FP-CIT Research Articles

Identification of Activation Isotopes in a CS-30 Cyclotron Vault

A CS-30 cyclotron has been in operation at King Faisal Specialist Hospital and Research Center (KFSHRC) since 1982. The CS-30 cyclotron has been used to produce medical radioisotopes for positron emission tomography (PET) and single-photon emission computed tomography (SPECT). Some of the nuclear reactions of radionuclide production are associated with the intense release of a wide range of fast neutrons. In this work, we investigated the radionuclides produced from neutron interactions with the cyclotron facility walls. Activation isotopes were determined by performing gamma ray spectrometry utilizing a high-purity germanium (HPGe) detector. The major radionuclides found were 152Eu, 154Eu, 134Cs, 65Zn and 60Co. Activation isotope accumulation had increased the dose rate inside the facility. The surface dose rates were measured at all of the surrounding walls. The maximum surface dose rate was found to be 1.2 µSv/h, which is much lower than the permissible occupational exposure of 15 µSv/h based daily 5 work hours.

Impact of Tumor Burden on Normal Organ Distribution in Patients Imaged with CXCR4-Targeted [68Ga]Ga-PentixaFor PET/CT

BackgroundCXCR4-directed positron emission tomography/computed tomography (PET/CT) has been used as a diagnostic tool in patients with solid tumors. We aimed to determine a potential correlation between tumor burden and radiotracer accumulation in normal organs.MethodsNinety patients with histologically proven solid cancers underwent CXCR4-targeted [68Ga]Ga-PentixaFor PET/CT. Volumes of interest (VOIs) were placed in normal organs (heart, liver, spleen, bone marrow, and kidneys) and tumor lesions. Mean standardized uptake values (SUVmean) for normal organs were determined. For CXCR4-positive tumor burden, maximum SUV (SUVmax), tumor volume (TV), and fractional tumor activity (FTA, defined as SUVmean x TV), were calculated. We used a Spearman's rank correlation coefficient (ρ) to derive correlative indices between normal organ uptake and tumor burden.ResultsMedian SUVmean in unaffected organs was 5.2 for the spleen (range, 2.44 – 10.55), 3.27 for the kidneys (range, 1.52 – 17.4), followed by bone marrow (1.76, range, 0.84 – 3.98), heart (1.66, range, 0.88 – 2.89), and liver (1.28, range, 0.73 – 2.45). No significant correlation between SUVmax in tumor lesions (ρ ≤ 0.189, P ≥ 0.07), TV (ρ ≥ -0.204, P ≥ 0.06) or FTA (ρ ≥ -0.142, P ≥ 0.18) with the investigated organs was found.ConclusionsIn patients with solid tumors imaged with [68Ga]Ga-PentixaFor PET/CT, no relevant tumor sink effect was noted. This observation may be of relevance for therapies with radioactive and non-radioactive CXCR4-directed drugs, as with increasing tumor burden, the dose to normal organs may remain unchanged.

A simple, reliable and accurate approach for assessing [131I]-capsule activity leading to significant reduction of radiation exposure of medical staff during radioiodine therapy

PurposeAccording to German law, the [131I]-capsule activity has to be checked in the context of radioiodine therapy (RIT) immediately before application. The measurement leads to significant radiation exposure of the medical personnel, especially of their hands. We aimed to establish a method for estimating [131I]-capsule activity by measuring the dose rate (DR) at contact of the delivered lead closed container carrying the [131I]-capsules and to evaluate radiation exposure in comparison to conventional [131I]-capsule measurement using a dose calibrator. MethodsDR on the surface of the closed lead container was measured at two locations and correlated linearly with the [131I]-capsule activity measured in a dose calibrator to create calibrating curves. The hand and whole body (effective) doses were determined with official dose meters during validation of our method in clinical practice. ResultsThe determination coefficients (R2) of linear calibration curves were greater than 0.9974. The total relative uncertainty for estimating [131I]-capsule activity with our method was <±7.5% which is lower than the uncertainty of the nominal activity and quite close to the threshold limit for the maximum allowed uncertainty of ± 5% for measuring activity in radioactive drugs. The reduction of the hand dose caused by our method was 97% compared with the conventional measurements of the [131I]-capsules in a dose calibrator. ConclusionMeasuring DR on the surface of the closed lead containers enables the [131I]-capsules activity to be estimated simply, reliably and with sufficient accuracy leading to significant reduction of the radiation exposure for the medical staff.

