Radioactive Microspheres Research Articles

99mTc/90Y radiolabeled biodegradable gel microspheres for lung shutting fraction assessment and radioembolization in hepatocellular carcinoma theranostics

Transarterial radioembolization (TARE) is a well-established clinical therapy for the treatment of patients with intermediate to advanced hepatocellular carcinoma (HCC) or those who are ineligible for radical treatment. However, commercialized radioactive microspheres still have some issues, such as high density, complicated preparation, non-biodegradability. Furthermore, the use of different radioactive microspheres during TARE and lung shunt fraction assessment has led to inconsistencies in biodistribution in certain cases. This study employed biodegradable hyaluronic acid (HA) as the backbone and modified with bisphosphonate and methacrylic acid to prepare biodegradable gel microspheres (HAMS) using the water-in-oil emulsification and photo-crosslinking for labeling the diagnostic radionuclide of 99mTc and therapeutic radionuclide of 90Y. Both 99mTc radiolabeled HAMS (99mTc-HAMS) and radiolabeled 90Y-HAMS (90Y-HAMS) were highly efficient in radiolabeling and exhibited excellent radiostability in vitro and in vivo. 99mTc-HAMS are highly effective in assessing the LSF, while 90Y-HAMS, administered though TARE, are effective in inhibiting the growth of in situ HCC without any side effects. Both 99mTc-HAMS and 90Y-HAMS have promising clinical applications in HCC theranostics.

Quantitative CT imaging and radiation-absorbed dose estimations of 166Ho microspheres: paving the way for clinical application

BackgroundMicrobrachytherapy enables high local tumor doses sparing surrounding tissues by intratumoral injection of radioactive holmium-166 microspheres (166Ho-MS). Magnetic resonance imaging (MRI) cannot properly detect high local Ho-MS concentrations and single-photon emission computed tomography has insufficient resolution. Computed tomography (CT) is quicker and cheaper with high resolution and previously enabled Ho quantification. We aimed to optimize Ho quantification on CT and to implement corresponding dosimetry.MethodsTwo scanners were calibrated for Ho detection using phantoms and multiple settings. Quantification was evaluated in five phantoms and seven canine patients using subtraction and thresholding including influences of the target tissue, injected amounts, acquisition parameters, and quantification volumes. Radiation-absorbed dose estimation was implemented using a three-dimensional 166Ho specific dose point kernel generated with Monte Carlo simulations.ResultsCT calibration showed a near-perfect linear relation between radiodensity (HU) and Ho concentrations for all conditions, with differences between scanners. Ho detection during calibration was higher using lower tube voltages, soft-tissue kernels, and without a scanner detection limit. The most accurate Ho recovery in phantoms was 102 ± 11% using a threshold of mean tissue HU + (2 × standard deviation) and in patients 98 ± 31% using a 100 HU threshold. Thresholding allowed better recovery with less variation and dependency on the volume of interest compared to the subtraction of a single HU reference value. Corresponding doses and histograms were successfully generated.ConclusionCT quantification and dosimetry of 166Ho should be considered for further clinical application with on-site validation using radioactive measurements and intra-operative Ho-MS and dose visualizations.Relevance statementImage-guided holmium-166 microbrachytherapy currently lacks reliable quantification and dosimetry on CT to ensure treatment safety and efficacy, while it is the only imaging modality capable of quantifying high in vivo holmium concentrations.Key PointsLocal injection of 166Ho-MS enables high local tumor doses while sparing surrounding tissue.CT enables imaging-based quantification and radiation-absorbed dose estimation of concentrated Ho in vivo, essential for treatment safety and efficacy.Two different CT scanners and multiple acquisition and reconstruction parameters showed near-perfect linearity between radiodensity and Ho concentration.The most accurate Ho recoveries on CT were 102 ± 11% in five phantoms and 98 ± 31% in seven canine patients using thresholding methods.Dose estimations and volume histograms were successfully implemented for clinical application using a dose point kernel based on Monte Carlo simulations.Graphical

Development of Alginate-Based Biodegradable Radioactive Microspheres Labeled with Positron Emitter through Click Chemistry Reaction: Stability and PET Imaging Study.

