Development and physicochemical characterization of a biodegradable microspheres formulation loaded with samarium-153 and doxorubicin for chemo-radioembolization of liver tumours.

Transarterial chemoembolization (TACE) and transarterial radioembolization (TARE) are promising treatments for unresectable liver tumours. Some recent studies suggested that combining TACE and TARE in one treatment course might improve treatment efficacy through synergistic cytotoxicity effects. Nonetheless, current formulations do not facilitate a combination of chemo- and radio-embolic agents in one delivery system. Therefore, this study aimed to synthesise a hybrid biodegradable microsphere loaded with both radioactive agent, samarium-153 (153 Sm) and chemotherapeutic drug, doxorubicin (Dox) for potential radio-chemoembolization of advanced liver tumours. 152 Sm and Dox-loaded polyhydroxybutyrate-co-3-hydroxyvalerate (PHBV) microspheres were prepared using water-in-oil-in-water solvent evaporation method. The microspheres were then sent for neutron activation in a neutron flux of 2 × 1012 n/cm2 /s. The physicochemical properties, radioactivity, radionuclide purity, 153 Sm retention efficiency, and Dox release profile of the Dox-153 Sm-PHBV microspheres were analysed. In addition, in vitro cytotoxicity of the formulation was tested using MTT assay on HepG2 cell line at 24 and 72 h. The mean diameter of the Dox-153 Sm-PHBV microspheres was 30.08 ± 2.79 µm. The specific radioactivity was 8.68 ± 0.17 GBq/g, or 177.69 Bq per microsphere. The 153 Sm retention efficiency was more than 99%, tested in phosphate-buffered saline (PBS) and human blood plasma over 26 days. The cumulative release of Dox from the microspheres after 41 days was 65.21 ± 1.96% and 29.96 ± 0.03% in PBS solution of pH 7.4 and pH 5.5, respectively. The Dox-153 Sm-PHBV microspheres achieved a greater in vitro cytotoxicity effect on HepG2 cells (85.73 ± 3.63%) than 153 Sm-PHBV (70.03 ± 5.61%) and Dox-PHBV (74.06 ± 0.78%) microspheres at 300 µg/mL at 72 h. In conclusion, a novel biodegradable microspheres formulation loaded with chemotherapeutic drug (Dox) and radioactive agent (153 Sm) was successfully developed in this study. The formulation fulfilled all the desired physicochemical properties of a chemo-radioembolic agent and achieved better in vitro cytotoxicity on HepG2 cells. Further investigations are needed to evaluate the biosafety, radiation dosimetry, and synergetic anticancer properties of the formulation.

Experimental assessment on feasibility of computed tomography-based thermometry for radiofrequency ablation on tissue equivalent polyacrylamide phantom.

Purpose: This study aimed to evaluate the effects of various computed tomography (CT) acquisition parameters and metal artifacts on CT number measurement for CT thermometry during CT-guided thermal ablation. Methods: The effects of tube voltage (100-140 kVp), tube current (20-250 mAs), pitch (0.6-1.5) and gantry rotation time (0.5, 1.0 s) as well as metal artifacts from a radiofrequency ablation (RFA) needle on CT number were evaluated using liver tissue equivalent polyacrylamide (PAA) phantom. The correlation between CT number and temperature from 37 to 80 °C was studied on PAA phantom using optimum CT acquisition parameters. Results: No statistical significant difference (p > 0.05) was found on CT numbers under the variation of different acquisition parameters for the same temperature setting. On the other hand, the RFA needle has induced metal artifacts on the CT images of up to 8 mm. The CT numbers decreased linearly when the phantom temperature increased from 37 to 80 °C. A linear regression analysis on the CT numbers and temperature suggested that the CT thermal sensitivity was -0.521 ± 0.061 HU/°C (R2 = 0.998). Conclusion: CT thermometry is feasible for temperature assessment during RFA with the current CT technology, which produced a high CT number reproducibility and stable measurement at different CT acquisition parameters. Despite being affected by metal artifacts, the CT-based thermometry could be further developed as a tissue temperature monitoring tool during CT-guided thermal ablation.

Optimal approach for complete liver tumor ablation using radiofrequency ablation: a simulation study.

