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Jurisson, Silvia S.

Publications and source records attributed to Jurisson, Silvia S..

At least 19 records
All sourcesNASA NTRSDOE OSTI
DOE OSTI2024

Production of High Specific Activity 72 Se/ 72 As, 117m Sn and 203 Pb for Research and Clinical Applications: Effective target design, recycling of target material and radioisotope separation

This grant involved four objectives for producing high specific activity radionuclides using reactor and accelerator technologies that would find use in medical, industrial and research applications. This grant continued a collaboration between the scientists at the University of Washington (UW), the University of Missouri (MU) and Brookhaven National Laboratory (BNL) and addresses the need for high specific activity radionuclides, both reactor- and accelerator-produced, and for the training and education of radiochemists in isotope production, separations and precursor syntheses. All three institutions were involved in the projects, but to different degrees. The chemistry graduate students (Ph.D. program at MU) may have participated in an internship at one of the other institutions for training and project translation/facilitation.

07 ISOTOPE AND RADIATION SOURCES↗
DOE OSTI2023

Production and Separations for High Specific Activity 186 Re, 189 Re and 47 Sc for Research and Clinical Applications: effective design of targets and recycling of targets and radioisotope separation

This grant involved three objectives for producing high specific activity radionuclides using reactor and accelerator technologies that would find use in medical, industrial and research applications. There was a strong emphasis in all projects to develop and train staff and students in all aspects of targetry, reactor and accelerator production, separation of radionuclides from enriched target material, and evaluating the specific activity of the product radionuclides. An additional objective was training of students (undergraduate, graduate, postdoctoral) in all aspects of radiochemistry.

07 ISOTOPE AND RADIATION SOURCES↗
DOE OSTI2022

Evaluation of 186 WS 2 target material for production of high specific activity 186 Re via proton irradiation: separation, radiolabeling and recovery/recycling

Enriched tungsten disulfide ( 186 WS 2 ) was evaluated at increasing proton beam currents (20-50 µA) and times (up to 4 h) on a GE PETtrace cyclotron for production of high specific activity (HSA) 186 Re. The HSA 186 Re was separated from the irradiated target as [ 186 Re][ReO 4 ] - by a liquid-liquid extraction method and radiolabeled with a new N 2 S 2 ligand (222-MAMA-N-ethylpropionate). The enriched 186 W was recovered from the extraction process, analyzed for purity and enrichment, and converted back to the disulfide ( 186 WS 2 ). The results demonstrate that the 186 WS 2 is an easily pressed target material that can withstand relatively high currents and can be readily recovered and recycled. The 186 Re produced was isolated in high specific activity and readily formed the radiotracers [ 186 Re][ReO(222-MAMA-N ethylpropionate)] and [ 186 Re][Re(CO) 3 (OH 2 ) 3 ] + .

186Re,N2S2 ligand↗
DOE OSTI2022

Iron Availability within the Leaf Vasculature Determines the Magnitude of Iron Deficiency Responses in Source and Sink Tissues in Arabidopsis

Abstract Iron (Fe) uptake and translocation in plants are fine-tuned by complex mechanisms that are not yet fully understood. In Arabidopsis thaliana, local regulation of Fe homeostasis at the root level has been extensively studied and is better understood than the systemic shoot-to-root regulation. While the root system is solely a sink tissue that depends on photosynthates translocated from source tissues, the shoot system is a more complex tissue, where sink and source tissues occur synchronously. In this study, and to gain better insight into the Fe deficiency responses in leaves, we overexpressed Zinc/Iron-regulated transporter-like Protein (ZIP5), an Fe/Zn transporter, in phloem-loading cells (proSUC2::AtZIP5) and determined the timing of Fe deficiency responses in sink (young leaves and roots) and source tissues (leaves). Transgenic lines overexpressing ZIP5 in companion cells displayed increased sensitivity to Fe deficiency in root growth assays. Moreover, young leaves and roots (sink tissues) displayed either delayed or dampened transcriptional responses to Fe deficiency compared to wild-type (WT) plants. We also took advantage of the Arabidopsis mutant nas4x-1 to explore Fe transcriptional responses in the opposite scenario, where Fe is retained in the vasculature but in an unavailable and precipitated form. In contrast to proSUC2::AtZIP5 plants, nas4x-1 young leaves and roots displayed a robust and constitutive Fe deficiency response, while mature leaves showed a delayed and dampened Fe deficiency response compared to WT plants. Altogether, our data provide evidence suggesting that Fe sensing within leaves can also occur locally in a leaf-specific manner.

