Au@109Pd core-shell nanoparticle conjugated to trastuzumab for the therapy of HER2+ cancers: studies on the applicability of 109Pd/109mAg in vivo generator in combined ß- auger electron therapy.

BACKGROUND: In radionuclide therapy, to enhance therapeutic efficacy, an intriguing alternative is to ensure the simultaneous implementation of low- and high-LET radiation emitted from a one radionuclide. In the present study, we introduce the concept of utilizing 109Pd (T1/2 = 13.7 h) in the form of a 109Pd/109mAg in vivo generator. In this system, 109Pd emits beta particles of medium energy, while 109mAg releases a cascade of conversion and Auger electrons. 109Pd was utilized in the form of 15 nm gold nanoparticles, which were coated with a monolayer of 109Pd. In this system, the 109Pd atoms are on the surface of the nanoparticle, while the 109mAg atoms generated in the decay reaction possess the capability for unhindered emission of Auger electrons. RESULTS: 109Pd, obtained through neutron irradiation of natural palladium, was deposited onto 15-nm gold nanoparticles, exceeding a efficiency rate of 95%. In contrast to previously published data on in vivo generators based on chelators, where the daughter radionuclide diffuses away from the molecules, daughter radionuclide 109mAg remains on the surface of gold nanoparticles after the decay of 109Pd. To obtain a radiobioconjugate with an affinity for HER2 receptors, polyethylene glycol chains and the monoclonal antibody trastuzumab were attached to the Au@Pd nanoparticles. The synthesized bioconjugate contained an average of 9.5 trastuzumab molecules per one nanoparticle. In vitro cell studies indicated specific binding of the Au@109Pd-PEG-trastuzumab radiobioconjugate to the HER2 receptor on SKOV-3 cells, resulting in 90% internalization. Confocal images illustrated the accumulation of Au@109Pd-PEG-trastuzumab in the perinuclear area surrounding the cell nucleus. Despite the lack of nuclear localization, which is necessary to achieve an effective cytotoxic effect of Auger electrons, a substantial cytotoxic effect, significantly greater than that of pure ß- and pure Auger electron emitters was observed. We hypothesize that in the studied system, the cytotoxic effect of the Auger electrons could have also occurred through the damage to the cell's nuclear membrane by Auger electrons emitted from nanoparticles accumulated in the perinuclear area. CONCLUSION: The obtained results show that trastuzumab-functionalized 109Pd-labeled nanoparticles can be suitable for the application in combined ß--Auger electron targeted radionuclide therapy. Due to both components decay (ß- and conversion/Auger electrons), the 109Pd/109mAg in vivo generator presents unique potential in this field. Despite the lack of nuclear localization, which is highly required for efficient Auger electron therapy, an adequate cytotoxic effect was attained.

Improvement of the Effectiveness of HER2+ Cancer Therapy by Use of Doxorubicin and Trastuzumab Modified Radioactive Gold Nanoparticles.

In the present article, we describe a multimodal radiobioconjugate that contains a chemotherapeutic agent (doxorubicin, DOX), a ß-emitter (198Au), and a guiding vector (trastuzumab, Tmab) for targeted therapy of cancers overexpressing HER2 receptors. To achieve this goal, radioactive gold nanoparticles (198AuNPs) with a mean diameter of 30 nm were synthesized and coated with a poly(ethylene glycol) (PEG) linker conjugated to DOX and monoclonal antibody (Tmab) via peptide bond formation. In vitro experiments demonstrated a high affinity of the radiobioconjugate to HER2 receptors and cell internalization. Cytotoxicity experiments performed using the MTS assay showed a significant decrease in the viability of SKOV-3 cells. A synergistic cytotoxic effect due to the simultaneous presence of DOX and 198Au was revealed after 48 h of treatment with 2.5 MBq/mL. Flow cytometry analysis indicated that DOX-198AuNPs-Tmab mainly induced cell cycle arrest in the G2/M phase and late apoptosis. Dose-dependent additive and synergistic effects of the radiobioconjugate were also shown in spheroid models. Ex vivo biodistribution experiments were performed in SKOV-3 tumor-bearing mice, investigating different distributions of the 198AuNPs-DOX and DOX-198AuNPs-Tmab after intravenous (i.v.) and intratumoral (i.t.) administration. Finally, in vivo therapeutic efficacy studies on the same animal model demonstrated very promising results, as they showed a significant tumor growth arrest up to 28 days following a single intratumoral injection of 10 MBq. Therefore, the proposed multimodal radiobioconjugate shows great potential for the local treatment of HER2+ cancers.