Biodegradable radioactive microspheres labeled with positron emitters hold significant promise for diagnostic and therapeutic applications in cancers and other diseases, including arthritis. The alginate-based polymeric microspheres offer advantages such as biocompatibility, biodegradability, and improved stability, making them suitable for clinical applications. In this study, we developed novel positron emission tomography (PET) microspheres using alginate biopolymer radiolabeled with gallium-68 (68Ga) through a straightforward conjugation reaction. Polyethylenimine (PEI)-decorated calcium alginate microspheres (PEI-CAMSs) were fabricated and further modified using azadibenzocyclooctyne-N-hydroxysuccinimide ester (ADIBO-NHS). Subsequently, azide-functionalized NOTA chelator (N3-NOTA) was labeled with [68Ga]Ga to obtain [68Ga]Ga-NOTA-N3, which was then reacted with the surface-modified PEI-CAMSs using strain-promoted alkyne-azide cycloaddition (SPAAC) reaction to develop [68Ga]Ga-NOTA-PEI-CAMSs, a novel PET microsphere. The radiolabeling efficiency and radiochemical stability of [68Ga]Ga-NOTA-PEI-CAMSs were determined using the radio-instant thin-layer chromatography-silica gel (radio-ITLC-SG) method. The in vivo PET images were also acquired to study the in vivo stability of the radiolabeled microspheres in normal mice. The radiolabeling efficiency of [68Ga]Ga-NOTA-PEI-CAMSs was over 99%, and the microspheres exhibited high stability (92%) in human blood serum. PET images demonstrated the stability and biodistribution of the microspheres in mice for up to 2 h post injection. This study highlights the potential of biodegradable PET microspheres for preoperative imaging and targeted radionuclide therapy. Overall, the straightforward synthesis method and efficient radiolabeling technique provide a promising platform for the development of theranostic microspheres using other radionuclides such as 90Y, 177Lu, 188Re, and 64Cu.

Simplification strategies for a patient-specific CFD model of particle transport during liver radioembolization

BackgroundPatient-specific 3D computational fluid dynamics (CFD) simulations have been used previously to identify the impact of injection parameters (e.g. injection location, velocity, etc.) on the particle distribution and the tumor dose during transarterial injection of radioactive microspheres for treatment of hepatocellular carcinoma. However, these simulations are computationally costly, so we aim to evaluate whether these can be reliably simplified. MethodsWe identified and applied five simplification strategies (i.e. truncation, steady flow modelling, moderate and severe grid coarsening, and reducing the number of cardiac cycles) to a patient-specific CFD setup. Subsequently, we evaluated whether these strategies can be used to (1) accurately predict the CFD output (i.e. particle distribution and tumor dose) and (2) quantify the sensitivity of the model output to a specific injection parameter (injection flow rate). ResultsFor both accuracy and sensitivity purposes, moderate grid coarsening is the most reliable simplification strategy, allowing to predict the tumor dose with only a maximal deviation of 1.4 %, and a similar sensitivity (deviation of 0.7 %). The steady strategy performs the worst, with a maximal deviation in the tumor dose of 20 % and a difference in sensitivity of 10 %. ConclusionThe patient-specific 3D CFD simulations of this study can be reliably simplified by coarsening the grid, decreasing the computational time by roughly 45 %, which works especially well for sensitivity studies.

Ultrastable PLGA-Coated 177Lu-Microspheres for Radioembolization Therapy of Hepatocellular Carcinoma.

Transarterial radioembolization (TARE) is a highly effective localized radionuclide therapy that has been successfully used to treat hepatocellular carcinoma (HCC). Extensive research has been conducted on the use of radioactive microspheres (MSs) in TARE, and the development of ideal radioactive MSs is crucial for clinical trials and patient treatment. This study presents the development of a radioactive MS for TARE of HCC. These MSs, referred to as 177Lu-MS@PLGA, consist of poly(lactic-co-glycolic acid) (PLGA) copolymer and radioactive silica MSs, labeled with 177Lu and then coated with PLGA. It has an extremely high level of radiostability. Cellular experiments have shown that it can cause DNA double-strand breaks, leading to cell death. In vivo radiostability of 177Lu-MS@PLGA is demonstrated by microSPECT/CT imaging. In addition, the antitumor study has shown that TARE of 177Lu-MS@PLGA can effectively restrain tumor growth without harmful side effects. Thus, 177Lu-MS@PLGA exhibits significant potential as a radioactive MS for the treatment of HCC.