PURPOSE: To investigate the effect of radiofrequency ablation (RFA) electrode trajectory on complete tumor ablation using computational simulation. MATERIAL AND METHODS: The RFA of a spherical tumor of 2.0 cm diameter along with 0.5 cm clinical safety margin was simulated using Finite Element Analysis software. A total of 86 points inside one-eighth of the tumor volume along the axial, sagittal and coronal planes were selected as the target sites for electrode-tip placement. The angle of the electrode insertion in both craniocaudal and orbital planes ranged from -90° to +90° with 30° increment. The RFA electrode was simulated to pass through the target site at different angles in combination of both craniocaudal and orbital planes before being advanced to the edge of the tumor. RESULTS: Complete tumor ablation was observed whenever the electrode-tip penetrated through the epicenter of the tumor regardless of the angles of electrode insertion in both craniocaudal and orbital planes. Complete tumor ablation can also be achieved by placing the electrode-tip at several optimal sites and angles. CONCLUSIONS: Identification of the tumor epicenter on the central slice of the axial images is essential to enhance the success rate of complete tumor ablation during RFA procedures.

Robotic-assisted thermal ablation of liver tumours.

OBJECTIVE: This study aimed to assess the technical success, radiation dose, safety and performance level of liver thermal ablation using a computed tomography (CT)-guided robotic positioning system. METHODS: Radiofrequency and microwave ablation of liver tumours were performed on 20 patients (40 lesions) with the assistance of a CT-guided robotic positioning system. The accuracy of probe placement, number of readjustments and total radiation dose to each patient were recorded. The performance level was evaluated on a five-point scale (5-1: excellent-poor). The radiation doses were compared against 30 patients with 48 lesions (control) treated without robotic assistance. RESULTS: Thermal ablation was successfully completed in 20 patients with 40 lesions and confirmed on multiphasic contrast-enhanced CT. No procedure related complications were noted in this study. The average number of needle readjustment was 0.8 ± 0.8. The total CT dose (DLP) for the entire robotic assisted thermal ablation was 1382 ± 536 mGy.cm, while the CT fluoroscopic dose (DLP) per lesion was 352 ± 228 mGy.cm. There was no statistically significant (p > 0.05) dose reduction found between the robotic-assisted versus the conventional method. CONCLUSION: This study revealed that robotic-assisted planning and needle placement appears to be safe, with high accuracy and a comparable radiation dose to patients. KEY POINTS: • Clinical experience on liver thermal ablation using CT-guided robotic system is reported. • The technical success, radiation dose, safety and performance level were assessed. • Thermal ablations were successfully performed, with an average performance score of 4.4/5.0. • Robotic-assisted ablation can potentially increase capabilities of less skilled interventional radiologists. • Cost-effectiveness needs to be proven in further studies.

Low-melting-point polymeric nanoshells for thermal-triggered drug release under hyperthermia condition.

PURPOSE: The aim of this paper was to synthesise core-shell nanostructures comprised of mesoporous silica core and a low melting-point polyethylene glycol (PEG) nanoshell with a sharp gel-liquid phase transition for rapid drug release at hyperthermia temperature range. MATERIALS AND METHODS: The phase transition behaviours of PEGs with molecular weights of 1000, 1500, and 2000 Da were analysed using differential scanning calorimetry (DSC) to determine the optimal formulation with phase transition in the hyperthermia range. The 'graft-to' method was employed to synthesise core-shell nanostructures using the selected PEG formulation. The drug loading and release behaviours of these nanocarriers were examined by ultra-violet visible spectroscopy (UV-Vis) using doxorubicin as a model drug. Magnetic resonance-guided focused ultrasound (MRgFUS) was also applied as a typical thermal modality to evaluate the rate of drug release from the core-shell nanostructures. RESULTS: The PEG molecular weight of 1500 Da presented the optimal phase transition temperature for thermal-triggered release under hyperthermia conditions. Drug release measurements at different temperatures using UV-Vis methods showed a 20.2 ± 4.3% leakage in aqueous solution at 37 °C after 30 min, while this value was significantly increased to 68.2 ± 3.7% at 50 °C. A 45.5 ± 3.1% drug release was also obtained after sonication of the drug-loaded nanoparticles for 5 × 20 s using MRgFUS. CONCLUSION: Although the ratio of drug leakage at physiological temperatures was relatively high, the sharp transition temperature, high loading efficiency, and fast drug release at hyperthermia temperature range could make these core-shell nanoparticles prominent for enhancing the efficacy of various hyperthermia modalities in the treatment of cancer tumours.

