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Cutler, Cathy S.

Publications and source records attributed to Cutler, Cathy S..

13 records
All sourcesNASA NTRSDOE OSTI
DOE OSTI2024

“Production of High Specific Activity 155 Tb, 161 Tb and 203 Pb for Research and Clinical Applications: Effective Target Design, Target Material Recycling and Radioisotope Separation”

Radioisotopes are essential for the development and application of radiopharmaceuticals that target specific diseases, such as cancer, offering unique potential for precision medicine. The growing demand for theranostic radioisotopes underscores their critical role in personalized medicine, where they enhance diagnostic imaging, minimize patient radiation exposure, and improve targeted tissue uptake, particularly in receptor- and antigen-directed therapies. The theranostic pair terbium-155 (diagnostic) and terbium-161 (therapeutic) holds significant promise for advancing individualized, targeted, and dosimetry-driven radiotherapies. However, the United States currently lacks routine and reliable production of these isotopes. This project made significant progress toward addressing this supply issue by developing production and separation methods for terbium-155 and terbium-161 while also training the next generation of the nuclear and radiochemistry workforce. This grant also strengthened collaboration between scientists at the University of Washington, the University of Missouri and Brookhaven National Laboratory. The research effort focused on evaluating target preparation methods, optimizing irradiation parameters, and refining isolation processes. In addition, the project provided extensive hands-on training to graduate students and postdoctoral fellows, equipping them with expertise in radioisotope production technologies and fostering the growth of the nuclear science workforce.

07 ISOTOPE AND RADIATION SOURCES↗
DOE OSTI2024

Development of a SnO 2 -based 44 Ti/ 44 Sc generator for medical applications

Towards application of 44 Sc for diagnostic nuclear medicine, a 44 Ti/ 44 Sc generator based on an inorganic resin has been evaluated. Unlike other radionuclide generators used for medical applications, the long-term retention of the parent 44 Ti is vital due to its long half life. In this work, tin dioxide (SnO 2 ), a robust inorganic-based resin, has been synthesized and used as the stationary phase for a 44 Ti/ 44 Sc generator. The sorption behavior of 44 Ti/ 44 Sc was tested on SnO 2 with varying acids, concentrations, and times. Preliminary batch study results showed >88 % 44 Ti retention to the resin at lower acid concentrations (0.05 M HNO 3 and 0.05 M HCl). A pilot generator was evaluated for a year, demonstrating 85.3 ± 2.8 % 44 Sc elution yields and 0.71 ± 0.14 % 44 Ti breakthrough in 5 M HNO 3 . Based on capacity studies, a 7.4 MBq (200 µCi) upscaled generator system was constructed for further evaluation of the SnO 2 resin stability and the efficacy of the eluted 44 Sc for radiolabeling. 44 Sc could be regularly eluted from this generator in 5 M HNO 3 with an overall average radiochemical yield 84.7 ± 9.5 %. Post-elution processing of the 44 Sc with DGA-normal resin removed all 44 Ti present and allowed for high 44 Sc-DOTA labeling yields of 94.2 ± 0.5 %. Overall, SnO 2 has been shown to be a viable material for a 44 Ti/ 44 Sc generator.

07 ISOTOPE AND RADIATION SOURCES↗
DOE OSTI2024

FLUKA simulation validation to measure the beam energy of a cyclotron

FLUKA is a fully integrated particle physics MonteCarlo simulation package which has many applications in high energy experimental physics and engineering. When using a cyclotron for medical radionuclide production, it is important to know that the beam energy is suitable to cause the intended nuclear reaction and minimize unwanted impurities. Here, this work focuses on the comparison of FLUKA as a tool to measure the beam energy of a cyclotron with experimental results using the method of stacked copper foils interspaced by an aluminum degrader. We compared two methods to determine the activity ratio: determining the activity in each foil using the experimentally measured cross-sections from the National Nuclear Data Center (NNDC) cross-section data and calculating the activity in the two Cu foils using the FLUKA program. These results were compared to those reported by Gagnon et al., 2011. The FLUKA results gave energy measurements that were different than the true energy by a percentage in the range of 2.4% to 13%, suggesting that FLUKA is not recommended for pre-calculating the cyclotron beam energy using these low Z materials without experimental confirmation. It also confirms that the experimental cross-section data from the NNDC database is superior for this application giving energy values that ranged from 0.1% to 1.6% from the true energy.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗
DOE OSTI2022