Ex Vivo Vascular Imaging and Perfusion Studies of Normal Kidney and Tumor Vasculature.

This work describes a comprehensive study of the vascular tree and perfusion characteristics of normal kidney and renal cell carcinoma. Methods: Nephrectomy specimens were perfused ex-vivo, and the regional blood flow was determined by infusion of radioactive microspheres. The vascular architecture was characterized by micronized barium sulphate infusion. Kidneys were subsequently sagitally sectioned, and autoradiograms were obtained to show the perfusate flow in relation to adjacent contact X-ray angiograms. Vascular resistance in defined tissue compartments was quantified, and finally, the tumor vasculature was 3D reconstructed via the micro-CT technique. Results show that the vascular tree of the kidney could be distinctly defined, and autoradiograms disclosed a high cortical flow. The peripheral resistance unit of the whole perfused specimen was 0.78 ± 0.40 (n = 26), while that of the renal cortex was 0.17 ± 0.07 (n = 15 with 114 samples). Micro-CT images from both cortex and medulla defined the vascular architecture. Angiograms from the renal tumors demonstrated a significant vascular heterogeneity within and between different tumors. A dense and irregular capillary network characterized peripheral tumor areas, whereas central parts of the tumors were less vascularized. Despite the dense capillarity, low perfusion through vessels with a diameter below 15 µm was seen on the autoradiograms. We conclude that micronized barium sulphate infusion may be used to demonstrate the vascular architecture in a complex organ. The vascular resistance was low, with little variation in the cortex of the normal kidney. Tumor tissue showed a considerable vascular structural heterogeneity with low perfusion through the peripheral nutritive capillaries and very poor perfusion of the central tumor, indicating intratumoral pressure exceeding the perfusion pressure. The merits and shortcomings of the various techniques used are discussed.

Selective internal radiation therapy segmentectomy: A new minimally invasive curative option for primary liver malignancies?

Transarterial radioembolization or selective internal radiation therapy (SIRT) has emerged as a minimally invasive approach for the treatment of tumors. This percutaneous technique involves the local, intra-arterial delivery of radioactive microspheres directly into the tumor. Historically employed as a palliative measure for liver malignancies, SIRT has gained traction over the past decade as a potential curative option, mirroring the increasing role of radiation segmentectomy. The latest update of the BCLC hepatocellular carcinoma guidelines recognizes SIRT as an effective treatment modality comparable to other local ablative methods, particularly well-suited for patients where surgical resection or ablation is not feasible. Radiation segmentectomy is a more selective approach, aiming to deliver high-dose radiation to one to three specific hepatic segments, while minimizing damage to surrounding healthy tissue. Future research efforts in radiation segmentectomy should prioritize optimizing radiation dosimetry and refining the technique for super-selective administration of radiospheres within the designated hepatic segments.

A microfluidic route for synthesis of scandium oxide microspheres, their characterization and neutron activation

Radioactive scandium-46 microspheres have applications in mapping flow in a chemical reactor through a technique known as radioactive particle tracking (RPT). In the present study a novel microfluidic method has been developed for synthesis of controlled size scandium oxide microspheres. An inline/in-situ mixing of the scandium precursor and gelling agents was implemented which makes the microfluidic platform amenable for truly continuous operation. Microspheres of size varying from 937 to 666 μm were produced by varying O/A ratio from 10 to 30. Perfectly spherical and monodispersed (PDI <10 %) microspheres were obtained at O/A 15 and beyond. The morphology, elemental composition, and structure of the microspheres were analysed by SEM, EDS and XRD, respectively. Subsequently the microspheres were irradiated with thermal neutrons in a nuclear reactor to obtain radioactive Sc-46 oxide microspheres. The activity produced on each Sc-46 microspheres with different sizes was in the range 19.5–34.0 MBq.