A new mechanism of thermal sensitivity for rapid drug release and low systemic toxicity in hyperthermia and thermal ablation temperature ranges.

PURPOSE: The aim of this paper was to introduce a new mechanism of thermal sensitivity in nanocarriers that results in a relatively low drug release at physiological temperature and rapid release of the encapsulated drug at hyperthermia and thermal ablation temperature range (40-60 °C). MATERIALS AND METHODS: The nanocarriers were synthesised by coating mesoporous silica nanoparticles with a thin layer of polyacrylamide. The low gelation temperature of the protective shell provides preferred routes for drug diffusion when the nanocarriers are heated within the hyperthermia temperature range. In order to determine the gelation point of polyacrylamide shell, differential scanning calorimetry was used. Various chemical, morphological, thermal, as well as drug loading capacities of these nanocarriers were characterised and their drug release behaviour was examined using magnetic resonance -guided focused ultrasound (MRgFUS). RESULTS: Drug release measurements at different temperatures using doxorubicin showed 11.5 ± 2.4% leakage in aqueous solution at 37 °C after 30 min, while this value was significantly increased to 67.6 ± 2.5% at 60 °C. A 39.2 ± 2.2% release of doxorubicin was also obtained due to the sonication of drug-loaded nanoparticles for 5 × 20 s using MRgFUS. CONCLUSION: The nanocarriers developed do not exhibit a sharp transition temperature. However, a relatively high loading efficiency as well as rapid drug release at thermal ablation temperature range makes these nanostructures promising candidates for application as adjuvants to various thermal modalities such as radiofrequency and high intensity focused ultrasound.

Robot-assisted radiofrequency ablation of primary and secondary liver tumours: early experience.

OBJECTIVE: Computed tomography (CT)-compatible robots, both commercial and research-based, have been developed with the intention of increasing the accuracy of needle placement and potentially improving the outcomes of therapies in addition to reducing clinical staff and patient exposure to radiation during CT fluoroscopy. In the case of highly inaccessible lesions that require multiple plane angulations, robotically assisted needles may improve biopsy access and targeted drug delivery therapy by avoidance of the straight line path of normal linear needles. METHODS: We report our preliminary experience of performing radiofrequency ablation of the liver using a robotic-assisted CT guidance system on 11 patients (17 lesions). RESULTS/CONCLUSION: Robotic-assisted planning and needle placement appears to have high accuracy, is technically easier than the non-robotic-assisted procedure, and involves a significantly lower radiation dose to both patient and support staff. KEY POINTS: • An early experience of robotic-assisted radiofrequency ablation is reported • Robotic-assisted RFA improves accuracy of hepatic lesion targeting • Robotic-assisted RFA makes the procedure technically easier with significant lower radiation dose.

Reusable heat-sensitive phantom for precise estimation of thermal profile in hyperthermia application.

PURPOSE: The emergence of thermal modalities has promoted the use of heat-sensitive phantoms for calibration, measurement, and verification purposes. However, development of durable phantoms with high precision ability to represent the temperature distribution remains a challenge. This study aims to introduce a reusable phantom that provides an accurate assessment of the heated region in various thermal modalities. MATERIALS AND METHODS: The phantom contains a thermochromic dye that is transparent blue at room temperature and becomes colourless after exceeding a threshold temperature. In order to determine the threshold temperature of the phantom, spectrophotometry analysis was performed. The various thermal (specific heat, thermal conductivity, melting point and latent heat of melting) and acoustic (sound speed, attenuation) properties of this phantom were measured and compared with those of the reference phantom without dye. The application of this phantom for radio-frequency and magnetic resonance guided focused ultrasound modalities was also examined. RESULTS: The spectrophotometry analysis showed a threshold temperature of 50 ± 3 °C for this phantom. The results also demonstrated a 6 °C difference between the onset and ending temperatures of the discolouration process. Moreover, the starting temperature of colouration during cooling was found to be 4 °C lower than the ending temperature of discolouration. The sound speed, attenuation, specific heat, thermal conductivity and melting point of the heat-sensitive phantom were statistically equal to those of the reference phantom; however, the latent heat, and onset temperature of the melting of the heat-sensitive phantom were decreased by addition of the dye. CONCLUSIONS: The developed phantom is applicable for accurate evaluation of temperature variations in various thermal modalities.