Evaluation of hydroxamate-based resins towards a more clinically viable 44 Ti/ 44 Sc radionuclide generator

For this research, several hydroxamate-based resins were synthesized and tested for use in 44 Ti/ 44 Sc generator systems in small scale experiments (740 kBq 44 Ti). The most promising resin was tested further in larger scale generator studies (37 MBq). This resin displayed impressive retention of 44 Ti over several elutions, and high quantities of 44 Sc were obtained in small volumes of dilute HCl eluents. Initial radiolabeling experiments were conducted and demonstrated the possibility of direct radiolabeling of the generator produced 44 Sc with DOTA.

07 ISOTOPE AND RADIATION SOURCES↗
DOE OSTI2022

Inorganic resins enable the increased purification efficiency of 82 Sr from rubidium targets for use in PET imaging isotope production

The 82 Sr/ 82 Rb generator system has found use in positron emission tomography (PET) imaging of myocardial perfusion. 82 Sr is produced by proton irradiation of Rb metal/RbCl salt followed by chemical separation. Inorganic ion-exchangers were synthesized by hydrothermal methods and evaluated for the purification of accelerator-produced 82Sr from a RbCl target and co-produced impurities like 75 Se, Fe, Cr, and Ni. A process consisting of removal of bulk RbCl using sodium nonatitanate (SNT), then removal of remaining tracers of Rb and Se using poorly crystalline silicotitanate (pCST) is suitable for 82 Sr separation and achieves higher purity of 82 Sr vs. commonly used organic resins.

43 PARTICLE ACCELERATORS↗
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

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 OSTI2022

67 Cu Production Capabilities: A Mini Review

Is the 67 Cu production worldwide feasible for expanding preclinical and clinical studies? How can we face the ingrowing demands of this emerging and promising theranostic radionuclide for personalized therapies? This review looks at the different production routes, including the accelerator- and reactor-based ones, providing a comprehensive overview of the actual 67 Cu supply, with brief insight into its use in non-clinical and clinical studies. In addition to the most often explored nuclear reactions, this work focuses on the 67 Cu separation and purification techniques, as well as the target material recovery procedures that are mandatory for the economic sustainability of the production cycle. The quality aspects, such as radiochemical, chemical, and radionuclidic purity, with particular attention to the coproduction of the counterpart 64 Cu, are also taken into account, with detailed comparisons among the different production routes. Future possibilities related to new infrastructures are included in this work, as well as new developments on the radiopharmaceuticals aspects.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2021

Measurement and modeling of proton-induced reactions on arsenic from 35 to 200 MeV

72 As is a promising positron emitter for diagnostic imaging that can be employed locally using a 72 Se generator. However, current reaction pathways to 72 Se have insufficient nuclear data for efficient production using regional 100–200 MeV high-intensity proton accelerators. In order to address this deficiency, stacked-target irradiations were performed at LBNL, LANL, and BNL to measure the production of the 72 Se/ 72 As positron emission tomography (PET) generator system via 75 As (p, x) between 35 and 200 MeV. This work provides the most well-characterized excitation function for 75 As ( p , 4 n ) 72 Se starting from threshold. Additional focus was given to report the first measurements of 75 As (p, x) 68 Ge and bolster an already robust production capability for the highly valuable 68 Ge/ 68 Ga PET generator. Thick target yield comparisons with prior established formation routes to both generators are made. In total, high-energy proton-induced cross sections are reported for 55 measured residual products from 75 As, nat Cu , and nat Ti targets, where the latter two materials were present as monitor foils. These results were compared with literature data as well as the default theoretical calculations of the nuclear model codes TALYS, COH, EMPIRE, and ALICE. Reaction modeling at these energies is typically unsatisfactory due to few prior published data and many interacting physics models. Therefore, a detailed assessment of the talys code was performed with simultaneous parameter adjustments applied according to a standardized procedure. Particular attention was paid to the formulation of the two-component exciton model in the transition between the compound and preequilibrium regions, with a linked investigation of level density models for nuclei off of stability and their impact on modeling predictive power. This paper merges experimental work and evaluation techniques for high-energy charged-particle isotope production in an extension to an earlier study of this kind.