Platinum nanoparticles labelled with iodine-125 for combined "chemo-Auger electron" therapy of hepatocellular carcinoma.

Convenient therapeutic protocols against hepatocellular carcinoma (HCC) exhibit low treatment effectiveness, especially in the context of long-term effects, which is primarily related to late diagnosis and high tumor heterogeneity. Current trends in medicine concern combined therapy to achieve new powerful tools against the most aggressive diseases. When designing modern, multimodal therapeutics, it is necessary to look for alternative routes of specific drug delivery to the cell, its selective (with respect to the tumor) activity and multidirectional action, enhancing the therapeutic effect. Targeting the physiology of the tumor makes it possible to take advantage of certain characteristic properties of the tumor that differentiate it from other cells. In the present paper we designed for the first time iodine-125 labeled platinum nanoparticles for combined "chemo-Auger electron" therapy of hepatocellular carcinoma. High selectivity achieved by targeting the tumor microenvironment of these cells was associated with effective radionuclide desorption in the presence of H2O2. The therapeutic effect was found to be correlated with cell damage at various molecular levels including DNA DSBs and was observed in a dose-dependent manner. A three-dimensional tumor spheroid revealed successful radioconjugate anticancer activity with a significant treatment response. A possible concept for clinical application after prior in vivo trials may be achieved via transarterial injection of micrometer range lipiodol emulsions with encapsulated 125I-NP. Ethiodized oil gives several advantages especially for HCC treatment; thus bearing in mind a suitable particle size for embolization, the obtained results highlight the exciting prospects for the development of PtNP-based combined therapy.

Doxorubicin- and Trastuzumab-Modified Gold Nanoparticles as Potential Multimodal Agents for Targeted Therapy of HER2+ Cancers.

Recently, targeted nanoparticles (NPs) have attracted much attention in cancer treatment due to their high potential as carriers for drug delivery. In this article, we present a novel bioconjugate (DOX-AuNPs-Tmab) consisting of gold nanoparticles (AuNPs, 30 nm) attached to chemotherapeutic agent doxorubicin (DOX) and a monoclonal antibody, trastuzumab (Tmab), which exhibited specific binding to HER2 receptors. The size and shape of synthesized AuNPs, as well as their surface modification, were analyzed by the TEM (transmission electron microscopy) and DLS (dynamic light scattering) methods. Biological studies were performed on the SKOV-3 cell line (HER2+) and showed high specificity of binding to the receptors and internalization capabilities, whereas MDA-MB-231 cells (HER2-) did not. Cytotoxicity experiments revealed a decrease in the metabolic activity of cancer cells and surface area reduction of spheroids treated with DOX-AuNPs-Tmab. The bioconjugate induced mainly cell cycle G2/M-phase arrest and late apoptosis. Our results suggest that DOX-AuNPs-Tmab has great potential for targeted therapy of HER2-positive tumors.

Multimodal Radiobioconjugates of Magnetic Nanoparticles Labeled with 44Sc and 47Sc for Theranostic Application.

This study was performed to synthesize multimodal radiopharmaceutical designed for the diagnosis and treatment of prostate cancer. To achieve this goal, superparamagnetic iron oxide (SPIO) nanoparticles were used as a platform for targeting molecule (PSMA-617) and for complexation of two scandium radionuclides, 44Sc for PET imaging and 47Sc for radionuclide therapy. TEM and XPS images showed that the Fe3O4 NPs have a uniform cubic shape and a size from 38 to 50 nm. The Fe3O4 core are surrounded by SiO2 and an organic layer. The saturation magnetization of the SPION core was 60 emu/g. However, coating the SPIONs with silica and polyglycerol reduces the magnetization significantly. The obtained bioconjugates were labeled with 44Sc and 47Sc, with a yield higher than 97%. The radiobioconjugate exhibited high affinity and cytotoxicity toward the human prostate cancer LNCaP (PSMA+) cell line, much higher than for PC-3 (PSMA-) cells. High cytotoxicity of the radiobioconjugate was confirmed by radiotoxicity studies on LNCaP 3D spheroids. In addition, the magnetic properties of the radiobioconjugate should allow for its use in guide drug delivery driven by magnetic field gradient.