Tissue-mimicking gel phantoms for thermal therapy studies.

Tissue-mimicking phantoms that are currently available for routine biomedical applications may not be suitable for high-temperature experiments or calibration of thermal modalities. Therefore, design and fabrication of customized thermal phantoms with tailored properties are necessary for thermal therapy studies. A multitude of thermal phantoms have been developed in liquid, solid, and gel forms to simulate biological tissues in thermal therapy experiments. This article is an attempt to outline the various materials and techniques used to prepare thermal phantoms in the gel state. The relevant thermal, electrical, acoustic, and optical properties of these phantoms are presented in detail and the benefits and shortcomings of each type are discussed. This review could assist the researchers in the selection of appropriate phantom recipes for their in vitro study of thermal modalities and highlight the limitations of current phantom recipes that remain to be addressed in further studies.

Fluoroscopy assisted minimally invasive transplantation of allogenic mesenchymal stromal cells embedded in HyStem reduces the progression of nucleus pulposus degeneration in the damaged ntervertebral [corrected] disc: a preliminary study in rabbits.

This study was conducted to develop a technique for minimally invasive and accurate delivery of stem cells to augment nucleus pulposus (NP) in damaged intervertebral discs (IVD). IVD damage was created in noncontiguous discs at L4-L5 level; rabbits (N = 12) were randomly divided into three groups: group I treated with MSCs in HyStem hydrogel, group II treated with HyStem alone, and group III received no intervention. MSCs and hydrogel were administered to the damaged disc under guidance of fluoroscopy. Augmentation of NP was assessed through histological and MRI T2 mapping of the NP after eight weeks of transplantation. T2 weighted signal intensity was higher in group I than in groups II and III (P < 0.05). Disc height index showed maximum disc height in group I compared to groups II and III. Histological score of the degenerative index was significantly (P < 0.05) lower in group I (8.6 ± 1.8) than that in groups II (11.6 ± 2.3) and III (18.0 ± 5.7). Immunohistochemistry staining for collagen type II and aggrecan staining were higher in group I as compared to other groups. Our results demonstrate that the minimally invasive administration of MSCs in hyaluronan hydrogel (HyStem) augments the repair of NP in damaged IVD.

Intra-arterial allogeneic mesenchymal stem cells for critical limb ischemia are safe and efficacious: report of a phase I study.

BACKGROUND: Critical limb ischemia (CLI) caused by peripheral arterial disease is associated with significant morbidity and mortality. This condition is associated with a 30 % amputation rate as well as mortality levels which might be as high as 25 %. There is no pharmacological therapy available, but several reports have suggested that mesenchymal stem cells (MSCs) may be a useful therapeutic option. METHODS: This study, done at a university hospital, evaluated 13 patients for a phase I trial to investigate the safety and efficacy of intra-arterial MSCs in CLI patients. Eight patients with ten affected limbs were recruited for the study. As two patients (three limbs) died of ischemic cardiac events during the 6-month follow-up period, seven limbs were finally evaluated for the study. RESULTS: There was significant pain relief. Visual analog scale (VAS) scores decreased from 2.29 ± 0.29 to 0.5 ± 0.34 (p < 0.05), ankle brachial pressure index (ABPI) increased significantly from 0.56 ± 0.02 to 0.67 ± 0.021 (p < 0.01), and transcutaneous oxygen pressure (TcPO2) also increased significantly in the foot from 13.57 ± 3.63 to 38 ± 3.47. Similar improvement was seen in the leg as well as the thigh. There was 86 % limb salvage and six of seven ulcers showed complete or partial healing. CONCLUSION: It was concluded that intra-arterial MSCs could be safely administered to patients with CLI and was associated with significant therapeutic benefits.

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.

Cell therapy in critical limb ischemia: current developments and future progress.

