BEGIN:VCALENDAR VERSION:2.0 PRODID:-//CERN//INDICO//EN BEGIN:VEVENT SUMMARY:Immunological Changes During Space Travel: A Ground-Based Evaluati on of the Impact of Neutron Dose Rate on Plasma Cytokine Levels in Human W hole Blood Cultures DTSTART;VALUE=DATE-TIME:20231130T125500Z DTEND;VALUE=DATE-TIME:20231130T131000Z DTSTAMP;VALUE=DATE-TIME:20260606T133345Z UID:indico-contribution-572-3396@indico.tlabs.ac.za DESCRIPTION:Speakers: Randall Fisher (Division of Radiation Biophysics\, N RF iThemba LABS)\nConsidering the upcoming long-duration spaceflight missi ons\, a better understanding of the impact of spaceflight exposome on huma n health is urgently warranted. Consequently\, particle accelerator facili ties implement ground-based\, Radiobiology experiments investigating the h ealth effects of simulated-space environments with simulated-psychological or physical stressors. iThemba LABS is such a facility\, with a proton va ult enabling Spaceflight Radiobiology. Historically\, the immune system is notably highly sensitive to spaceflight stressors although\, there’s li mited information on the impact of the complex space radiation environment on the astronauts' immune functioning. This pilot study presents a first step in implementation of ground-based setups with neutron irradiation\, w hich is an important intra-spacecraft radiation component. \nWhole-blood s amples (n=8) were exposed to 0.125 or 1Gy of neutron irradiation (fluence- weighted average energy 29.8MeV) at a lower 0.015Gy/min (LDR) or higher 0. 400Gy/min dose rate (HDR). Post-irradiation\, blood samples were stimulate d with lipopolysaccharide (LPS)\, heat-killed Listeria monocytogenes (HKLM ) or pokeweed mitogen (PWM)\, before 24hrs incubation. Cell-mediated immun ity was examined using the Cytokine Release Assay to analyse interleukin-2 (IL-2)\, interferon-gamma (IFN-γ)\, tumour necrosis factor-alpha (TNF-α ) and interleukin-10 (IL-10) plasma levels. \nStimulants significantly inc reased all cytokine levels except IL-2\, where only PWM induced significan t increases. Generally\, no statistically-significant changes were observe d in IL-2\, IFN γ\, and TNF α concentrations\, irrespective of dose or d ose rate\, when compared to stimulated\, sham-irradiated controls. After P WM-stimulation\, IL-10 levels were significantly increased at 0.125Gy HDR and 1Gy LDR. Pooled analysis showed that HDR significantly increased IL-2 titres (under PWM-stimulation) and IFN-γ titres (with all stimulants)\, b ut significantly decreased TNF-α secretion\, without stimulation. \nLimit ed sample numbers restricted strong conclusions in this pilot study invest igating the effect of neutron radiation as a single-stressor on cytokine s ecretion\, induced by various stimulants. An interesting dose rate effects was observed\, which encourages future investigations into the synergisti c effects of multiple spaceflight stressors on immune functioning.\n\nhttp s://indico.tlabs.ac.za/event/119/contributions/3396/ LOCATION: URL:https://indico.tlabs.ac.za/event/119/contributions/3396/ END:VEVENT BEGIN:VEVENT SUMMARY:123I-ADAM10 inhibitor as a new theranostic agent for cervical canc er DTSTART;VALUE=DATE-TIME:20231130T124000Z DTEND;VALUE=DATE-TIME:20231130T125500Z DTSTAMP;VALUE=DATE-TIME:20260606T133345Z UID:indico-contribution-572-3393@indico.tlabs.ac.za DESCRIPTION:Speakers: Julie Bolcaen (Radiobiology\, Radiation Biophysics\, iThemba LABS\, Cape Town)\nThe aim of this study is to evaluate the suita bility of ADAM10 as a target for imaging cervical cancer using a 123I-radi olabelled ADAM10 inhibitor. A Disintegrin and Metalloproteinases (ADAMs) e xhibit proteolytic activity like matrix metalloproteinases and ADAM10 shed s a range of membrane-bound proteins that play a role in cancer progressio n\, radioresistance and the tumor micro-environment. First\, the therapeut ic and radiosensitizing effects of the non-radiolabelled ADAM10 inhibitor (GI254023X\, GI) were evaluated in cervical cancer cells (Hela\, C33A). Th is includes effects on proliferation\, clonogenicity\, migration\, invasio n\, apoptosis\, DNA damage and adhesion. Preliminary results show an inhib ition of migration but no effect on cell cycle progression\, apoptosis\, n or radiosensitizing effects. Secondly\, GI was radiolabelled with Iodine-1 23 (98% radiochemical purity\, ± 44 MBq/mL). 123I-GI is enantiomerically pure with a thermal stability up to 125°C. Whole blood and protein bindin g studies confirmed a 34% binding to read blood cells with 66% activity lo cated in serum (0-1-2-24 hrs). Within the serum\, 33% was protein bound. T he partition coefficient indicated a lipophilicity of 0.555. Preliminary i n vitro studies demonstrated that 123I-GI was taken up in cervical cancer cells. Blocking studies with an overdose of cold GI did not affect the upt ake of 123I-GI in Hela/C33A cells. The effect of 123I-GI on clonogenicity of Hela/C33A cells is ongoing (auger effect). The potential of 123I-GI as a cancer diagnostic agent will further be investigated using a xenograft c ervical cancer model. The biodistribution\, pharmacokinetics and targeting will be determined in vivo (µSPECT-CT and autoradiography). All these in vitro\, ex vivo and in vivo validations of GI and 123I-GI will give more insights into the cell surface protein’s activity\, function and its rol e in tumorigenesis. This will set the scene for evaluating GI linked to th e alpha therapeutic nuclide 211At or the beta emitting 131I. This study wi ll be the first step in establishing a pipeline for theranostics research at iThemba LABS.