Facile Preparation of Samarium Carbonate-Polymethacrylate Microspheres as a Neutron-Activatable Radioembolic Agent for Hepatic Radioembolization.

Radioembolization shows great potential as a treatment for intermediate- and advanced-stage liver cancer. However, the choices of radioembolic agents are currently limited, and hence the treatment is relatively costly compared to other approaches. In this study, a facile preparation method was developed to produce samarium carbonate-polymethacrylate [152Sm2(CO3)3-PMA] microspheres as neutron activatable radioembolic microspheres for hepatic radioembolization. The developed microspheres emits both therapeutic beta and diagnostic gamma radiations for post-procedural imaging. The 152Sm2(CO3)3-PMA microspheres were produced from commercially available PMA microspheres through the in situ formation of 152Sm2(CO3)3 within the pores of the PMA microspheres. Physicochemical characterization, gamma spectrometry and radionuclide retention assay were performed to evaluate the performance and stability of the developed microspheres. The mean diameter of the developed microspheres was determined as 29.30 ± 0.18 µm. The scanning electron microscopic images show that the spherical and smooth morphology of the microspheres remained after neutron activation. The 153Sm was successful incorporated into the microspheres with no elemental and radionuclide impurities produced after neutron activation, as indicated by the energy dispersive X-ray analysis and gamma spectrometry. Fourier transform infrared spectroscopy confirmed that there was no alteration to the chemical groups of the microspheres after neutron activation. After 18 h of neutron activation, the microspheres produced an activity of 4.40 ± 0.08 GBq.g-1. The retention of 153Sm on the microspheres was greatly improved to greater than 98% over 120 h when compared to conventionally radiolabeling method at ~85%. The 153Sm2(CO3)3-PMA microspheres achieved suitable physicochemical properties as theragnostic agent for hepatic radioembolization and demonstrated high radionuclide purity and 153Sm retention efficiency in human blood plasma.

Evaluation of Therapeutic Efficacy and Imaging Capabilities of 153Sm2O3-Loaded Polystyrene Microspheres for Intra-Tumoural Radionuclide Therapy of Liver Cancer Using Sprague-Dawley Rat Model.

Introduction: Neutron-activated samarium-153-oxide-loaded polystyrene ([153Sm]Sm2O3-PS) microspheres has been developed in previous study as a potential theranostic agent for hepatic radioembolization. In this study, the therapeutic efficacy and diagnostic imaging capabilities of the formulation was assessed using liver cancer Sprague-Dawley (SD) rat model. Methods: Twelve male SD rats (150-200 g) that implanted with N1-S1 hepatoma cell line orthotopically were divided into two groups (study versus control) to monitor the tumour growth along 60 days of treatment. The study group received an intra-tumoural injection of approximately 37 MBq of [153Sm]Sm2O3-PS microspheres, while control group received an intra-tumoural injection of 0.1 mL of saline solution. A clinical single photon emission computed tomography/computed tomography (SPECT/CT) system was used to scan the rats at Day 5 post-injection to investigate the diagnostic imaging capabilities of the microspheres. All rats were monitored for change in tumour volume using a portable ultrasound system throughout the study period. Histopathological examination (HPE) was performed after the rats were euthanized at Day 60. Results: At Day 60, no tumour was observed on the ultrasound images of all rats in the study group. In contrast, the tumour volumes in the control group were 24-fold larger compared to baseline. Statistically significant difference was observed in tumour volumes between the study and control groups (p < 0.05). The SPECT/CT images clearly displayed the location of [153Sm]Sm2O3-PS in the liver tumour of all rats at Day 5 post-injection. Additionally, the [153Sm]Sm2O3-PS microspheres was visible on the CT images and this has added to the benefits of 153Sm as a CT contrast agent. The HPE results showed that the [153Sm]Sm2O3-PS microspheres remained concentrated at the injection site with no tumour cells observed in the study group. Conclusions: Neutron-activated [153Sm]Sm2O3-PS microspheres demonstrated excellent therapeutic and diagnostic imaging capabilities for theranostic treatment of liver cancer in a SD rat model. Further studies with different animal and tumour models are planned to validate this finding.

