Cyclotron Produced Radionuclides: Emerging Positron Emitters for Medical Applications: 64Cu and 124I

1.1.BACKGROUNDThe application of radionuclides in medicine has undergone significant growth in the last two decades, with the availability of a large number of cyclotrons exclusively dedicated to their production contributing to this growth, The widespread use of positron emission tomography (PET) in oncology and the rapid dissemination of PET--computed tomography (PET -CT) cameras throughout the world have revolutionized nuclear medicine. The rapidly growing fleet of modern cameras and the progress in molecular imaging signify that clinical PET will grow beyond present state of the art 2-[18F] fluoro-2-deoxy-D-glucose(18F-FDG) imaging in diagnosis and staging in oncology, New 18F tracers will certainly drive some of this expansion, but there is a growing understanding that many physiological and biological uptake mechanisms in humans are slow when compared to the short half-life of 18F. An abundant positron emission and long half-life are in general not favoured for nuclear physics reasons, however a handful of such isotopes have been explored and reported on by researchers in the past. Among these, only two at present deserve to be raised to the level of being called \u27emerging PET isotopes\u27: 64Cu and 124I. A third isotope, 89Zr, might deserve to be added to this category, and could prove to be ideally suited for future use in PET labelled antibodies. New radiopharmaceuticals which can be routinely used for diagnosis or for evaluation of cancer therapy would be valuable additions to the arsenal available to the nuclear medicine physician. There is great potential forproduction and development of new radiopharmaceuticals using PET radionuclides other than 18F and 11C at most of the present day medical cyclotron facilities with cyclotrons in the energy range of 10-20 MeV. Cyclotron time is usually available for research, but there are several other factors to be addressed in the development and use of new radiopharmaceuticals. More than 30 potentially useful cyclotron produced positron emitting radionuclides havebeen reported, and 64CU and 1241 in particular have received considerable attention. Because of low positron energy, low abundance of gamma radiation, suitable half-life and favourable coordination chemistry, these radionuclidesare attracting widespread interest. There are two major challenges in wider production of these PET tracers:(1) The targets for the production of these radionuclides are not widely available or are considered too difficult to use.(2) The separation of the radionuclide from the target material requires ion exchange chromatography or thermal diffusion and the labelling efficiency of the resultant nuclide needs to be further developed.There is a need to evaluate and compare the emerging radionuclides as imaging agents. The most widespread medical applications of these non-standard PET radionuclides are in oncology for labelling of proteins, particularlyimmunoglobulins (antibodies to tumour specific antigens), and of small peptides which recognize receptors expressed on tumours. Some examples of applications would be:(a) As diagnostic PET imaging agents (with greater biological specificity than 18F_FDG). Such a diagnostic tracer, for example, would differentiate between malignant tumours and benign conditions such as sarcoidosis.This currently is a problem when using 18F-FDG, which mimics increased anaerobic glucose metabolism in tumours but also inflammatory processes.(b) To identifY patients with specific tumour phenotypes for novel targeted therapies (e.g. antibody therapies).(c) To provide improved dosimetry of therapeutic radionuclides based upon improved quantitation of tumour and normal tissue (organ) distribution using PET instrumentation. In particular, the use of PET radionuclides with a longer half-life than 18F, such as 1241 or 64Cu, provides information required for optimal organ and tumour dosimetry.Even though interest in the use of these radionuclides for clinical application is steadily increasing, support from the (radio)pharmaceutical industry is rather limited. The major reason is that large scale production for provision of a sufficient number of customers is technically not achievable, whereas local, small scale production, on the other hand, is economically not very attractive. In this respect, the IAEA\u27s role in fostering streamlined research and production· capacities in Member States is of great importance to further develop this field and in general for these health care applications where short lived radionuclides are being used

Crp79p, Like Mex67p, Is an Auxiliary mRNA Export Factor in Schizosaccharomyces pombe

The export of mRNA from the nucleus to the cytoplasm involves interactions of proteins with mRNA and the nuclear pore complex. We isolated Crp79p, a novel mRNA export factor from the same synthetic lethal screen that led to the identification of spMex67p in Schizosaccharomyces pombe. Crp79p is a 710-amino-acid-long protein that contains three RNA recognition motif domains in tandem and a distinct C-terminus. Fused to green fluorescent protein (GFP), Crp79p localizes to the cytoplasm. Like Mex67p, Crp79-GFP binds poly(A)(+) RNA in vivo, shuttles between the nucleus and the cytoplasm, and contains a nuclear export activity at the C-terminus that is Crm1p-independent. All of these properties are essential for Crp79p to promote mRNA export. Crp79p import into the nucleus depends on the Ran system. A domain of spMex67p previously identified as having a nuclear export activity can functionally substitute for the nuclear export activity at the C-terminus of Crp79p. Although both Crp79p and spMex67p function to export mRNA, Crp79p does not substitute for all of spMex67p functions and probably is not a functional homologue of spMex67p. We propose that Crp79p is a nonessential mRNA export carrier in S. pombe

Olive Oil as a Functional Food: Nutritional and Health Benefits

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