Critical limb ischemia (CLI) is a syndrome manifested by ischemic rest pain, non-healing ulcers and tissue loss. CLI patients are at very high risk of amputation and experience poor physical function, leading to severe morbidity and mortality. The fundamental goal for CLI treatment is to relieve ischemic rest pain, heal ulcers, prevent limb loss and improve the quality of life, thereby extending the survival of the patient. Surgical or endovascular revascularization aimed at increasing blood flow is currently available for limb salvage in CLI. However, up to 30% of CLI patients are not suitable for such interventions because of high operative risk or unfavorable vascular anatomy. Therefore exploring new and more effective strategies for revascularization of ischemic limbs is imperative for the establishment of a viable therapeutic alternative. With the emergence of new approaches, this review describes up-to-date progress and developments in cell-based therapy as a novel and promising alternative for CLI treatment. Preliminary clinical data have established the safety, feasibility and efficacy of stem cells, and numerous studies are underway to consolidate this evidence further. However, significant hurdles remain to be addressed before this research can be responsibly translated to the bedside. In particular, we need better understanding of the behavior of cells post-transplantation and to learn how to control their survival and migration proliferation/differentiation in the hostile pathologic environment. Future research should focus on methods of isolation, optimal dosage, appropriate cell type, route of administration, role of tissue-derived factors and supportive endogenous stimulation.

Development of neutron-activated samarium-153-loaded polystyrene microspheres as a potential theranostic agent for hepatic radioembolization.

PURPOSE: Hepatic radioembolization is an effective minimally invasive treatment for primary and metastatic liver cancers. Yttrium-90 [90Y]-labelled resin or glass beads are typically used as the radioembolic agent for this treatment; however, these are not readily available in many countries. In this study, novel samarium-153 oxide-loaded polystyrene ([153Sm]Sm2O3-PS) microspheres were developed as a potential alternative to 90Y microspheres for hepatic radioembolization. METHODS: The [152Sm]Sm2O3-PS microspheres were synthesized using solid-in-oil-in-water solvent evaporation. The microspheres underwent neutron activation using a 1 MW open-pool research reactor to produce radioactive [153Sm]Sm2O3-PS microspheres via 152Sm(n,γ)153Sm reaction. Physicochemical characterization, gamma spectroscopy and in-vitro radionuclide retention efficiency were carried out to evaluate the properties and stability of the microspheres before and after neutron activation. RESULTS: The [153Sm]Sm2O3-PS microspheres achieved specific activity of 5.04 ± 0.52 GBq·g-1 after a 6 h neutron activation. Scanning electron microscopy and particle size analysis showed that the microspheres remained spherical with an average diameter of ~33 µm before and after neutron activation. No long half-life radionuclide and elemental impurities were found in the samples. The radionuclide retention efficiencies of the [153Sm]Sm2O3-PS microspheres at 550 h were 99.64 ± 0.07 and 98.76 ± 1.10% when tested in saline solution and human blood plasma, respectively. CONCLUSIONS: A neutron-activated [153Sm]Sm2O3-PS microsphere formulation was successfully developed for potential application as a theranostic agent for liver radioembolization. The microspheres achieved suitable physical properties for radioembolization and demonstrated high radionuclide retention efficiency in saline solution and human blood plasma.

Comparison of deep and moderate neuromuscular blockade in microwave ablation of liver tumours: a randomized-controlled clinical trial.

Microwave ablation (MWA) is gaining popularity for the treatment of small primary hepatocellular carcinoma and metastatic lesions especially if patients are not candidates for surgical resection. Deep neuromuscular blockade (DMB) is perceived to improve surgical working conditions compared to moderate neuromuscular blockade (MMB) but no studies have examined the same benefits in MWA of liver tumours. This study aimed to compare the clinical outcomes of DMB and MMB in MWA of liver tumours in terms of liver excursion, performance scores by the interventional radiologists and patients, requirements of additional muscle relaxants and complications. 50 patients were recruited and 45 patients (22 in MMB group, 23 in DMB group) completed the study. The mean liver excursion for the MMB group (1.42 ± 1.83 mm) was significantly higher than the DMB group (0.26 ± 0.38 mm) (p = 0.001). The mean Leiden-Surgical Rating Scale (L-SRS) rated by the two interventional radiologists were 4.5 ± 0.59 and 3.6 ± 0.85 for the DMB and MMB groups, respectively (p = 0.01). There was also statistically significant difference on patient satisfaction scores (0-10: Extremely Dissatisfied-Extremely Satisfied) between DMB (8.74 ± 1.1) and MMB (7.86 ± 1.25) groups (p = 0.01). 5 patients from MMB group and none from DMB group required bolus relaxant during the MWA procedure. Adverse events were also noted to be more severe in the MMB group. In conclusion, DMB significantly reduced liver excursion and movement leading to improved accuracy, safety and success in ablating liver tumour.