Exploring the Potential of High-Molar-Activity Samarium-153 for Targeted Radionuclide Therapy with [153Sm]Sm-DOTA-TATE.

Samarium-153 is a promising theranostic radionuclide, but low molar activities (Am) resulting from its current production route render it unsuitable for targeted radionuclide therapy (TRNT). Recent efforts combining neutron activation of 152Sm in the SCK CEN BR2 reactor with mass separation at CERN/MEDICIS yielded high-Am 153Sm. In this proof-of-concept study, we further evaluated the potential of high-Am 153Sm for TRNT by radiolabeling to DOTA-TATE, a well-established carrier molecule binding the somatostatin receptor 2 (SSTR2) that is highly expressed in gastroenteropancreatic neuroendocrine tumors. DOTA-TATE was labeled with 153Sm and remained stable up to 7 days in relevant media. The binding specificity and high internalization rate were validated on SSTR2-expressing CA20948 cells. In vitro biological evaluation showed that [153Sm]Sm-DOTA-TATE was able to reduce CA20948 cell viability and clonogenic potential in an activity-dependent manner. Biodistribution studies in healthy and CA20948 xenografted mice revealed that [153Sm]Sm-DOTA-TATE was rapidly cleared and profound tumor uptake and retention was observed whilst these were limited in normal tissues. This proof-of-concept study showed the potential of mass-separated 153Sm for TRNT and could open doors towards wider applications of mass separation in medical isotope production.

Production cross sections of samarium-153 and -145 via alpha-particle-induced reactions on natural neodymium.

Production cross sections of 153,145Sm via alpha-particle-induced reactions on natNd were measured up to 23 MeV. The stacked-foil activation technique and high-resolution gamma-ray spectrometry were adopted for the measurement. The obtained cross sections were compared with the literature data and the TENDL-2019 and TENDL-2021 values. Physical thick target yields of the two radionuclides were derived from the measured cross sections.

ANALGESIC EFFECT OF VARIOUS RADIOPHARMACEUTICALS IN THE COMPLEX TREATMENT OF METASTATIC BONE DISEASE. / ZNEBOLIuVAL'NYI VPLYV RIZNYKh RADIOFARMPREPARATIV U KOMPLEKSNOMU LIKUVANNI METASTATYChNOGO URAZhENNIa KISTOK.

OBJECTIVE: The study objective was to investigate and compare the effectiveness of different radiopharmaceuticalsin the treatment of metastatic bone disease. MATERIALS AND METHODS: Cancer patients (n = 150, average age (55 ± 11.6) years, 95 females, 55 males) having gotvarious primary tumors and metastatic bone disease were given medical treatment at the Department of NuclearMedicine of the National Institute of Cancer. The 153Sm, 32Р, and 89Sr radiopharmaceutical agents produced by the«Radiopreparats¼ enterprise (Republic of Uzbekistan) and Radioisotope Centre Polatom (National Centre for NuclearResearch, Poland) were administered to the patients. There were cases of breast cancer (n = 75), prostate cancer(n = 45), lung cancer (n = 10), kidney cancer (n = 4), cervical cancer (n = 5), and rectosigmoid cancer (n = 11) amongthe treated subjects. In 135 patients (90 %) the bone metastases were detected by osteoscintigraphy with 99мTc- mo-nodiphosphonate. In 15 cases the diagnosis of metastatic bone disease was verified by other radiology methods. RESULTS: The pain intensity rating scale (LACOMED) was used to assay the analgesic effect of various radiopharma-ceuticals in metastatic bone disease. Results of treatment with 32P, 89Sr, and 153Sm were included in a comparativeanalysis procedure. It was established that the level of pain syndrome ranged from 7-8 points on the LACOMED scalebefore treatment. Upon administration of radionuclide therapy the level of pain was reduced down to 3-5 points,namely with 32P therapy it has decreased by 30.7 %, with 89Sr by 33.2 %, and with 153Sm by 41.5 % respectively. Timepattern of 153Sm analgesic effectiveness was studied depending on the number of treatment sessions. The best valueof analgesic effect of 153Sm was registered after the first treatment session with a tendency to decrease after the sec-ond and significantly lower analgesic effects after the third session. Tolerance of 153Sm was rated on the CTCNCA (v)4.3 scale. The best tolerance was peculiar to 153Sm corresponding to the «good¼ level according to a point assess-ment. When using 89Sr the drug tolerance was lower, not requiring however the drug discontinuation. The 32P radio-pharmaceutical featured the lowest tolerance approaching the «satisfactory¼ rating. In 11 patients upon that theside effects were found significantly impairing the patient's status, accordingly some extra measures were required.No decision to cancel the drug administration was made. CONCLUSIONS: Radionuclide therapy with 153Sm-oxabiphor agent can be used in the complex treatment of metastat-ic bone disease in cancer patients having got tumors of different localization. 153Sm-oxabiphor is the most effectiveand best tolerable radiopharmaceutical agent in the pain treatment in metastatic bone disease in comparison with32P and 89Sr preparations (р < 0.05).