Cell Biology↗
DOE OSTI2022

Development and biodistribution studies of 77 As-labeled trithiol RM2 bioconjugates for prostate cancer: Comparison of [ 77 As]As-trithiol-Ser-Ser-RM2 vs. [ 77 As]As-trithiol-Glu-Ser-RM2

Recent progress with the production of 72 As (2.49 Mev β + max (64%), 3.33 Mev β + max (16%), 834 keV (81%), t 1/2 : 26 h) and 77 As (0.683 Mev β- max (97%), 239 keV (1.59%), t 1/2 : 38.8 h) has facilitated their evaluation as a potential “theranostic pair” for PET imaging and radiotherapy. Our 3 rd generation trithiol chelate with two carboxylic acid groups was further developed as a bifunctional chelate for radioarsenic. The As complex with the trithiol chelate was synthesized and characterized. No carrier added (nca) [ 77 As][H 2 AsO 4 - ] was used for radiolabeling studies. Here, the trithiol chelate was conjugated to the RM2 peptide (DPhe-Gln-Trp-Ala-VaI-Gly-His-Sta-Leu-NH 2 ) via solid phase peptide synthesis with two different linkers, Ser-Ser and Glu-Ser. The trithiol chelate and its RM2 bioconjugates were radiolabeled with nca 77 As, and the RM2 bioconjugates were compared in initial biodistribution studies. The As diacid trithiol complex was characterized by 1 H NMR, 13 C NMR and HR-ESI-MS. The trithiol-RM2 precursor and As trithiol bioconjugates were characterized by HR-ESI-MS and/or LC-ESI-MS. Radiolabeling of the RM2 bioconjugates with 77 As resulted in over 85% radiochemical yield for [ 77 As]As-trithiol-Ser-Ser-RM2 ([ 77 As]8) and 90% for [ 77 As]As-trithiol-Glu-Ser-RM2 ([ 77 As]9). Both radiotracers demonstrated excellent in vitro stability (≥ 90% remaining intact through 24 h in PBS buffer) and were more hydrophilic than previous analogues based on log D 7.4 values. Biodistribution results of the two radiotracers in healthy CF-1 male mice demonstrated blockable pancreatic uptake at 1 h (82% for ([ 77 As]8 and 78% for [ 77 As]9) indicating specific gastrin-releasing peptide receptor (GRPR) uptake. The primary route of excretion was through the gastrointestinal system for both radiotracers. A new trithiol chelate with improved hydrophilicity was successfully conjugated to the RM2 peptide via two linkers, and high radiolabeling yield with nca 77 As was achieved. In vivo biodistribution studies with both radiotracers demonstrated blockable pancreatic uptake suggestive of specific receptor uptake.

07 ISOTOPE AND RADIATION SOURCES↗
DOE OSTI2021

A Third Generation Potentially Bifunctional Trithiol Chelate, Its nat,1XX Sb(III) Complex, and Selective Chelation of Radioantimony ( 119 Sb) from Its Sn Target

The therapeutic potential of the Meitner-Auger- and conversion-electron emitting radionuclide 119 Sb remains unexplored because of the difficulty of incorporating it into biologically targeted compounds. To address this challenge, we report the development of 119 Sb production from electroplated tin cyclotron targets and its complexation by a novel trithiol chelate. Here, the chelation reaction occurs in harsh solvent conditions even in the presence of large quantities of tin, which are necessary for production on small, low energy (16 MeV) cyclotrons. The 119 Sb-trithiol complex has high stability and can be purified by HPLC. The third generation trithiol chelate and the analogous stable nat Sb-trithiol compound were synthesized and characterized, including by single crystal X-ray diffraction analyses.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2019

Chelators and metal complex stability for radiopharmaceutical applications

Abstract Diagnostic and therapeutic nuclear medicine relies heavily on radiometal nuclides. The most widely used and well-known radionuclide is technetium-99m ( 99m Tc), which has dominated diagnostic nuclear medicine since the advent of the 99 Mo/ 99m Tc generator in the 1960s. Since that time, many more radiometals have been developed and incorporated into potential radiopharmaceuticals. One critical aspect of radiometal-containing radiopharmaceuticals is their stability under in vivo conditions. The chelator that is coordinated to the radiometal is a key factor in determining radiometal complex stability. The chelators that have shown the most promise and are under investigation in the development of diagnostic and therapeutic radiopharmaceuticals over the last 5 years are discussed in this review.

Chemistry↗
DOE OSTI2019

Cross-section measurements and production of 72 Se with medium to high energy protons using arsenic containing targets

Here, experiments were performed to evaluate production of 72 Se, parent radionuclide of the positron emitter 72 As, at high energy at the Brookhaven Linac Isotope Producer (BLIP). Excitation functions for 75 As(p, xn) 72/75 Se in the 52-105 MeV energy range were measured by irradiating thin gallium arsenide (GaAs) wafers. Maximum cross section value for the nat As(p, 4n) 72 Se reaction in the energy range was 103 ± 9 mb at 52 ± 1 MeV. Production size GaAs and arsenic metal (As°) targets were irradiated with 136 μA and 165 μA beam current possessing an initial Linac energy of 117 MeV. A total of 3.77 ± 0.1 GBq (102 ± 3 mCi) of 72 Se was produced from a GaAs target at a calculated target entrance energy of 105.4 MeV, and 13.8 ± 0.3 GBq (373 ± 8 mCi) of 72 Se from an As° target at a calculated incident energy of 49.5 MeV irradiated for 116.5 h and 68.9 h, respectively.