Laser-heated needle for biopsy tract ablation: In vivo study of rabbit liver biopsy.

PURPOSE: To investigate the efficacy of a newly-developed laser-heated core biopsy needle in the thermal ablation of biopsy tract to reduce hemorrhage after biopsy using in vivo rabbit's liver model. MATERIALS AND METHODS: Five male New Zealand White rabbits weighed between 1.5 and 4.0 kg were anesthetized and their livers were exposed. 18 liver biopsies were performed under control group (without tract ablation, n = 9) and study group (with tract ablation, n = 9) settings. The needle insertion depth (~3 cm) and rate of retraction (~3 mm/s) were fixed in all the experiments. For tract ablation, three different needle temperatures (100, 120 and 150 °C) were compared. The blood loss at each biopsy site was measured by weighing the gauze pads before and after blood absorption. The rabbits were euthanized immediately and the liver specimens were stained with hematoxylin-eosin (H&E) for further histopathological examination (HPE). RESULTS: The average blood loss in the study group was reduced significantly (p < 0.05) compared to the control group. The highest percentage of bleeding reduction was observed at the needle temperature of 150 °C (93.8%), followed by 120 °C (85.8%) and 100 °C (84.2%). The HPE results show that the laser-heated core biopsy needle was able to cause lateral coagulative necrosis up to 14 mm diameter along the ablation tract. CONCLUSION: The laser-heated core biopsy needle reduced hemorrhage up to 93.8% and induced homogenous coagulative necrosis along the ablation tract in the rabbits' livers. This could potentially reduce the risk of tumor seeding in clinical settings.

Neutron-activated biodegradable samarium-153 acetylacetonate-poly-L-lactic acid microspheres for intraarterial radioembolization of hepatic tumors.

BACKGROUND: Liver cancer is the 6th most common cancer in the world and the 4th most common death from cancer worldwide. Hepatic radioembolization is a minimally invasive treatment involving intraarterial administration of radioembolic microspheres. AIM: To develop a neutron-activated, biodegradable and theranostics samarium-153 acetylacetonate (153SmAcAc)-poly-L-lactic acid (PLLA) microsphere for intraarterial radioembolization of hepatic tumors. METHODS: Microspheres with different concentrations of 152SmAcAc (i.e., 100%, 150%, 175% and 200% w/w) were prepared by solvent evaporation method. The microspheres were then activated using a nuclear reactor in a neutron flux of 2 × 1012 n/cm2/s1, converting 152Sm to Samarium-153 (153Sm) via 152Sm (n, γ) 153Sm reaction. The SmAcAc-PLLA microspheres before and after neutron activation were characterized using scanning electron microscope, energy dispersive X-ray spectroscopy, particle size analysis, Fourier transform infrared spectroscopy, thermo-gravimetric analysis and gamma spectroscopy. The in-vitro radiolabeling efficiency was also tested in both 0.9% sodium chloride solution and human blood plasma over a duration of 550 h. RESULTS: The SmAcAc-PLLA microspheres with different SmAcAc contents remained spherical before and after neutron activation. The mean diameter of the microspheres was about 35 µm. Specific activity achieved for 153SmAcAc-PLLA microspheres with 100%, 150%, 175% and 200% (w/w) SmAcAc after 3 h neutron activation were 1.7 ± 0.05, 2.5 ± 0.05, 2.7 ± 0.07, and 2.8 ± 0.09 GBq/g, respectively. The activity of per microspheres were determined as 48.36 ± 1.33, 74.10 ± 1.65, 97.87 ± 2.48, and 109.83 ± 3.71 Bq for 153SmAcAc-PLLA microspheres with 100%, 150%, 175% and 200% (w/w) SmAcAc. The energy dispersive X-ray and gamma spectrometry showed that no elemental and radioactive impurities present in the microspheres after neutron activation. Retention efficiency of 153Sm in the SmAcAc-PLLA microspheres was excellent (approximately 99%) in both 0.9% sodium chloride solution and human blood plasma over a duration of 550 h. CONCLUSION: The 153SmAcAc-PLLA microsphere is potentially useful for hepatic radioembolization due to their biodegradability, favorable physicochemical characteristics and excellent radiolabeling efficiency. The synthesis of the formulation does not involve ionizing radiation and hence reducing the complication and cost of production.