Production of Sm-153 With Very High Specific Activity for Targeted Radionuclide Therapy.

Samarium-153 (153Sm) is a highly interesting radionuclide within the field of targeted radionuclide therapy because of its favorable decay characteristics. 153Sm has a half-life of 1.93 d and decays into a stable daughter nuclide (153Eu) whereupon ß- particles [E = 705 keV (30%), 635 keV (50%)] are emitted which are suitable for therapy. 153Sm also emits γ photons [103 keV (28%)] allowing for SPECT imaging, which is of value in theranostics. However, the full potential of 153Sm in nuclear medicine is currently not being exploited because of the radionuclide's limited specific activity due to its carrier added production route. In this work a new production method was developed to produce 153Sm with higher specific activity, allowing for its potential use in targeted radionuclide therapy. 153Sm was efficiently produced via neutron irradiation of a highly enriched 152Sm target (98.7% enriched, σth = 206 b) in the BR2 reactor at SCK CEN. Irradiated target materials were shipped to CERN-MEDICIS, where 153Sm was isolated from the 152Sm target via mass separation (MS) in combination with laser resonance enhanced ionization to drastically increase the specific activity. The specific activity obtained was 1.87 TBq/mg (≈ 265 times higher after the end of irradiation in BR2 + cooling). An overall mass separation efficiency of 4.5% was reached on average for all mass separations. Further radiochemical purification steps were developed at SCK CEN to recover the 153Sm from the MS target to yield a solution ready for radiolabeling. Each step of the radiochemical process was fully analyzed and characterized for further optimization resulting in a high efficiency (overall recovery: 84%). The obtained high specific activity (HSA) 153Sm was then used in radiolabeling experiments with different concentrations of 4-isothiocyanatobenzyl-1,4,7,10-tetraazacyclododecane tetraacetic acid (p-SCN-Bn-DOTA). Even at low concentrations of p-SCN-Bn-DOTA, radiolabeling of 0.5 MBq of HSA 153Sm was found to be efficient. In this proof-of-concept study, we demonstrated the potential to combine neutron irradiation with mass separation to supply high specific activity 153Sm. Using this process, 153SmCl3 suitable for radiolabeling, was produced with a very high specific activity allowing application of 153Sm in targeted radionuclide therapy. Further studies to incorporate 153Sm in radiopharmaceuticals for targeted radionuclide therapy are ongoing.

Experiments with a prototype titanium hot cavity surface ionization source intended for electromagnetic separation of radioactive samarium and other lanthanide elements.

This paper reports experimental results of a prototype titanium surface ionization source. For the first time, a lanthanide ion beam has been produced with a surface ionizer composed completely of titanium metal. Titanium does not readily activate with neutron irradiation. This offers the potential for inserting an ion source made of titanium directly into a reactor with a pre-loaded non-radioactive lanthanide target. This seamlessly integrates target irradiation with isotope separation, eliminating post irradiation sample manipulation. Samarium ion beam currents up to 960 nA have been produced in an off-line test bench equipped with rudimentary beam optics. This is a crucial step toward the development of an ionization source adopted for the electromagnetic isotope separator (EMIS) facility, which has been designed for high throughput separations of radioactive 153Sm and other lanthanides of interest in the field of nuclear medicine. The ion current and important factors affecting the performance of the ion source, such as the ionizer temperature and thermal gradient, are discussed. The experimental results are presented together with a discussion of future modifications to optimize the overall surface ionization source performance.