Evaluation of the permissible 99Mo activity in the KL-15 cask in the design of transportation and process scheme

The demand for the use of radioactive isotopes in medicine is increasing with each coming year necessitating the increased output of radionuclide products. One of the most widely spread radionuclides used in medicine is technetium-99m (99mТс) (Feasibility of producing molybdenum-99 2015, NEA 2012, The Supply of Medical Radioisotopes 2015). The very short 99mТс life (6-hour half-life) requires its production directly on the site of medical treatment. This is achieved using molybdenum-technetium generators (Kodina and Krasikova 2014, Technical Reports No. NF-T-5.4. 2013, Technetium-99 Generator 2021) loaded with molybdenum-99 (99Мо), which uninterruptedly decays (half-life of 66 hours) yielding 99mTc. Close attention must be paid in the course of production of molybdenum-technetium generators to radiation safety during transportation of 99Мо on the territory of the manufacturing facility. The main measure for ensuring radiation safety during transportation of 99Мо is the application of special packaging kits. The Karpov Institute of Physical Chemistry JSC uses a wide range of packaging kits of types A and B for transportation of radioactive materials on the territory of the manufacturer with design features providing the required level of radiation safety. In particular, the KL-15 shipping cask loaded/unloaded from the top is used for onsite transportation of 99Мо for charging molybdenum-technetium generators. The maximum permissible activity of 99Мо is not specified in the passport of the KL-15 cask. Planned construction of a radionuclide production shop in accordance with GMP requirements will require the increase of output of target radionuclides by several times. The above considerations necessitated the evaluation of the maximum permissible activity of 99Мо planned to be transported in KL-15 casks. No other type of standard casks can be used because of their outside dimensions prohibiting the unloading of 99Мо inside the “hot” chamber. Calculation and experimental evaluation of permissible 99Мо activity during transportation inside the KL-15 cask was performed. The paper presents the calculated evaluation of the maximum permissible activity of 99Мо in a KL-15 cask to ensure the radiation exposure of personnel of group A working with the cask not exceeding the established level at the enterprise (80 μSv per shift) and not requiring the use of additional measures and means of protection. The results of the work allow us drawing the conclusion that the KL-15 cask ensures the required level of radiation safety with up to 241 Ki of 99Мо loaded in the cask.

Tungsten-Based Hybrid Composite Shield for Medical Radioisotope Defense.

The shielding performance of shielding clothing is typically improved by increasing the shielding material content, but this lowers the tensile strength of the material. The weight and wearability of the shielding suit are also adversely affected. Important considerations when developing shielding fabric are thickness and flexibility to allow the wearer sufficient mobility. Insufficient thickness lowers the shielding performance, whereas excessive thickness decreases the flexibility of the garment. This study aimed to develop a composite shield that reproduces the shielding performance and meets the flexibility of the process technology. The new shield was manufactured by combining two layers: the shielding fabric fabricated from tungsten wire and a shielding sheet produced by mixing a polymer (PDMS) with tungsten powder. These two shields were bonded to develop a double hybrid composite. Compared with the existing shielding sheet (produced from lead equivalent of 0.55 mmPb), the shielding performance of the hybrid composite shield improved by approximately 17% on average and the tensile strength was 53% higher. The hybrid composite shield has a thickness of 1.35 ± 0.02 mm and delivers the same shielding performance as the lead equivalent. The new hybrid composite shield offers higher wearer mobility while shielding against radiation exposure in medical institutions.

Production cross sections of 47Sc via alpha-particle-induced reactions on natural calcium up to 29 MeV

Production cross sections of a medical radioisotope 47Sc via alpha-particle-induced reactions on natural calcium were measured up to 29 MeV. The stacked-foil activation technique and gamma-ray spectrometry were adopted for the experiment. Cross sections of simultaneously formed radionuclides 46,44m,44g,43Sc and 47Ca were also determined. Physical yields of the alpha-particle-induced reactions on natCa and 44Ca were deduced from the measured cross sections.