Entrance surface dose and image quality: comparison of adult chest and abdominal X-ray examinations in general practitioner clinics, public and private hospitals in Malaysia.

This study was undertaken to compare the entrance surface dose (ESD) and image quality of adult chest and abdominal X-ray examinations conducted at general practitioner (GP) clinics, and public and private hospitals in Malaysia. The surveyed facilities were randomly selected within a given category (28 GP clinics, 20 public hospitals and 15 private hospitals). Only departmental X-ray units were involved in the survey. Chest examinations were done at all facilities, while only hospitals performed abdominal examinations. This study used the x-ray attenuation phantoms and protocols developed for the Nationwide Evaluation of X-ray Trends (NEXT) survey program in the United States. The ESD was calculated from measurements of exposure and clinical geometry. An image quality test tool was used to evaluate the low-contrast detectability and high-contrast detail performance under typical clinical conditions. The median ESD value for the adult chest X-ray examination was the highest (0.25 mGy) at GP clinics, followed by private hospitals (0.22 mGy) and public hospitals (0.17 mGy). The median ESD for the adult abdominal X-ray examination at public hospitals (3.35 mGy) was higher than that for private hospitals (2.81 mGy). Results of image quality assessment for the chest X-ray examination show that all facility types have a similar median spatial resolution and low-contrast detectability. For the abdominal X-ray examination, public hospitals have a similar median spatial resolution but larger low-contrast detectability compared with private hospitals. The results of this survey clearly show that there is room for further improvement in performing chest and abdominal X-ray examinations in Malaysia.

Preparation and In Vitro Evaluation of Neutron-Activated, Theranostic Samarium-153-Labeled Microspheres for Transarterial Radioembolization of Hepatocellular Carcinoma and Liver Metastasis.

INTRODUCTION: Transarterial radioembolization (TARE) has been proven as an effective treatment for unresectable liver tumor. In this study, neutron activated, 153Sm-labeled microspheres were developed as an alternative to 90Y-labeled microspheres for hepatic radioembolization. 153Sm has a theranostic advantage as it emits both therapeutic beta and diagnostic gamma radiations simultaneously, in comparison to the pure beta emitter, 90Y. METHODS: Negatively charged acrylic microspheres were labeled with 152Sm ions through electrostatic interactions. In another formulation, the Sm-labeled microsphere was treated with sodium carbonate solution to form the insoluble 152Sm carbonate (152SmC) salt within the porous structures of the microspheres. Both formulations were neutron-activated in a research reactor. Physicochemical characterization, gamma spectrometry, and radiolabel stability tests were carried out to study the performance and stability of the microspheres. RESULTS: The Sm- and SmC-labeled microspheres remained spherical and smooth, with a mean size of 35 µm before and after neutron activation. Fourier transform infrared (FTIR) spectroscopy indicated that the functional groups of the microspheres remained unaffected after neutron activation. The 153Sm- and 153SmC-labeled microspheres achieved activity of 2.53 ± 0.08 and 2.40 ± 0.13 GBq·g-1, respectively, immediate after 6 h neutron activation in the neutron flux of 2.0 × 1012 n·cm-2·s-1. Energy-dispersive X-ray (EDX) and gamma spectrometry showed that no elemental and radioactive impurities were present in the microspheres after neutron activation. The retention efficiency of 153Sm in the 153SmC-labeled microspheres was excellent (~99% in distilled water and saline; ~97% in human blood plasma), which was higher than the 153Sm-labeled microspheres (~95% and ~85%, respectively). CONCLUSION: 153SmC-labeled microspheres have demonstrated excellent properties for potential application as theranostic agents for hepatic radioembolization.