The Use of Microspheres for Cancer Embolization Therapy: Recent Advancements and Prospective.

Embolization therapy involving biomaterials has improved the therapeutic strategy for most liver cancer treatments. Developing biomaterials as embolic agents has significantly improved patients' survival rates. Various embolic agents are present in liquid agents, foam, particulates, and particles. Some of the most applied embolic agents are microparticles, such as microspheres (3D micrometer-sized spherical particles). Microspheres with added functionalities are currently being developed for effective therapeutic embolization. Their excellent properties of high surface area and capacity for being loaded with radionuclides and alternate active or therapeutic agents provide an additional advantage to overcome limitations from traditional cancer treatments. Microspheres (non-radioactive and radioactive) have been widely used and explored for localized cancer treatment. Non-radioactive microspheres exhibit improved clinical performance as drug delivery vehicles in chemotherapy due to their controlled and sustained drug release to the target site. They offer better flow properties and are beneficial for the ease of delivery via injection procedures. In addition, radioactive microspheres have also been exploited for use as an embolic platform in internal radiotherapy as an alternative to cancer treatment. This short review summarizes the progressive development of non-radioactive and radioactive embolic microspheres, emphasizing material characteristics. The use of embolic microspheres for various modalities of therapeutic arterial embolization and their impact on therapeutic performance are also discussed.

MIDOS: a novel stochastic model towards a treatment planning system for microsphere dosimetry in liver tumors.

Transarterial radioembolization (TARE) procedures treat liver tumors by injecting radioactive microspheres into the hepatic artery. Currently, there is a critical need to optimize TARE towards a personalized dosimetry approach. To this aim, we present a novel microsphere dosimetry (MIDOS) stochastic model to estimate the activity delivered to the tumor(s), normal liver, and lung. MIDOS incorporates adult male/female liver computational phantoms with the hepatic arterial, hepatic portal venous, and hepatic venous vascular trees. Tumors can be placed in both models at user discretion. The perfusion of microspheres follows cluster patterns, and a Markov chain approach was applied to microsphere navigation, with the terminal location of microspheres determined to be in either normal hepatic parenchyma, hepatic tumor, or lung. A tumor uptake model was implemented to determine if microspheres get lodged in the tumor, and a probability was included in determining the shunt of microspheres to the lung. A sensitivity analysis of the model parameters was performed, and radiation segmentectomy/lobectomy procedures were simulated over a wide range of activity perfused. Then, the impact of using different microspheres, i.e., SIR-Sphere®, TheraSphere®, and QuiremSphere®, on the tumor-to-normal ratio (TNR), lung shunt fraction (LSF), and mean absorbed dose was analyzed. Highly vascularized tumors translated into increased TNR. Treatment results (TNR and LSF) were significantly more variable for microspheres with high particle load. In our scenarios with 1.5 GBq perfusion, TNR was maximum for TheraSphere® at calibration time in segmentectomy/lobar technique, for SIR-Sphere® at 1-3 days post-calibration, and regarding QuiremSphere® at 3 days post-calibration. This novel approach is a decisive step towards developing a personalized dosimetry framework for TARE. MIDOS assists in making clinical decisions in TARE treatment planning by assessing various delivery parameters and simulating different tumor uptakes. MIDOS offers evaluation of treatment outcomes, such as TNR and LSF, and quantitative scenario-specific decisions.

Review on Microspheres: A Novel Approach in Drug Delivery System

A well-designed controlled drug delivery system has the potential to address the limitations of conventional drug therapy and enhance the therapeutic effectiveness of a drug. Microspheres, which are characterized by their particle size being 1-1000 μm, are considered a novel and controlled drug delivery system. The spherical shape of microspheres contributes to their advantageous properties. This review focuses on the utilization of microspheres as a novel drug delivery system. These characteristics can be modified by altering the materials, methods, polymers, or techniques used in the production of microspheres. Microspheres are composed of natural or synthetic polymers. They are utilized in drug delivery systems to achieve prolonged or controlled drug release, enhancing bioavailability, stability, and action at specific sites at predetermined rates. Microspheres can be manufactured using various natural or synthetic materials. Different types of microspheres include bio adhesive, magnetic, floating, radioactive, polymeric, biodegradable polymeric, and synthetic polymeric microspheres. These microspheres are prepared using methods such as spray drying, solvent evaporation, single emulsion technique, double emulsion technique, phase separation coacervation technique, spray drying and spray congealing, solvent extraction, and quasi-emulsion solvent diffusion. Microspheres have a wide range of applications and evaluation parameters. Keywords: Microsphere, Novel Drug Delivery, Types of Microspheres, Methods of preparation Microspheres, Biodegradable.