Combination of compressed sensing-based iterative reconstruction and offset acquisition for I-123 FP-CIT SPECT: a simulation study

Objective(s):The purpose of this study was to validate undersampled single-photon emission computed tomography (SPECT) imaging using a combination of compressed sensing (CS) iterative reconstruction (CS-IR) and offset acquisition.Methods:Three types of numerical phantoms were used to evaluate image quality and quantification derived from CS with offset acquisition. SPECT images were reconstructed using filtered back-projection (FBP), maximum likelihood-expectation maximization (ML-EM), CS-IR, and CS-IR with offset acquisition. The efficacy of CS-IR with offset acquisition was examined in terms of spatial resolution, aspect ratio (ASR), activity concentration linearity, contrast, percent coefficient of variation (%CV), and specific binding ratio (SBR).Results:The full widths at half maximum remained unchanged as the number of projections decreased in CS-IR with offset acquisition. Changes in ASRs and linearities of count density were observed for ML-EM and CS-IR from undersampled projections. The %CV obtained by CS-IR with offset acquisition was substantially lower than that obtained by ML-EM and CS-IR. There were no significant differences between the %CVs obtained from 60 projections by CS-IR with offset acquisition and from 120 projections by FBP. Although the SBRs for CS-IR with offset acquisition tended to be slightly lower than for FBP, the SBRs for CS-IR with offset acquisition did not change with the number of projections.Conclusions:CS-IR with offset acquisition can provide good image quality and quantification compared with a commonly used SPECT reconstruction method, especially from undersampled projection data. Our proposed method could shorten overall SPECT acquisition times, which would benefit patients and enable quantification with dynamic SPECT acquisitions.

The Investigation of Proton Cyclotron Production Cross-Section for Some Medical Radioisotopes

The Investigation of Proton Cyclotron Production Cross-Section for Some Medical Radioisotopes

SNMMI Clinical Trials Network Research Series for Technologists: Clinical Research Primer—Regulatory Process, Part I: How and When Radiopharmaceuticals Can Be Used

CE credit: For CE credit, you can access the test for this article, as well as additional JNMT CE tests, online at https://www.snmmilearningcenter.org Complete the test online no later than March 2025. Your online test will be scored immediately. You may make 3 attempts to pass the test and must answer 75% of the questions correctly to receive Continuing Education Hour (CEH) credit. Credit amounts can be found in the SNMMI Learning Center Activity. SNMMI members will have their CEH credit added to their VOICE transcript automatically; nonmembers will be able to print out a CE certificate upon successfully completing the test. The online test is free to SNMMI members; nonmembers must pay $15.00 by credit card when logging onto the website to take the test.The radiopharmaceutical development and approval process in the United States has changed dramatically over the past decade with the emergence of several new and exciting diagnostic and therapeutic drugs. This impressive expansion is a direct result of the symbiotic relationship that exists between drug development, clinical research, and improved regulatory guidance. The correlative increase in clinical research has introduced diverse opportunities for newcomers in medical and scientific professions. Knowing how to successfully navigate the clinical research process can be challenging for a novice. The pathway is highly regulated and, with the addition of radiopharmaceuticals, may be confusing and daunting. Moreover, very little clinical research education and training is provided in the typical collegiate curricula for these new initiates. This article will familiarize the reader with the U.S. regulatory process by providing basic definitions and understanding of how and when radiopharmaceuticals can be used in clinical research, including those involving investigational new drug applications and radioactive drug research committees. A later article will expand the reader's clinical research knowledge by focusing on the identity and role of the institutional review board.

Mechanisms Responsible for Adsorption of Molybdate ions on Alumina for the Production of Medical Radioisotopes

Abstract In this work, the mechanisms responsible for the adsorption of molybdate ions on alumina are investigated using in-depth surface analyses of alumina specimens immersed in solutions containing different molybdate ions at different pH values. The obtained results reveal that when alumina is immersed in an acidic solution containing molybdate ions, the hydroxyl groups present on the surface are removed to generate positively charged sites, and molybdate ions (MoO42− or AlMo6O24H63−) are adsorbed via an electrostatic interaction. Alumina dissolves slightly in an acidic solution to form AlMo6O24H63−, which is more easily desorbed than MoO42−. Furthermore, the enhancement in the Mo adsorption or desorption property may be achieved by enriching the surface of the alumina adsorbent with many –OH groups and optimizing Mo solution to adsorb molybdate ions on alumina as MoO42− ions. These findings will assist researchers in engineering more efficient and stable alumina-based adsorbents for molybdenum adsorption used in medical radioisotope (99Mo/99mTc) generators.

125. Dynamic PET facilitated Pharmacokinetic Modeling and High-dose Rifampin Regimens for Staphylococcus aureus Orthopedic Implant Associated Infections: Bench to Bedside

125. Dynamic PET facilitated Pharmacokinetic Modeling and High-dose Rifampin Regimens for <i>Staphylococcus aureus</i> Orthopedic Implant Associated Infections: Bench to Bedside

191. High-Dose Rifampin-containing Regimens for the Treatment of TB Meningitis

191. High-Dose Rifampin-containing Regimens for the Treatment of TB Meningitis

Correlation of Dopaminergic Denervation and the Progression of Autonomic Dysfunctions in Different Clinical Subtypes of Parkinson's Disease.

