Tritium distribution analysis of Be limiter tiles from JET-ITER like wall campaigns using imaging plate technique and β-ray induced X-ray spectrometry

Tritium (T) distribution on the plasma-facing surfaces (PFSs) and inside castellation of Be limiter tiles from the JET tokamak with the ITER-like wall (ILW) was analyzed using imaging plate (IP) technique and β-ray induced X-ray spectrometry (BIXS). Regarding to PFSs, the outer poloidal limiter (OPL) showed significantly higher T concentrations than the inner wall guard limiter (IWGL) and upper dump plate (DP). The concentration of T on OPL was high at the central part. However, deuterium (D) and metallic impurities showed maximum concentration at the edges. This difference in distributions indicated different deposition and retention mechanisms between T and D. In contrast, deposition profiles of T concentrations on the castellated surfaces extended up to ∼ 5 mm into the gap, i.e. were similar to those of D and metallic impurities found by ion beam analysis.Peer reviewe

Evaluation of Organo [18F]Fluorosilicon Tetrazine as a Prosthetic Group for the Synthesis of PET Radiotracers

Fluorine-18 is the most widely used positron emission tomography (PET) radionuclide currently in clinical application, due to its optimal nuclear properties. The synthesis of 18F-labeled radiotracers often requires harsh reaction conditions, limiting the use of sensitive bio- and macromolecules as precursors for direct radiolabeling with fluorine-18. We aimed to develop a milder and efficient in vitro and in vivo labeling method for trans-cyclooctene (TCO) functionalized proteins, through the bioorthogonal inverse-electron demand Diels-Alder (IEDDA) reaction with fluorine-18 radiolabeled tetrazine ([18F]SiFA-Tz). Here, we used TCO-modified bovine serum albumin (BSA) as the model protein, and isotopic exchange (IE) (19F/18F) chemistry as the labeling strategy. The radiolabeling of albumin-TCO with [18F]SiFA-Tz ([18F]6), providing [18F]fluoroalbumin ([18F]10) in high radiochemical yield (99.1 ± 0.2%, n = 3) and a molar activity (MA) of 1.1 GBq/µmol, confirmed the applicability of [18F]6 as a quick in vitro fluorination reagent for the TCO functionalized proteins. While the biological evaluation of [18F]6 demonstrated defluorination in vivo, limiting the utility for pretargeted applications, the in vivo stability of the radiotracer was dramatically improved when [18F]6 was used for the radiolabeling of albumin-TCO ([18F]10) in vitro, prior to administration. Due to the detected defluorination in vivo, structural optimization of the prosthetic group for improved stability is needed before further biological studies and application of pretargeted PET imaging

Evaluation of Organo [18F]Fluorosilicon Tetrazine as a Prosthetic Group for the Synthesis of PET Radiotracers

Fluorine-18 is the most widely used positron emission tomography (PET) radionuclide currently in clinical application, due to its optimal nuclear properties. The synthesis of 18F-labeled radiotracers often requires harsh reaction conditions, limiting the use of sensitive bio- and macromolecules as precursors for direct radiolabeling with fluorine-18. We aimed to develop a milder and efficient in vitro and in vivo labeling method for trans-cyclooctene (TCO) functionalized proteins, through the bioorthogonal inverse-electron demand Diels-Alder (IEDDA) reaction with fluorine-18 radiolabeled tetrazine ([18F]SiFA-Tz). Here, we used TCO-modified bovine serum albumin (BSA) as the model protein, and isotopic exchange (IE) (19F/18F) chemistry as the labeling strategy. The radiolabeling of albumin-TCO with [18F]SiFA-Tz ([18F]6), providing [18F]fluoroalbumin ([18F]10) in high radiochemical yield (99.1 ± 0.2%, n = 3) and a molar activity (MA) of 1.1 GBq/µmol, confirmed the applicability of [18F]6 as a quick in vitro fluorination reagent for the TCO functionalized proteins. While the biological evaluation of [18F]6 demonstrated defluorination in vivo, limiting the utility for pretargeted applications, the in vivo stability of the radiotracer was dramatically improved when [18F]6 was used for the radiolabeling of albumin-TCO ([18F]10) in vitro, prior to administration. Due to the detected defluorination in vivo, structural optimization of the prosthetic group for improved stability is needed before further biological studies and application of pretargeted PET imaging

Translating the concept of peptide labeling with 5-deoxy-5-[F-18] fluororibose into preclinical practice : F-18-labeling of Siglec-9 peptide for PET imaging of inflammation