Dose finding study for unilobar radioembolization using holmium-166 microspheres to improve resectability in patients with HCC: the RALLY protocol

BackgroundHigh dose unilobar radioembolization (also termed ‘radiation lobectomy’)—the transarterial unilobar infusion of radioactive microspheres as a means of controlling tumour growth while concomitantly inducing future liver remnant hypertrophy—has recently gained interest as induction strategy for surgical resection. Prospective studies on the safety and efficacy of the unilobar radioembolization-surgery treatment algorithm are lacking. The RALLY study aims to assess the safety and toxicity profile of holmium-166 unilobar radioembolization in patients with hepatocellular carcinoma ineligible for surgery due to insufficiency of the future liver remnant.MethodsThe RALLY study is a multicenter, interventional, non-randomized, open-label, non-comparative safety study. Patients with hepatocellular carcinoma who are considered ineligible for surgery due to insufficiency of the future liver remnant (< 2.7%/min/m2 on hepatobiliary iminodiacetic acid scan will be included. A classical 3 + 3 dose escalation model will be used, enrolling three to six patients in each cohort. The primary objective is to determine the maximum tolerated treated non-tumourous liver-absorbed dose (cohorts of 50, 60, 70 and 80 Gy). Secondary objectives are to evaluate dose–response relationships, to establish the safety and feasibility of surgical resection following unilobar radioembolization, to assess quality of life, and to generate a biobank.DiscussionThis will be the first clinical study to assess the unilobar radioembolization-surgery treatment algorithm and may serve as a stepping stone towards its implementation in routine clinical practice.Trial registrationNetherlands Trial Register NL8902, registered on 2020–09-15.

Engineering Radioactive Microspheres for Intra‐Arterial Brachytherapy Using Radiation‐Induced Graft Polymerization

AbstractIntravascular brachytherapy requires advances in radio‐embolization technologies that combine brilliant radiostability efficacy with a facile and green synthesis route. A hybrid‐integrated radioactive microsphere strategy using phosphorylcholine‐modified lutetium‐177 coordinated polymeric microspheres (177Lu‐PCMs) is reported that are fabricated via radiation‐induced graft polymerization for imaging‐guided locoregional intravascular brachytherapy. The underlying formation mechanism of 177Lu‐PCMs is elucidated using first‐principles computations and density functional theory calculations, and 177Lu loading mechanisms are investigated with Near‐edge and extended X‐ray absorption fine structure spectroscopy. The engineered 177Lu‐PCMs exhibit excellent mechanical properties, good hydrophilicity, and controlled sphere diameter. These features provide advantages of ultra‐stable embolic radio‐theranostics, which is demonstrated in different preclinical rodent models and isolated human liver tumor tissues. During locoregional intra‐arterial brachytherapy, 177Lu‐PCMs can be visualized via SPECT to validate the in vivo biodistribution and retention in real time, achieving precise delivery, effective anti‐cancer treatment, and a distinguished safety profile without degradation, ectopic embolization, and adverse reactions. Therefore, this study offer a new avenue for the development of a highly innovative and translational approach for precision intra‐arterial brachytherapy.

