[en] The purpose of the present research was to provide a radiation-chemical basis for the use of tertiary-butyl acrylate gels in radio-fluorogenic dose-imaging applications (Warman et al. 2011a,b, 2013a,b). The radiation-induced polymerization of tertiary-butyl acrylate (TBA) results in the formation of a transparent gel with an optical density lower than 0.1 cm⁻¹ from 600 nm down to 315 nm. The fractional monomer-to-polymer conversion, C_M, determined gravimetrically, increases super-linearly with dose, D Gy. Up to C_M≈40%, and over the dose rate range D′=3.5 to 49 cGy s⁻¹, the dose dependence is given by C_M=[1+AC_M]KD/√D′ with K=1.43×10⁻³ Gy^−0.5 s^−0.5 and A=0.70. For D′=3.5 cGy s⁻¹ the average polymer size is estimated to be 1.2×10⁵ monomer units or 17 megadalton. For C_M≥10% the gel is quasi-rigid, displaying little tendency to flow on a timescale of an hour or more. After removal of monomer by evacuation, the gel can be reformed by adding a volume of monomer to the remaining polymer equal to that removed and allowing this to swell for several days. The dose and dose rate dependence of radiation-induced monomer conversion in the reformed gel show no evidence of a discontinuity caused by the intervening evacuation and reformation procedures. - Highlights: • Gamma-ray polymerization of tertiary-butyl acrylate; dose and dose-rate dependences of monomer conversion. • The radiolytic production of a rigid, UV/vis transparent organic gel. • Primary radiolytic processes relevant to the preparation and application of a radio-fluorogenic polymer-gel. • Reformation of an organic polymer gel by swelling subsequent to removal of monomer by evacuation

[en] We prepared ¹⁶⁶Dy labelled gold nanoparticles via a seed-mediated growth method. First, ¹⁶⁶Dy was co-reduced with a gold precursor to form a Dy-Au nanoparticle seed. Then an extra gold layer was grown on top of the seed nanoparticles to form a core-shell structured nanoparticle, i.e. DyAu@Au nanoparticle. The final product had a diameter of 5 nm and a ¹⁶⁶Dy labelling efficiency of 60 %. The ¹⁶⁶Ho retention tests showed that more than 95 % of ¹⁶⁶Ho was retained for at least 72 hours at 37℃ in water. To the best of our knowledge, this is the first study to retain radionuclides freed due to internal conversion with gold nanoparticles. Overall, this study presents a simple, quick, and chelator-free radiolabelling method for ¹⁶⁶Dy with minimum loss of internally converted ¹⁶⁶Ho.

No abstract available

[en] In Conway and Pleydell-Pearce's model (2000), autobiographical memories are viewed as transitory mental representations, more often generated in an effort-full way. An important claim of the model concerns the dynamic process that evolves over time, from the left prefrontal areas to posterior regions, to retrieve specific memories. The present work aims at investigating, using fMRI, the temporal distribution of effort-full autobiographical memory construction. In addition, a self-paced design was implemented to elucidate the question of the timing window required to evoke recollections. The results showed a large pattern of brain regions, which included the two major poles of activation predicted by Conway and Pleydell-Pearce's model. Likewise, we were able to detect the earlier implication of the left dorso-lateral prefrontal cortex, by comparison with posterior structures, which seemed to confirm its involvement in the effort-full retrieval process. Finally, the self-paced procedure allowed us to refine the timing window necessary to construct past events. (authors)

No abstract available

[en] To minimize the systemic toxicity of chemotherapeutics, we designed a prodrug (also called caged drug), which becomes active only upon removal of a protecting group, triggered by external ionizing radiation. Using such a strategy, the drug toxicity to healthy tissue is greatly reduce, while still achieving high killing efficiency to tumour cells. To proof this concept, a fluorescent probe, 4-methyl-7-hydroxycoumarin, was used as the reporter instead of the drug, to enable easy evaluation of the working mechanism. The hydroxy group of the probe was protected by an aryl boronate ester based self-immolative linker through a carbonate bond, and thus the fluorescence is largely quenched because of the electron withdrawing property of the latter. The aryl boronate ester can be oxidised by hydrogen peroxide which is generated by the radiolysis of water, leading to the release of the reporter (the fluorescent probe). When this compound was irradiated by X-ray or gamma radiation, a significant increase of the emission intensity was observed, which demonstrates that the protecting group was successfully removed. More importantly, an increase of fluorescence emission intensity is already detected when the probe solution is exposed to just 2 Gy of radiation, which is typically used in external beam therapy. After confirming the release of the reporter triggered by ionizing radiation, we replace the fluorescent probe by a widely used anti-tumour drug, doxorubicin. The toxicity of this prodrug appeared to be 10 times less than free drug, and the release of doxorubicin after irradiation was successfully detected by liquid chromatography-mass spectrometry (LC-MS). Currently we are conducting cell experiments to test the killing efficiency of this prodrug when exposed to ionizing radiation and determine its potential in combined chemo- and radiotherapy.