Knee radiosynovectomy with 153Sm-hydroxyapatite compared to 90Y-hydroxyapatite: initial results of a prospective trial.

INTRODUCTION: Radiosynovectomy (RS) with 90Y-hydroxyapatite (90Y-HyA) aims to control knee hemarthrosis in hemophiliac patients to prevent secondary arthropathy. However, knee RS using 153Sm-hydroxyapatite (153Sm-HyA) is considered less suitable due to the lower average soft tissue range and energy of 153Sm for large joints, such as the knees. PURPOSE: The objective of this investigation was to assess the efficacy and safety of knee RS with 153Sm-HyA, compared to 90Y-HyA. METHODS: Forty patients were prospectively assigned to undergo knee RS with 153Sm-HyA (n = 19) or with 90Y-HyA (n = 21). The frequency of hemarthrosis episodes before and after treatment were compared. RESULTS: After six months of knee RS, 153Sm-HyA and 90Y-HyA promoted a similar reduction of hemarthrosis episodes (50% and 66.7%, respectively). However, after 12 months of knee RS, the reduction of hemarthrosis episodes was significantly (p = 0.037) higher using 153Sm-HyA (87.5%) compared to 90Y-HyA (50.0%). This discrepancy was more pronounced (p = 0.002) for 153Sm-HyA compared to 90Y-HyA in adults/adolescents. CONCLUSION: Knee radiosynovectomy with 153Sm-HyA is safe, reduces hemarthrosis episodes after 12 months of treatments, especially in adults/adolescents and even with grades III/IV arthropathy, similar to 90Y-HyA. 90Y-HyA seems to promote better hemarthrosis control in small children.

Systemic Radiotherapy of Bone Metastases With Radionuclides.

Treatments of bone metastases using radionuclides are now well established in oncology. It is also a field that continues to develop. This article reviews the evidence base that led to the approval of strontium-89 and samarium-153 ethylenediaminetetramethylene phophanate (EDTMP) for the palliation of pain from bone metastases, as well as the evidence for the use of radium-223 in metastatic castrate-resistant prostate cancer. Efforts to optimise treatments and improve response rates, either by safely increasing the radiation dose to bone metastases or by combining treatment with non-radiation-based therapies, are discussed. In addition, the development of both alpha- and beta-particle-emitting radiopharmaceuticals designed to target prostate-specific membrane antigen are reviewed.

Optimization of Scatter Correction Method in Samarium-153 Single-photon Emission Computed Tomography using Triple-Energy Window: A Monte Carlo Simulation Study.

PURPOSE: In single-photon emission computed tomography imaging, the presence of scatter degrades image quality. The goal of this study is to optimize the main- and sub-energy windows for triple-energy window (TEW) method using Monte Carlo SImulating Medical Imaging Nuclear Detectors (SIMIND) code for samarium-153 (Sm-153) imaging. MATERIALS AND METHODS: The comparison is based on the Monte Carlo simulation data with the results estimated using TEW method. Siemens Symbia gamma-camera equipped with low-energy high-resolution collimator was simulated for Sm-153 point source located in seven positions in water cylindrical phantom. Three different main-energy window widths (10%, 15%, and 20%) and three different sub-energy window widths (2, 4, and 6 keV) were evaluated. We compared the true scatter fraction determined by SIMIND and scatter fraction estimated using TEW scatter correction method at each position. In order to evaluate the image quality, we used the full width at half maximum (FWHM) computed on the PSF and image contrast using Jaszczak phantom. RESULTS: The scatter fraction using TEW method is similar to the true scatter fraction for 20% of the main-energy window and 6 keV sub-energy windows. For these windows, the results show that the resolution and contrast were improved. CONCLUSION: TEW method could be a useful scatter correction method to remove the scatter event in the image for Sm-153 imaging.