43 PARTICLE ACCELERATORS↗
DOE OSTI2021

Investigating high-energy proton-induced reactions on spherical nuclei: Implications for the preequilibrium exciton model

A number of accelerator-based isotope production facilities utilize $100-200$ MeV proton beams due to the high production rates enabled by high-intensity beam capabilities and the greater diversity of isotope production brought on by the long range of high-energy protons. However, nuclear reaction modeling at these energies can be challenging because of the interplay between different reaction modes and a lack of existing guiding cross section data. A Tri-lab collaboration has been formed between the Lawrence Berkeley, Los Alamos, and Brookhaven National Laboratories to address these complexities by characterizing charged-particle nuclear reactions relevant to the production of established and novel radioisotopes. In the inaugural collaboration experiments, stacked-targets of niobium foils were irradiated at the Brookhaven Linac Isotope Producer ($E_p=200$ MeV) and the Los Alamos Isotope Production Facility ($E_p=100$ MeV) to measure $^{93}$Nb(p,x) cross sections between $50-200$ MeV. The results were compared with literature data as well as the default calculations of the nuclear model codes TALYS, CoH, EMPIRE, and ALICE. The default code predictions largely failed to reproduce the measurements. Therefore, we developed a standardized procedure, which determines the reaction model parameters that best reproduce the most prominent reaction channels in a physically justifiable manner. Overall, the primary focus of the procedure was to determine the best parameterization for the pre-equilibrium two-component exciton model. This modeling study revealed a trend towards a relative decrease for internal transition rates at intermediate proton energies ($E_p=20-60$ MeV) in the current exciton model as compared to the default values. The results of this work are instrumental for the planning, execution, and analysis essential to isotope production.

43 PARTICLE ACCELERATORS↗
DOE OSTI2020

Global Issues of Radiopharmaceutical Access and Availability: a Nuclear Medicine Global Initiative Project

The Nuclear Medicine Global Initiative (NMGI) was formed in 2012 by 13 international organizations to promote human health by advancing the field of nuclear medicine and molecular imaging by supporting the practice and application of nuclear medicine. The first project focused on standardization of administered activities in pediatric nuclear medicine and resulted in two manuscripts. For its second project the NMGI chose to explore issues impacting on access and availability of radiopharmaceuticals around the world. Methods: Information was obtained by survey responses from 35 countries on available radioisotopes, radiopharmaceuticals and kits for diagnostic and therapeutic use. Issues impacting on access and availability of radiopharmaceuticals in individual countries were also identified. Results: Detailed information on radiopharmaceuticals utilized in each country, and sources of supply, was evaluated. Responses highlighted problems in access particularly due to the reliance on a sole provider, regulatory issues and reimbursement, as well as issues of facilities and workforce particularly in low- and middle-income countries. Conclusion: Finally, strategies to address access and availability of radiopharmaceuticals are outlined, to enable timely and equitable patient access to nuclear medicine procedures worldwide. In the face of disruptions to global supply chains by the COVID-19 outbreak, renewed focus on ensuring reliable supply of radiopharmaceuticals is a major priority for nuclear medicine practice globally.

43 PARTICLE ACCELERATORS↗