[en] Malignant mesothelioma is a highly aggressive neoplasm of pleura with a very poor overall survival. The peak incidence was reached in year 2000, however today its decreasing tendency is attributed to cessation of asbestos exposure being a major risk factor of this disease. Latest research shows the incidence of MPM (Malignant Pleural Mesothelioma) is driven by the germ line mutation of BAP1 gene (BRCA associated protein 1) as well as development of somatic mutations. Multimodal therapy is currently the most efficient treatment method of malignant mesothelioma, and as such it provides concurrent local and systemic control of the disease. The latest effective drug to be approved for the 1st line treatment was the introduction of pemetrexed in combination with cisplatin. The results of the MAPS (Mesothelioma Avastin Cisplatin Pemetrexed )study have shown significant of OS (overall survival) improvement when bevacizumab was added to the combination of cisplatin with pemetrexed. Despite modest increase in OS, adding bevacizumab to this combination did not become a routine practice in most countries of the world, yet it is recommended as a treatment of choice by NCCN (National Comprehensive Cancer Network). Many clinical studies are currently under way for the treatment of MPM. Promising modalities include the modulation of check point inhibitor targets such as anti-CTLA4, anti-PD-1/anti-PD-L1, mesothelin as well as arginine deprivation therapy. (author)

[en] Chromium-51 (⁵¹Cr) is an attractive radionuclide in the clinical application for labelling of red blood cells, diagnosis of gastrointestinal bleeding and assessing life span of red cells. This work reports that synthesis of two chromium-based metal-organic frameworks (MOFs) as radiation targets to produce high specific activity ⁵¹Cr production utilizing the Szilard-Chalmers effect. First, the radiation stability of two MOFs under high gamma doses was determined. The results showed that MIL-100 (Cr) and MIL-101 (Cr) exhibited excellent radiation stability after exposure to gamma radiation dose of 4 MGy. However, MIL-101 (Cr) started decomposing with increasing gamma dose, while MIL-100 (Cr) still kept a stable crystal structure at even higher radiation dose. Subsequently the Cr-MOFs were irradiated in the HOR reactor of the Reactor Institute Delft. The ⁵¹Cr yield and specific activity was determined at different irradiation time, extracting agents, extraction time and temperature. The best results show that high enrichment factor (>500) and yield (>40%) can be achieved, appearing a promising ⁵¹Cr production routes for nuclear medicine.

[en] While alpha microdosimetry dates back a couple of decades, the effects of localized energy deposition of alpha particles are often still unclear since few comparative studies have been performed. Most modern alpha microdosimetry studies rely for large parts on simulations, which negatively impacts both the simplicity of the calculations and the reliability of the results. A novel microdosimetry method based on the Fluorescent Nuclear Track Detector, a versatile tool that can measure individual alpha particles at sub-micron resolution, yielding accurate energy, fluence and dose rate measurements, was introduced to address these issues. Both the detectors and U87 glioblastoma cell cultures were irradiated using an external Am241 alpha source. The alpha particle tracks measured with a Fluorescent Nuclear Track Detector were used together with high resolution 3D cell geometries images to calculate the nucleus dose distribution in the U87 glioblastoma cells. The experimentally obtained microdosimetry parameters were thereafter applied to simulations of 3D U87 cells cultures (spheroids) with various spatial distributions of isotopes to evaluate the effect of the nucleus dose distribution on the expected cell survival. The new experimental method showed good agreement with the analytically derived nucleus dose distributions. Small differences (< 5%) in the relative effectiveness were found for isotopes in the cytoplasm and on the cell membrane versus external irradiation, while isotopes located in the nucleus or on the nuclear membrane showed a substantial increase in relative effectiveness (33 – 51%). The ease-of-use, good accuracy and use of experimentally derived characteristics of the radiation field make this method superior to conventional simulation-based microdosimetry studies. Considering the uncertainties found in alpha radionuclide carriers in-vivo and in-vitro, together with the large contributions from the relative biological effectiveness and the oxygen enhancement ratio, it is expected that only carriers penetrating or surrounding the cell nucleus will substantially benefit from microdosimetry.

[en] We have proposed the idea of a ^177mLu/¹⁷⁷Lu radionuclide generator for ¹⁷⁷Lu production based on the separation of the daughter nuclei, ¹⁷⁷Lu from its parent nuclei, ^177mLu. In our work, ^177mLu-DOTA-(Tyr3)-octreotate (DOTATATE) complex was retained on tC-18 silica and the bond ruptured ¹⁷⁷Lu ions was collected using a mobile phase flow. Using this method of separation, ¹⁷⁷Lu/ ^177mLu activity ratios were increased from 0.25 (in equilibrium) to values around 250. The ¹⁷⁷Lu was collected with efficiencies of about 65%. However in order to meet the clinical demands ¹⁷⁷Lu/^177mLu activity ratios close to 10,000 is needed. In our current research we are exploiting the potential of solvent extraction in separating the two isomers. ^177mLu is complexed with different chelating agents such as 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), DOTA-(Tyr3)-octreotate (DOTATATE) and others. The aqueous solution of complexed ^177mLu is left at a fixed temperature for a fixed interval of time to allow the accumulation of ¹⁷⁷Lu. After the fixed accumulation period, it is stirred with an immiscible organic phase (dihexyl ether) containing an extracting agent, Di-(2-ethylhexyl)phosphoric acid (DEHPA) serves to collect the free ¹⁷⁷Lu. Using this method of separation we are able to achieve ¹⁷⁷Lu/^177mLu activity ratios close to 3000, with a ¹⁷⁷Lu collection efficiency close to 50%. By optimizing the extraction process and by utilizing a microfluidic device we aim to deliver a system able to reach the quality needed for medical applications and to provide with a generator with ease of use that can provide with ¹⁷⁷Lu for long periods of time on location.