Predictive value of 99mTc-MAA-based dosimetry in personalized 90Y-SIRT planning for liver malignancies

BackgroundSelective internal radiation therapy with 90Y radioembolization aims to selectively irradiate liver tumours by administering radioactive microspheres under the theragnostic assumption that the pre-therapy injection of 99mTc labelled macroaggregated albumin (99mTc-MAA) provides an estimation of the 90Y microspheres biodistribution, which is not always the case. Due to the growing interest in theragnostic dosimetry for personalized radionuclide therapy, a robust relationship between the delivered and pre-treatment radiation absorbed doses is required. In this work, we aim to investigate the predictive value of absorbed dose metrics calculated from 99mTc-MAA (simulation) compared to those obtained from 90Y post-therapy SPECT/CT.ResultsA total of 79 patients were analysed. Pre- and post-therapy 3D-voxel dosimetry was calculated on 99mTc-MAA and 90Y SPECT/CT, respectively, based on Local Deposition Method. Mean absorbed dose, tumour-to-normal ratio, and absorbed dose distribution in terms of dose-volume histogram (DVH) metrics were obtained and compared for each volume of interest (VOI). Mann–Whitney U-test and Pearson’s correlation coefficient were used to assess the correlation between both methods. The effect of the tumoral liver volume on the absorbed dose metrics was also investigated. Strong correlation was found between simulation and therapy mean absorbed doses for all VOIs, although simulation tended to overestimate tumour absorbed doses by 26%. DVH metrics showed good correlation too, but significant differences were found for several metrics, mostly on non-tumoral liver. It was observed that the tumoral liver volume does not significantly affect the differences between simulation and therapy absorbed dose metrics.ConclusionThis study supports the strong correlation between absorbed dose metrics from simulation and therapy dosimetry based on 90Y SPECT/CT, highlighting the predictive ability of 99mTc-MAA, not only in terms of mean absorbed dose but also of the dose distribution.

Super‐stable homogeneous embolic agents advance the treatment of hepatocellular carcinoma

Super‐stable homogeneous embolic agents advance the treatment of hepatocellular carcinoma

Safety of Radioembolization via the Cystic Artery in Patients with Hepatocellular Carcinoma and Parasitized Arterial Supply

PurposeTo evaluate the safety and effectiveness of radioembolization through the cystic artery supplying hepatocellular carcinoma (HCC) adjacent to the gallbladder. Materials and MethodsThis retrospective, single-center study included 24 patients who underwent radioembolization via the cystic artery between March 2017 and October 2022. The median tumor size was 8.3 cm (range, 3.4–20.4 cm). Twenty-two (92%) patients had Child-Pugh Class A disease, and 2 (8%) patients had Class B cirrhosis. Technical issues, adverse events, and tumor response were analyzed. ResultsInfusion of radioactive microspheres was performed from the main cystic artery (n = 6), the deep cystic artery (n = 9), and small feeders from the cystic artery (n = 9). The cystic artery supplied the primary index tumor in 21 patients. The median radiation activity delivered via the cystic artery was 0.19 GBq (range, 0.02–0.43 GBq). The median total radiation activity administered was 4.1 GBq (range, 0.9–10.8 GBq). There was no case of symptomatic cholecystitis requiring invasive intervention. One patient experienced abdominal pain during injection of radioactive microspheres via the cystic artery. Eleven (46%) patients received pain medication during or within 2 days of the procedure. Twelve (50%) patients had gallbladder wall thickening on a 1-month follow-up computed tomography scan. Based on follow-up imaging, 23 (96%) patients showed an objective response (complete or partial response) of the tumor supplied by the cystic artery. ConclusionRadioembolization via the cystic artery may be safe in patients with HCC partially supplied by the cystic artery.

Radioactive Microspheres for Selective Internal Radiation Therapy of Hepatocellular Carcinoma

Selective internal radiation therapy (SIRT) as one of the radiotherapeutic techniques has been widely used in the treatment of primary and metastatic liver cancer, for better avoiding radiation damage to normal tissues from external exposure. The radioactive microspheres used in SIRT should meet some special requirements closely associated with the type of radionuclides and the size and the property of the microsphere. This review focuses on the radioactive microspheres to elaborate the current challenges in the related fields, including simplification of the preparation of microspheres formed by different materials, visualization of the biodistribution of microspheres, and the suitability of different types of microspheres for repeated treatment. In this context, the major characteristics of three kinds of commercialized radioactive microspheres are compared, the advances in the radioactive microspheres achieved in recent years are summarized, and the future prospects of radioactive microspheres are discussed.

Polydopamine-Coated Radiolabeled Microspheres for Combinatorial Radioembolization and Photothermal Cancer Therapy.