Peer reviewe

Study of interpad-gap of HPK 3.1 production LGADs with Transient Current Technique

The Phase-2 upgrade of the Large Hadron Collider (LHC) to High-Luminosity LHC (HL-LHC) allows an increase in the operational luminosity value by a factor of 5-7 that will result in delivering 3000 fb(-1) or more integrated luminosity. Due to high luminosity, the number of interactions per bunch crossings (pileup) will increase up to a value of 140-200. To cope with high pileup rates, a precision minimum ionising particles (MIPs) timing detector (MTD) with a time resolution of similar to 30-40 ps and hermetic coverage up to a pseudo-rapidity of vertical bar eta vertical bar = 3 is proposed by the Compact Muon Solenoid (CMS) experiment. An endcap part (1.6 <vertical bar eta vertical bar <3) of the MTD, called the endcap timing layer, will be based on low-gain avalanche detector (LGAD) technology. LGADs provide a good timing resolution due to a combination of a fast signal rise time and high signal-to-noise ratio. The performance of the ETL depends on optimising the crucial features of the sensors, namely; gain, signal homogeneity, fill factor, leakage current, uniformity of multiple-pad sensors and long term stability. The paper mainly focuses on the study of the fill factor of LGADs with varying temperature and irradiation at varying proton fluences as these sensors will be operated at low temperatures and are subjected to a high radiation environment. The 3.1 production of LGADs from Hamamatsu Photonics K.K. (HPK) includes 2x2 sensors with different structures, in particular, different values of narrower inactive region widths between the pads, called the no-gain region. In this paper, the term interpad-gap is used instead of no-gain region in order to follow the conventional terminology. These sensors have been designed to study their fill factor, which is the ratio of the area within the active region (gain region) to the total sensor area. A comparative study on the dependence of breakdown voltage with the interpad-gap width for the sensors has been carried out. Using infrared light (as the electron-hole pair creation by IR laser mimics closely to the traversing of MIPs) from the Scanning-Transient Current Technique (Scanning-TCT) set-up shows that the fill factor does not vary significantly with a variation in temperature and irradiation at high proton fluences.Peer reviewe

Evaluation of organo [18F]fluorosilicon tetrazine as a prosthetic group for the synthesis of PET radiotracers

Fluorine-18 is the most widely used positron emission tomography (PET) radionuclide currently in clinical application, due to its optimal nuclear properties. The synthesis of 18F-labeled radiotracers often requires harsh reaction conditions, limiting the use of sensitive bio- and macromolecules as precursors for direct radiolabeling with fluorine-18. We aimed to develop a milder and efficient in vitro and in vivo labeling method for trans-cyclooctene (TCO) functionalized proteins, through the bioorthogonal inverse-electron demand Diels-Alder (IEDDA) reaction with fluorine-18 radiolabeled tetrazine ([18F]SiFA-Tz). Here, we used TCO-modified bovine serum albumin (BSA) as the model protein, and isotopic exchange (IE) (19F/18F) chemistry as the labeling strategy. The radiolabeling of albumin-TCO with [18F]SiFA-Tz ([18F]6), providing [18F]fluoroalbumin ([18F]10) in high radiochemical yield (99.1 ± 0.2%, n = 3) and a molar activity (MA) of 1.1 GBq/µmol, confirmed the applicability of [18F]6 as a quick in vitro fluorination reagent for the TCO functionalized proteins. While the biological evaluation of [18F]6 demonstrated defluorination in vivo, limiting the utility for pretargeted applications, the in vivo stability of the radiotracer was dramatically improved when [18F]6 was used for the radiolabeling of albumin-TCO ([18F]10) in vitro, prior to administration. Due to the detected defluorination in vivo, structural optimization of the prosthetic group for improved stability is needed before further biological studies and application of pretargeted PET imaging.</p

Porous Silicon as a Platform for Radiation Theranostics Together with a Novel RIB-Based Radiolanthanoid