43 PARTICLE ACCELERATORS↗
DOE OSTI2018

Evaluation of 72 Se/ 72 As generator and production of 72 Se for supplying 72 As as a potential PET imaging radionuclide

Here, positron-emitting 72 As is the PET imaging counterpart for beta-emitting 77 As. Its parent, no carrier added (n.c.a.) 72 Se, was produced for a 72 Se/ 72 As generator by irradiating an enriched 7° Ge metal-graphite target via the 70 Ge(α, 2 n) 72 Se reaction. Target dissolution used a fast, environmentally friendly method with 93% radioactivity recovery. Chromatographic parameters of the 72 Se/ 72 As generator were evaluated, the eluted n.c.a. 72 As was characterized with a phantom imaging study, and the previously reported trithiol and aryl-dithiol ligand systems were radiolabeled with the separated n.c.a. 72 As in high yield.

43 PARTICLE ACCELERATORS↗
DOE OSTI2018

A trithiol bifunctional chelate for 72,77 As: A matched pair theranostic complex with high in vivo stability

Trithiol chelates are suitable for labeling radioarsenic ( 72 As: 2.49 MeV β + , 26 h; 77 As: 0.683 MeV β - , 38.8 h) to form potential theranostic radiopharmaceuticals for PET imaging and therapy. In this paper, to investigate the in vivo stability of trithiol chelates complexed with no carrier added (nca) radioarsenic, a bifunctional trithiol chelate was developed, and conjugated to bombesin(7–14)NH 2 as a model peptide. A trithiol-BBN(7–14)NH 2 bioconjugate and its arsenic complex were synthesized and characterized. The trithiol-BBN(7–14)NH 2 conjugate was radiolabeled with 77 As, its in vitro stability assessed, and biodistribution studies were performed in CF-1 normal mice of free [ 77 As]arsenate and 77 As-trithiol- BBN(7–14)NH 2 . The trithiol-BBN(7–14)NH 2 conjugate, its precursors and its As-trithiol-BBN(7–14)NH 2 complex were fully characterized. Radiolabeling studies with nca 77 As resulted in over 90% radiochemical yield of 77 As-trithiol-BBN, which was stable for over 48 h. Biodistribution studies were performed with both free [ 77 As]arsenate and Sep-Pak® purified 77 As-trithiol-BBN(7–14)NH 2 . Compared to the fast renal clearance of free [ 77 As]arsenate, 77 As-trithiol-BBN(7–14)NH 2 demonstrated increased retention with clearance mainly through the hepatobiliary system, consistent with the lipophilicity of the 77 As-trithiol-BBN(714)NH 2 complex. Finally, the combined in vitro stability of 77 As-trithiol-BBN(7–14)NH 2 and the biodistribution results demonstrate its high in vivo stability, making the trithiol a promising platform for developing radioarsenic-based theranostic radiopharmaceuticals.

38 RADIATION CHEMISTRY, RADIOCHEMISTRY, AND NUCLEA↗
DOE OSTI2018

Changes in iron availability in Arabidopsis are rapidly sensed in the leaf vasculature and impaired sensing leads to opposite transcriptional programs in leaves and roots

The OLIGOPEPTIDE TRANSPORTER 3 (OPT3) has recently been identified as a component of the systemic network mediating iron (Fe) deficiency responses in Arabidopsis. Reduced expression of OPT3 induces an over accumulation of Fe in roots and leaves, due in part by an elevated expression of the IRON-REGULATED TRANSPORTER 1. Here we show however, that opt3 leaves display a transcriptional program consistent with an Fe overload, suggesting that Fe excess is properly sensed in opt3 leaves and that the OPT3-mediated shoot-to-root signaling is critical to prevent a systemic Fe overload. We also took advantage of the tissue-specific localization of OPT3, together with other Fe-responsive genes, to determine the timing and location of early transcriptional events during Fe limitation and resupply. Our results show that the leaf vasculature responds more rapidly than roots to both Fe deprivation and resupply, suggesting that the leaf vasculature is within the first tissues that sense and respond to changes in Fe availability. Our data highlight the importance of the leaf vasculature in Fe homeostasis by sensing changes in apoplastic levels of Fe coming through the xylem and relaying this information back to roots via the phloem to regulate Fe uptake at the root level.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2017