198Au-Coated Superparamagnetic Iron Oxide Nanoparticles for Dual Magnetic Hyperthermia and Radionuclide Therapy of Hepatocellular Carcinoma.

This study was performed to synthesize a radiopharmaceutical designed for multimodal hepatocellular carcinoma (HCC) treatment involving radionuclide therapy and magnetic hyperthermia. To achieve this goal, the superparamagnetic iron oxide (magnetite) nanoparticles (SPIONs) were covered with a layer of radioactive gold (198Au) creating core-shell nanoparticles (SPION@Au). The synthesized SPION@Au nanoparticles exhibited superparamagnetic properties with a saturation magnetization of 50 emu/g, which is lower than reported for uncoated SPIONs (83 emu/g). Nevertheless, the SPION@Au core-shell nanoparticles showed a sufficiently high saturation magnetization value which allows them to reach a temperature of 43 °C at a magnetic field frequency of 386 kHz. The cytotoxic effect of nonradioactive and radioactive SPION@Au-polyethylene glycol (PEG) bioconjugates was carried out by treating HepG2 cells with various concentrations (1.25-100.00 µg/mL) of the compound and radioactivity in range of 1.25-20 MBq/mL. The moderate cytotoxic effect of nonradioactive SPION@Au-PEG bioconjugates on HepG2 was observed. The cytotoxic effect associated with the ß- radiation emitted by 198Au was much greater and already reaches a cell survival fraction below 8% for 2.5 MBq/mL of radioactivity after 72 h. Thus, the killing of HepG2 cells in HCC therapy should be possible due to the combination of the heat-generating properties of the SPION-198Au-PEG conjugates and the radiotoxicity of the radiation emitted by 198Au.

Oxidative Status as an Attribute for Selective Antitumor Activity of Platinum-Containing Nanoparticles against Hepatocellular Carcinoma.

Overcoming the limitations for efficient and selective drug delivery is one of the most challenging obstacles for newly designed anticancer agents. In this study, we present two types of platinum-based nanoparticles (NP), ultrasmall 2 nm PtNPs and core-shell 30 nm Au@Pt, which can be highly cytotoxic in an oxidative environment and remain biologically inactive in cells with lower oxidative status. Our research highlighted the differences in platinum nanoparticle-induced chemotoxicity and is the first study examining its mechanism as a substantial aspect of Au@Pt/PtNPs biological activity. Selectively induced oxidative stress was found to be a primary trigger of NPs' toxicity. Significant differences between Au@Pt and PtNPs were observed especially during 24 h treatment, due to successful intranuclear PtNPs location (~13% of internalized fraction). Reactive oxygen species (ROS)-level induced from both NPs types were similar, while reduction of reduced glutathione (GSH) intracellular content was stronger after treatment with PtNPs. Any biological activity was found in HER2+ breast cancer cells, which have only slightly increased oxidative status. Platinum-containing nanoparticles are an interesting tool for the improvement of selectivity in anticancer therapies against hepatocellular carcinoma (HCC). Due to intranuclear uptake, 2 nm PtNPs seems to be more promising for further research for HCC therapy.

Multifunctional Nanoparticles Based on Iron Oxide and Gold-198 Designed for Magnetic Hyperthermia and Radionuclide Therapy as a Potential Tool for Combined HER2-Positive Cancer Treatment.