Mesoporous silicon (PSi) is biocompatible and tailorable material with high potential in drug delivery applications. Here, we report of an evaluation of PSi as a carrier platform for theranostics by delivering a radioactive ion beam- (RIB-) based radioactive lanthanoid into tumors in a mouse model of prostate carcinoma. Thermally hydrocarbonized porous silicon (THCPSi) wafers were implanted with Dy-159 at the facility for radioactive ion beams ISOLDE located at CERN, and the resulting [Dy-159]THCPSi was postprocessed into particles. The particles were intratumorally injected into mice bearing prostate cancer xenografts. The stability of the particles was studied in vivo, followed by ex vivo biodistribution and autoradiographic studies. We showed that the process of producing radionuclide-implanted PSi particles is feasible and that the [Dy-159]THCPSi particles stay stable and local inside the tumor over seven days. Upon release of Dy-159 from the particles, the main site of accumulation is in the skeleton, which is in agreement with previous studies on the biodistribution of dysprosium. We conclude that THCPSi particles are a suitable platform together with RIB-based radiolanthanoids for theranostic purposes as they are retained after administration inside the tumor and the radiolanthanoid remains embedded in the THCPSi.Peer reviewe

Development of [18F]AmBF3 Tetrazine for Radiolabeling of Peptides : Preclinical Evaluation and PET Imaging of [18F]AmBF3-PEG7-Tyr3-Octreotide in an AR42J Pancreatic Carcinoma Model

Radiolabeled peptides have emerged as highly specific agents for targeting receptors expressed in tumors for therapeutic and diagnostic purposes. Peptides developed for positron emission tomography (PET) are typically radiolabeled using prosthetic groups or bifunctional chelators for fast "kit-like" incorporation of the radionuclide into the structure. A novel [18F]alkylammoniomethyltrifluoroborate ([18F]AmBF3) tetrazine (Tz), [18F]AmBF3-Tz, was developed for the [18F]fluorination of trans-cyclooctene (TCO)-modified biomolecules using Tyr3-octreotides (TOCs) as model peptides. [18F]AmBF3-Tz (Am = 15.4 +/- 9.2 GBq/µmol, n = 14) was evaluated in healthy mice by ex vivo biodistribution and PET/computed tomography (CT), where the radiolabel in the prosthetic group was found stable in vivo, indicated by the low bone uptake in tibia (0.4 +/- 0.1% ID/g, t = 270 min). TCO-TOCs tailored with polyethylene glycol (PEG) linkers were radiolabeled with [18F]AmBF3-Tz, forming two new tracers, [18F]AmBF3-PEG4-TOC (Am = 2.8 +/- 1.8 GBq/µmol, n = 3) and [18F]AmBF3-PEG7-TOC (Am of 6.0 +/- 3.4 GBq/µmol, n = 13), which were evaluated by cell uptake studies and ex vivo biodistribution in subcutaneous AR42J rat pancreatic carcinoma tumor-bearing nude mice. The tracer demonstrating superior behavior ex vivo, the [18F]AmBF3-PEG7-TOC, was further evaluated with PET/CT, where the tracer provided dear tumor visualization (SUVbaseline = 1.01 +/- 0.07, vs SUVblocked = 0.76 +/- 0.04) at 25 min post injection. The novel AmBF3-Tz demonstrated that it offers potential as a prosthetic group for rapid radiolabeling of biomolecules in mild conditions using bioorthogonal chemistry.Peer reviewe

Comparison of water phase diffusion experiments in laboratory and in situ conditions

In some countries the spent nuclear fuel produced by nuclear power plants will be deposited in crystalline granitic rock formations. In Finland, a repository for the spent nuclear fuel is being built at Olkiluoto. The safety assessment of the repository requires a careful determination of the transport properties of the bedrock. The porosity of the bedrock and the effective diffusion coefficients and distribution coefficients of different radio-nuclides for the bedrock are used as the main parameters in the safety assessment calculations. It has been questioned whether the parameters determined using laboratory experiments can be used to estimate the parameters in the in situ conditions. In this study, laboratory and in situ water phase diffusion experiments (WPDEs) were performed to resolve the issue. In the experiments, the transport of tritiated water (HTO), Cl-36, and Na-22 was studied using similar experimental setups. Mathematical models were constructed and solved to determine the transport parameters from the measured breakthrough curves. On average, the in situ WPDEs resulted in 20 (+/- 6)% smaller porosities and 32 (+/- 10)% smaller effective diffusion coefficients for HTO and Cl-36 than the laboratory WPDEs. It was also found that in veined gneiss, the most dominant rock type of the Olkiluoto bedrock, anion exclusion reduced the retention parameters of Cl-36 compared with those of HTO. Furthermore, the distribution coefficient of Na-22 for veined gneiss was about one order of magnitude smaller in the in situ conditions than in previous laboratory batch sorption experiments. The effects of the results on the safety assessment were evaluated and discussed.Peer reviewe