Background Autonomic dysfunctions occur in the early stage of Parkinson's disease (PD) and impact the quality of life during the progression of the disease. In this study, we evaluated the serial progression of autonomic dysfunctions between different subtypes of a prospective PD cohort. Materials and Methods From the Parkinson's Progression Markers Initiative (PPMI) database, 325 PD patients (age: 61.2 ± 9.7, M : F = 215 : 110) were enrolled. Patients were subgrouped into tremor-dominant (TD), indeterminate, and postural instability and gait disorder (PIGD) subtypes. The progression of autonomic dysfunctions and dopaminergic denervation from I-123 FP-CIT SPECT images of each group were analyzed and compared at baseline, 12 months, 24 months, and 48 months of follow-up periods. Results The SCOPA-AUT score of the indeterminate subtype was significantly higher than that of the TD subtype (P < 0.05) at baseline and was significantly higher than that of both TD and PIGD subtypes (P < 0.05) at 48 months. The indeterminate subtype had the most significant correlation between the aggravation of dopaminergic denervation in I-123 FP-CIT SPECT images and the increase of SCOPA-AUT scores during 48 months of follow-up (r = 0.56, P < 0.01). Conclusions Autonomic dysfunctions were most severe in the indeterminate subtype throughout the 48 months of the follow-up period, with a significant correlation with dopaminergic denervation. We suggest a positive relationship between dopaminergic denervation and autonomic dysfunctions of the indeterminate subtype, beginning from the early stage of PD.

Production of medical radioisotope 167Tm by photonuclear reactions on natural ytterbium

Formation of Yb and Tm radioisotopes upon irradiation of ytterbium of natural isotopic composition by bremsstrahlung photons with energies up to 55 MeV was studied. The yield of the medical radionuclide 167Tm was (7.8 ± 1.1) × 103 Bq × μA-1 × h−1 × cm2 × g−1. Thulium radioisotopes were separated from irradiated ytterbium target by extraction chromatography on the LN Resin sorbent in nitric media. Efficient separation of tracer amounts of thulium from tens of milligrams of ytterbium could be achieved. The method can be of practical importance for the production of 167Tm when using a 168Yb enriched target.

Terbium Medical Radioisotope Production: Laser Resonance Ionization Scheme Development.

Terbium (Tb) is a promising element for the theranostic approach in nuclear medicine. The new CERN-MEDICIS facility aims for production of its medical radioisotopes to support related R&D projects in biomedicine. The use of laser resonance ionization is essential to provide radioisotopic yields of highest quantity and quality, specifically regarding purity. This paper presents the results of preparation and characterization of a suitable two-step laser resonance ionization process for Tb. By resonance excitation via an auto-ionizing level, the high ionization efficiency of 53% was achieved. To simulate realistic production conditions for Tb radioisotopes, the influence of a surplus of Gd atoms, which is a typical target material for Tb generation, was considered, showing the necessity of radiochemical purification procedures before mass separation. Nevertheless, a 10-fold enhancement of the Tb ion beam using laser resonance ionization was observed even with Gd:Tb atomic ratio of 100:1.

A generic gas chromatography method for determination of residual solvents in PET radiopharmaceuticals

A novel gas chromatography (GC) method for quantitation of volatile organic compounds (VOCs) in 18F- and 11C-radiopharmaceuticals listed in the European Pharmacopoeia (Ph. Eur.) was proposed. Optimized chromatographic parameters were used for separation of ethanol, acetone, acetonitrile, tetrahydrofuran (THF), dibromomethane (DBM), 2-dimethylaminoethanol (deanol), N,N-dimethylformamide (DMF) and dimethyl sulfoxide (DMSO) which could be detected in radioactive drug samples. The calculated peak resolutions (RS) were higher than 2.0 at ethanol concentration of up to 11 m/m%. Reproducible results could be obtained using base deactivated fused silica wool as packing material of inlet liner. Validation parameters showed excellent linearity (r2 ≥0.9998) in the range from 10 to at least 120% of concentration limit of solvents. The accuracy was determined as recovery of concentrations which ranged from 99.3% to 103.8%. Additionally, the relative standard deviation (RSD) of each solvent for inter-day and intra-day precision were in the range of 0.5–4.2% and 0.4–4.4%, respectively. The limit of quantitation (LOQ) for ethanol, acetone, acetonitrile, THF, DBM, deanol, DMF and DMSO was 0.48, 0.42, 0.43, 0.46, 4.35, 0.73, 0.68 and 0.50 mg/L, respectively. The developed procedure was successively applied for quantitation of ethanol, acetone, acetonitrile and deanol in radioactive drug samples of [11C]methionine, [11C]choline, 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) and O-(2-[18F]fluoroethyl)-L-tyrosine ([18F]FET). The proposed GC method applying flame ionization detection (FID) could be adapted in routine quality control of most frequently used positron emission tomography (PET) radiopharmaceuticals to perform the determination of residual solvents with analysis time of 12 min