Scale-up of high specific activity 186g Re production using graphite-encased thick 186 W targets and demonstration of an efficient target recycling process

Production of high specific activity 186g Re is of interest for development of theranostic radiopharmaceuticals. Previous studies have shown that high specific activity 186g Re can be obtained by cyclotron irradiation of enriched 186 W via the 186 W(d,2n) 186g Re reaction, but most irradiations were conducted at low beam currents and for short durations. In this paper, enriched 186 W metal targets were irradiated at high incident deuteron beam currents to demonstrate production rates and contaminants produced when using thick targets. Full-stopping thick targets, as determined using SRIM, were prepared by uniaxial pressing of powdered natural abundance W metal or 96.86% enriched 186 W metal encased between two layers of graphite flakes for target material stabilization. An assessment of structural integrity was made on each target preparation. To assess the performance of graphite-encased thick 186 W metal targets, along with the impact of encasing on the separation chemistry, targets were first irradiated using a 22 MeV deuteron beam for 10 min at 10, 20, and 27 μA, with an estimated nominal deuteron energy of 18.7 MeV on the 186 W target material (after energy degradation correction from top graphite layer). Gamma-ray spectrometry was performed post EOB on all targets to assess production yields and radionuclidic byproducts. The investigation also evaluated a method to recover and recycle enriched target material from a column isolation procedure. Material composition analyses of target materials, pass-through/wash solutions and recycling process isolates were conducted with SEM, FTIR, XRD, EDS and ICP-MS spectrometry. Finally, to demonstrate scaled-up production, a graphite-encased 186 W target made from recycled 186 W was irradiated for ~2 h with 18.7 MeV deuterons at a beam current of 27 μA to provide 0.90 GBq (24.3 mCi) of 186g Re, decay-corrected to the end of bombardment. ICP-MS analysis of the isolated 186g Re solution provided data that indicated the specific activity of 186g Re in this scaled-up production run was 2.6±0.5 GBq/μg (70±10 Ci/mg).

38 RADIATION CHEMISTRY, RADIOCHEMISTRY, AND NUCLEA↗
DOE OSTI2017

Bulk production and evaluation of high specific activity 186g Re for cancer therapy using enriched 186 WO 3 targets in a proton beam

Rhenium-186 g (t 1/2 = 3.72 d) is a β– emitting isotope suitable for theranostic applications. Current production methods rely on reactor production by way of the reaction 185 Re(n,γ) 186g Re, which results in low specific activities limiting its use for cancer therapy. Production via charged particle activation of enriched 186 W results in a 186g Re product with a much specific activity, allowing it to be used more broadly for targeted radiotherapy applications. Furthermore, this targets the unmet clinical need for more efficient radiotherapeutics.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2017

In vivo transport of three radioactive [ 18 F]-fluorinated deoxysucrose analogs by the maize sucrose transporter ZmSUT1

Sucrose transporter (SUT) proteins translocate sucrose across cell membranes; however, mechanistic aspects of sucrose binding by SUTs are not well resolved. Specific hydroxyl groups in sucrose participate in hydrogen bonding with SUT proteins. We previously reported that substituting a radioactive fluorine-18 [ 18 F] at the C-60 position within the fructosyl moiety of sucrose did not affect sucrose transport by the maize (Zea mays) ZmSUT1 protein. To determine how 18 F substitution of hydroxyl groups at two other positions within sucrose, the C-10 in the fructosyl moiety or the C-6 in the glucosyl moiety, impact sucrose transport, we synthesized 10-[F 18 ]fluoro-10-deoxysucrose and 6-[F 18 ]fluoro-6-deoxysucrose ([ 18 F] FDS) analogs. In this work, each [ 18 F]FDS derivative was independently introduced into wild-type or sut1 mutant plants, which are defective in sucrose phloem loading. All three (10-, 60-, and 6-) [ 18 F]FDS derivatives were efficiently and equally translocated, similarly to carbon-14 [ 14 C]-labeled sucrose. Hence, individually replacing the hydroxyl groups at these positions within sucrose does not interfere with substrate recognition, binding, or membrane transport processes, and hydroxyl groups at these three positions are not essential for hydrogen bonding between sucrose and ZmSUT1. [ 18 F]FDS imaging afforded several advantages compared to [ 14 C]-sucrose detection. We calculated that 10-[ 18 F]FDS was transported at approximately a rate of 0.90 ± 0.15 m.h-1 in wild-type leaves, and at 0.68 ± 0.25 m.h-1 in sut1 mutant leaves. Collectively, our data indicated that [ 18 F]FDS analogs are valuable tools to probe sucrose-SUT interactions and to monitor sucrose transport in plants.

59 BASIC BIOLOGICAL SCIENCES↗