Transarterial radioembolization (TARE) is a local radionuclide therapy and is successfully used in hepatocellular carcinoma (HCC) treatment. Radioactive microspheres have been widely studied for TARE. Preparation of ideal radioactive microspheres is significant for clinical research and patient treatment. In this study, we have designed a novel multifunctional microsphere, i.e., polydopamine (PDA)-coated 177Lu-radiolabeled silica microspheres (MS) denoted as 177Lu-MS@PDA, which can be used for TARE and photothermal therapy (PTT). The radiostability of 177Lu-MS@PDA was significantly improved by coating 177Lu-MS with PDA. In addition, the coating of PDA makes microspheres have excellent photothermal performance. MicroSPECT/CT images showed that 177Lu-MS@PDA was accurately embolized and remained in the tumor during the observation time. At the time, it also showed that 177Lu-MS@PDA was very stable in vivo. Furthermore, the anti-tumor results demonstrated that TARE combined with PTT of 177Lu-MS@PDA can significantly inhibit tumor growth without obvious side effects. 177Lu-MS@PDA holds great potential as a promising radioactive microsphere for HCC.

3D Hollow Porous Radio‐Granular Hydrogels for SPECT Imaging‐Guided Cancer Intravascular Brachytherapy

AbstractRadioactive microspheres have shown excellent therapeutic effects in the treatment of advanced hepatocellular carcinoma (HCC) due to indiscriminate embolization and killing of tumor cells. However, limitations such as unstable loading, in vivo reflux, and untrackable radioactive microspheres restrict their clinical applicability. Herein, a novel injectable lutetium‐177‐labeled 3D hollow porous radio‐granular hydrogels with a double‐cross‐linked network (177Lu‐3D‐HPGH) are synthesized via microfluidics combined with ultraviolet photo‐cross‐linking technology is reported. The radiolabeling efficiency of 177Lu‐3D‐HPGH can reach 97.85%. The 3D hollow porous radio‐granular hydrogels exhibited uniform, controllable size, radio‐theranostics, and excellent underwater adhesion properties, avoiding unwanted radiation damage to non‐target organs. Particularly, the extended X‐ray absorption fine structure combined with the density functional theory calculation revealed the mechanism of 3D‐HPGH loading with 177Lu through Lu‐N/O coordination. Furthermore, rabbit orthotopic kidney and liver tumor models are used to verify the excellent embolization performance, radionuclide loading stability, anti‐reflux characteristics, anti‐tumor effect, and biosafety of 177Lu‐3D‐HPGH. Briefly, this facile, green, and safe synthesis strategy provides a superior choice for intravascular brachytherapy of HCC and has great application value and transformative potential in clinical diagnosis and treatment.

Microsphere A Novel Drug Delivery System – A Review

The microspheres are also called as micro-particles. Microspheres are characteristically spherical &amp; free flowing powders having particle size ranging from 1-1000μm consisting of proteins or synthetic polymers. Microsphere can be manufactured by various type of material such as glass, polymers, and ceramic microspheres Microspheres are used in drug delivery systems to overcome some of the problems of conventional therapy and enhance the therapeutic efficacy of a given drug they are designed. These delivery systems offer numerous advantages compared to conventional dosage forms, which include improved efficacy, reduced toxicity, improved patient compliance and convenience. At the target tissue the drug should deliver in an optimal amount in the right period of time with the minimum side effect &amp; maximum therapeutic effect, to get the desired effect. The microspheres received much attention not only for the prolonged release or controlled drug delivery to improve bioavailability, stability and action at the specific site to predetermined rate but also for targeting of the anticancer drugs to the tumour. Microspheres are various types like Bioadhesive microspheres, Magnetic microspheres, Floating microspheres, radioactive microspheres, Polymeric microspheres, Biodegradable polymeric microspheres, Synthetic polymeric microspheres. The microsphere are spherical microparticles &amp; are used where predictable &amp; consistent particle surface area is important. The microspheres has the drug located centrally within the particle where it is encased within the unique polymeric membrane. This review focuses on types, materials used, drawbacks, advantage &amp; disadvantage.