\n\nhttps://indico.tlabs.ac.za/event/119/contributions/339 3/ LOCATION: URL:https://indico.tlabs.ac.za/event/119/contributions/3393/ END:VEVENT BEGIN:VEVENT SUMMARY:Determination of the response function of the LaBr3(Ce) detector f or g-quanta\, formed during inelastic scattering of neutrons with an energ y of 14.1 MeV on oxigen nuclei DTSTART;VALUE=DATE-TIME:20231130T122500Z DTEND;VALUE=DATE-TIME:20231130T124000Z DTSTAMP;VALUE=DATE-TIME:20260606T133345Z UID:indico-contribution-572-3397@indico.tlabs.ac.za DESCRIPTION:Speakers: Dimitar Grozdanov ()\nThe work is devoted to determi ning the response function of the detector LaBr3(Ce) for γ -quanta\, form ed during inelastic scattering of neutrons with energy of 14.1 MeV on the nuclei 16O. In gamma spectrometry\, output pulses are recorded\, the ampli tudes of which are proportional to the energy lost in the detection medium by incident photons. One of the main tasks of radiation detection is to r estore radiation characteristics from signals measured at the outputs of d etectors. For this\, it is necessary to know\, first of all\, the general characteristics of detectors as converters of radiation into signals. The main characteristic of the detector is its response function\, which can b e defined as the probability that a particle with given properties generat es a certain signal in the detector that will be registered by the device. The article presents the results of modeling the response function of a s cintillation detector based on a LaBr3(Ce) crystal for gamma radiation fro m inelastic fast neutron scattering in order to study the mechanism of its formation.\nThis work was supported by the RSCF grant 23-12-00239.\n\nhtt ps://indico.tlabs.ac.za/event/119/contributions/3397/ LOCATION: URL:https://indico.tlabs.ac.za/event/119/contributions/3397/ END:VEVENT BEGIN:VEVENT SUMMARY:Cyclotron-Production of Innovative Radionuclides: Direct Activatio n and ISOL Technique Experience at INFN-LNL DTSTART;VALUE=DATE-TIME:20231130T120000Z DTEND;VALUE=DATE-TIME:20231130T122500Z DTSTAMP;VALUE=DATE-TIME:20260606T133345Z UID:indico-contribution-572-3335@indico.tlabs.ac.za DESCRIPTION:Speakers: Michele Ballan (INFN-LNL)\nIntroduction\nThe cyclotr on-based production of radionuclides for medicine is one of the research a ctivities carried out in the framework of the SPES (Selective Production o f Exotic Species) project at the Legnaro National Laboratories of the Nati onal Institute for Nuclear Physics (INFN-LNL). The heart of SPES is the 70 MeV proton-cyclotron with a dual-beam extraction\, installed in 2015 in a new building equipped with ancillary laboratories currently under complet ion.\n\nDescription of the Work or Project\nThe SPES project aims at the c onstruction of an advanced ISOL (Isotope Separation On-Line) facility for the production of re-accelerated exotic ion beams for nuclear physics stud ies. The double-beam extraction of the cyclotron also allows to perform mu ltidisciplinary activities\, such as radionuclides production for medical applications and neutron-based research. This work will mainly present the activities carried out in the unit “Radionuclides for medicine and appl ied physics”\, showing the major results obtained with the interdiscipli nary projects LARAMED (LAboratory of RAdionuclides for MEDicine) [Esposito et al.] and ISOLPHARM [Andrighetto et al.]. LARAMED is based on the direc t-activation method\, and it includes the proton-based production of 99mTc \, 67Cu\, 52/51Mn\, 47Sc and recently Tb-isotopes\, from the nuclear cross section measurements to the preclinical studies. ISOLPHARM uses the ISOL technique for the development and the production of radioisotopes with hig h-specific activity\, such as 111Ag\, going beyond the state-of-art in the field. \n\nConclusions\nThanks to a consolidated network of collaboration s with national and international facilities\, including the PRISMAP Europ ean consortium and several Italian universities and hospitals\, the ongoin g research activities on radionuclides production and their perspectives a t the INFN-LNL will be presented at the African Nuclear Physics Conference (ANPC2023). \n\nReferences\n\nJ. Esposito et al. (2019)\, LARAMED: a LAbo ratory for Radioisotopes of MEDical interest\, Molecules 24(1)\, 20\, http s://doi.org/10.3390/molecules24010020\nA. Andrighetto et al.\, ISOLPHARM w ebsite\, https://isolpharm.pd.infn.it/web/\n\nhttps://indico.tlabs.ac.za/e vent/119/contributions/3335/ LOCATION: URL:https://indico.tlabs.ac.za/event/119/contributions/3335/ END:VEVENT END:VCALENDAR