1,720,996 research outputs found
Pharmaceutical development of the ISOL technique for the production of radionuclides and their applications in targeted radionuclide therapy
Get PDFRadiopharmaceuticals are the fundamental tool for nuclear medicine procedures, enabling imaging and therapy of cancer after administration of a radioligand. Imaging or therapy are performed with radionuclides that are bound to a ligand, which selectively accumulates into cancer tissues. The discovery of new radionuclides on one side and the optimization of ligands on the other are fundamental parts of the research in the radiopharmaceutical field.
In the first part of this thesis work we aimed at the development of a new technique for the production of pure radionuclides. The study was born from the collaboration between the Department of Pharmaceutical and Pharmacological Sciences (DSF) of the University of Padua (UniPD) and the Legnaro National Laboratories (LNL) of the National Institute for Nuclear Physics (INFN), where the Selective Production of Exotic Species (SPES) project is under development. This project aims at the production of Radioactive Ion Beams (RIBs) by means of the Isotope Separation On-Line technique (ISOL), which can be exploited for radionuclides production. Thanks to mass separation, a feature of the ISOL technique, radionuclides can be produced at high purity because isotopic contaminants can be cleared away easily. Suitable secondary targets (chapter 2) were developed to allow ion beams collection, depending on the accelerated ions. To verify the suitability of the method for radionuclides production, tests with accelerated stable ion beams were carried out and are described in chapter 3. The SPES test bench was used for the elements ionization and acceleration. The beams were collected on the produced secondary targets and quantified. The tests were carried out for yttrium, iodine and copper, elements interesting for the production of 90Y, 125/127/131I and 64/67Cu. The ISOL method guarantees the purification of the radionuclides from the isotopic contaminants, but isobaric and pseudo-isobaric contaminants can be present in the beam and thus in the final solution. For this reason chemical purification methods have to be developed for radionuclides purification. In chapter 4 the synthesis of an inorganic material (sodium nonatitanate) and its use for strontium and yttrium purification is described.
The second part of this thesis, chapters 5 and 6, was developed in collaboration with the group of PD Dr. Cristina Müller at the Center for Radiopharmaceutical Sciences (CRS) of Paul Scherrer Institute (PSI).
Targeted radionuclide therapy (TRT) represents one of the most promising therapeutic strategies for cancer therapy ; it is based on the use of energetic particles (alpha, beta- or Auger electrons) selectively delivered in proximity of tumors thanks to specific biologic features. Small molecules are an attractive strategy for active targeted delivery because they are amenable for chemical synthesis and have some advantages if compared with high molecular weight vehicles, such as antibodies.
A potential challenge of small molecular radiotherapeutics is their fast elimination from the body preventing sufficient accumulation of radioactivity in the malignancies due to glomerular filtration and fast renal clearance; high accumulation of radioactivity in the kidneys increases at the same time the risk of nephrotoxicity. For this reason, new strategies to allow a higher translation from preclinical to clinical phase of small molecule-based radiopharmaceuticals should be developed.
In this thesis project two strategies to improve TRT with small molecules were developed. The first relies on the development of radioligands with a serum protein-binding domain. This strategy is based on the consideration that serum proteins have high molecular weight, and for this reason do not undergo glomerular filtration (filtration cut-off 30-50 kDa). In particular, three serum proteins-binding compounds were radiolabeled and characterized in vitro and in vivo (chapter 5).
Another strategy to improve TRT efficacy while decreasing side effects is the use of combined-modality regimens. This approach is very popular in cancer therapy since targeting the cancer cell on diverse molecular path mechanisms makes the cell less prone to developing resistance to the therapy. At the same time, the use of multimodality therapies allows to decrease the dosage of single therapies, thus reducing side-effects. In the last chapter of this thesis (chapter 6) a preliminary study combining radionuclide therapy (177Lu-cm10) with two tyrosine kinases inhibitors is described, based on the assumptions of a possible synergistic effect of the two agents
Sintesi e purificazione dei precursori di desossiCBD per formulazioni innovative per cannabinoidi
No full textResearch and technological development of beta-emitting radiopharmaceuticals produced with radioactive ion beams
No full textAn innovative method is proposed for the production of carrier-free - radiopharmaceuticals, based on the Isotope Separation On-Line (ISOL) technique in the framework of the SPES (Selective Production of the Exotic Species) project. SPES is a nuclear physics project under advanced construction at Legnaro National Laboratories of INFN (Istituto Nazionale di Fisica Nucleare).
The innovation of the method relies not only on the new physical technique but mainly on the final product. The class of radiopharmaceutical obtainable, indeed, can be considered completely new, since they have a high purity in terms of specific activity (5 orders of magnitude bigger than traditional ones); specific activity is the ratio between radioactivity and mass of the element
Synthesis and purification of desoxy-CBD precursors for innovative pain therapy formulations
No full text
Sviluppi del progetto Isolpharm: deposizione e recupero di Iodio da un facio di ioni accelerati con tecnologia Isol per radiofarmaci innovativi
No full textL’APPROCCIO TENSIOMETRICO NEL CAMPO DELLA TECNOLOGIA FARMACEUTICA: ESPERIENZE, APPLICAZIONI E PROSPETTIVE
No full textGoing Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Get PDF“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Get PDFWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
- …