Precision Interventional Brachytherapy: A Promising Strategy Toward Treatment of Malignant Tumors.

Precision interventional brachytherapy is a radiotherapy technique that combines radiation therapy medicine with computer network technology, physics, etc. It can solve the limitations of conventional brachytherapy. Radioactive drugs and their carriers change with each passing day, and major research institutions and enterprises worldwide have conducted extensive research on them. In addition, the capabilities of interventional robotic systems are also rapidly developing to meet clinical needs for the precise delivery of radiopharmaceuticals in interventional radiotherapy. This study reviews the main radiopharmaceuticals, drug carriers, dispensing and fixation technologies, and interventional robotic precision delivery systems used in precision brachytherapy of malignant tumors. We then discuss the current needs in the field and future development prospects in high-precision interventional brachytherapy.

Investigation of a Possible Material-Saving Approach of Sputtering Techniques for Radiopharmaceutical Target Production

Magnetron sputtering (MS) is a relatively new deposition technique, which is being considered among the cyclotron solid target (CST) manufacturing options now available, aiming at the medical radioisotopes yield for radiopharmaceutical production. However, the intrinsic high material losses during the deposition process do not permit its use with extremely expensive target materials, such as isotopically enriched metals/oxides. In this study, R&amp;D technology for a new recovering shield is instead proposed to assess the dissipation of target material during the sputtering processes and, thus, an estimate of the material recovery that may be feasible and the related amount. The weight-loss analysis method is used to assess the material losses level inside the chamber during processing. In all tests carried out, a high-purity copper (99.99%) was used as a target material. As a result of this study, the material distribution for both magnetron and diode sputtering depositions can be calculated. The feasibility of the ultra-thick coatings growing, devoted to CST production, is demonstrated.

D2B antibody and its scFvD2B fragment in nanomedicine: promising tools in the theranostics of prostate cancer

Prostate cancer (PC) is ranked the sixth deadliest cancers among men. If PC is diagnosed at metastasised stages, traditional surgery and radiation therapy have limitations. In the last few decades, antibody therapy has emerged to deliver radioactive drugs to any metastatic PC tumours; thus, improving theranostics results and prolonged patient’s survival via effective targeting of prostate specific membrane antigens (PSMA). Full length anti-PSMA antibody, D2B, and its single chain variable fragment, scFvD2B, have been extensively studied as naked or combined with nanoparticles (NPs) in targeted antibody therapy. Such a combination is considered a current hotspot in research as a means to enhance the delivery, binding specificity, and stability of therapeutic or diagnostic agents. In this review, we summarise and compare data from studies published between 1993 & 2021 to highlight the major outputs from in vivo and in vitro applications of D2B and scFvD2B antibodies in PC theranostics. Special focus is set on gold nanoparticles (AuNPs) as a delivery vehicle given their unique physicochemical and biological properties. Our conclusion supports the use of AuNPs-scFvD2B conjugates in future biomedical approaches.

Manufacturing LEU-foil annular target in Brazil

Molybdenum-99 is the most important isotope because its daughter isotope, technetium-99m, has been the most used medical radioisotope. The primary method used to produce Mo-99 derives from the fission of U-235 incorporated in so-called irradiation targets. Two routes are being developed to make Mo-99 by fissioning with low enriched uranium (LEU) fuel. The first adopts UAlx-Al dispersion plate targets. The second uses uranium metal foil annular targets. The significant advantage of uranium foil targets over UAlx-Al dispersion targets is the high density of uranium metal. This work presents the experience obtained in the development of the uranium metal annular target manufacturing steps. An innovative method to improve the procedure for assembling the uranium foil on the tubular target was presented. The experience attained will help the future production of Mo-99 in Brazil through the target irradiation in the Brazilian Multipurpose Reactor (RMB).