysfunction is a common feature of aging, neurodegeneration, and metabolic diseases. Hence, mitotherapeutics may be valuable disease modifiers for a large number of conditions. In this study, we have set up a large-scale screening platform for mitochondrial-based modulators with promising therapeutic potential. Results: Using differentiated human neuroblastoma cells, we screened 1200 FDA-approved compounds and identified 61 molecules that significantly increased cellular ATP without any cytotoxic effect. Following dose response curve-dependent selection, we identified the flavonoid luteolin as a primary hit. Further validation in neuronal models indicated that luteolin increased mitochondrial respiration in primary neurons, despite not affecting mitochondrial mass, structure, or mitochondria-derived reactive oxygen species. However, we found that luteolin increased contacts between mitochondria and endoplasmic reticulum (ER), contributing to increased mitochondrial calcium (Ca2+) and Ca2+-dependent pyruvate dehydrogenase activity. This signaling pathway likely contributed to the observed effect of luteolin on enhanced mitochondrial complexes I and II activities. Importantly, we observed that increased mitochondrial functions were dependent on the activity of ER Ca2+-releasing channels inositol 1,4,5-trisphosphate receptors (IP3Rs) both in neurons and in isolated synaptosomes. Additionally, luteolin treatment improved mitochondrial and locomotory activities in primary neurons and Caenorhabditis elegans expressing an expanded polyglutamine tract of the huntingtin protein. Conclusion: We provide a new screening platform for drug discovery validated in vitro and ex vivo. In addition, we describe a novel mechanism through which luteolin modulates mitochondrial activity in neuronal models with potential therapeutic validity for treatment of a variety of human diseases

Limited effect of chronic valproic acid treatment in a mouse model of Machado-Joseph disease

Machado-Joseph disease (MJD) is an inherited neurodegenerative disease, caused by a CAG repeat expansion within the coding region of ATXN3 gene, and which currently lacks effective treatment. In this work we tested the therapeutic efficacy of chronic treatment with valproic acid (VPA) (200mg/kg), a compound with known neuroprotection activity, and previously shown to be effective in cell, fly and nematode models of MJD. We show that chronic VPA treatment in the CMVMJD135 mouse model had limited effects in the motor deficits of these mice, seen mostly at late stages in the motor swimming, beam walk, rotarod and spontaneous locomotor activity tests, and did not modify the ATXN3 inclusion load and astrogliosis in affected brain regions. However, VPA chronic treatment was able to increase GRP78 protein levels at 30 weeks of age, one of its known neuroprotective effects, confirming target engagement. In spite of limited results, the use of another dosage of VPA or of VPA in a combined therapy with molecules targeting other pathways, cannot be excluded as potential strategies for MJD therapeuticsPM received funding from Ataxia UK Grant (Project: Pharmacologic therapy for Machado-Joseph disease: from a C. elegans drug screen to a mouse model validation). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.info:eu-repo/semantics/publishedVersio