Iron oxide nanoparticles are commonly used in many medical applications as they can be easily modified, have a high surface-to-volume ratio, and are biocompatible and biodegradable. This study was performed to synthesize nanoparticles designed for multimodal HER2-positive cancer treatment involving radionuclide therapy and magnetic hyperthermia. The magnetic core (Fe3O4) was coated with a gold-198 layer creating so-called core-shell nanoparticles. These were then further modified with a bifunctional PEG linker and monoclonal antibody to achieve the targeted therapy. Monoclonal antibody-trastuzumab was used to target specific breast and nipple HER2-positive cancer cells. The nanoparticles measured by transmission electron microscopy were as small as 9 nm. The bioconjugation of trastuzumab was confirmed by two separate methods: thermogravimetric analysis and iodine-131 labeling. Synthesized nanoparticles showed that they are good heat mediators in an alternating magnetic field and exhibit great specific binding and internalization capabilities towards the SKOV-3 (HER2 positive) cancer cell line. Radioactive nanoparticles also exhibit capabilities regarding spheroid degradation without and with the application of magnetic hyperthermia with a greater impact in the case of the latter. Designed radiobioconjugate shows great promise and has great potential for in vivo studies regarding magnetic hyperthermia and radionuclide combined therapy.

Cubosomal Lipid Formulation for Combination Cancer Treatment: Delivery of a Chemotherapeutic Agent and Complexed α-Particle Emitter 213Bi.

Here, we propose tailored lipid liquid-crystalline carriers (cubosomes), which incorporate an anticancer drug (doxorubicin) and complexed short-lived α-emitter (bismuth-213), as a strategy to obtain more effective action toward the cancer cells. Cubosomes were formulated with doxorubicin (DOX) and an amphiphilic ligand (DOTAGA-OA), which forms stable complexes with 213Bi radionuclide. The behavior of DOX incorporated into the carrier together with the chelating agent was investigated, and the drug liberation profile was determined. The experiments revealed that the presence of the DOTAGA-OA ligand affects the activity of DOX when they are incorporated into the same carrier. This unexpected influence was explained based on the results of release studies, which proved the contribution of electrostatics in molecular interactions between the positively charged DOX and negatively charged DOTAGA-OA in acidic and neutral solutions. A significant decrease in the viability of HeLa cancer cells was achieved using sequential cell exposure: first to the radiolabeled cubosomes containing 213Bi complex and next to DOX-doped cubosomes. Therefore, the sequential procedure for the delivery of both drugs encapsulated in cubosomes is suggested for further biological and in vivo studies.

Nanostructures as Radionuclide Carriers in Auger Electron Therapy.

The concept of nanoparticle-mediated radionuclide delivery in the cancer treatment has been widely discussed in the past decade. In particular, the use of inorganic and organic nanostructures in the development of radiopharmaceuticals enables the delivery of medically important radioisotopes for radionuclide therapy. In this review, we present the development of nanostructures for cancer therapy with Auger electron radionuclides. Following that, different types of nanoconstructs that can be used as carriers for Auger electron emitters, design principles, nanoparticle materials, and target vectors that overcame the main difficulties are described. In addition, systems in which high-Z element nanoparticles are used as radionuclide carriers, causing the emission of photoelectrons from the nanoparticle surface, are presented. Finally, future research opportunities in the field are discussed as well as issues that must be addressed before nanoparticle-based Auger electron radionuclide therapy can be transferred to clinical use.

Hybrid Radiobioconjugated Superparamagnetic Iron Oxide-Based Nanoparticles for Multimodal Cancer Therapy.

Superparamagnetic iron oxide nanoparticles (SPIONs) are widely used for biomedical applications for their outstanding properties such as facile functionalization and doping with different metals, high surface-to-volume ratio, superparamagnetism, and biocompatibility. This study was designed to synthesize and investigate multifunctional nanoparticle conjugate to act as both a magnetic agent, anticancer immunological drug, and radiopharmaceutic for anticancer therapy. The carrier, 166Ho doped iron oxide, was coated with an Au layer, creating core-shell nanoparticles ([166Ho] Fe3O4@Au. These nanoparticles were subsequently modified with monoclonal antibody trastuzumab (Tmab) to target HER2+ receptors. We describe the radiobioconjugate preparation involving doping of a radioactive agent and attachment of the organic linker and drug to the SPIONs' surface. The size of the SPIONs coated with an Au shell measured by transmission electron microscopy was about 15 nm. The bioconjugation of trastuzumab onto SPIONs was confirmed by thermogravimetric analysis, and the amount of two molecules per one nanoparticle was estimated with the use of radioiodinated [131I]Tmab. The synthesized bioconjugates showed that they are efficient heat mediators and also exhibit a cytotoxic effect toward SKOV-3 ovarian cancer cells expressing HER2 receptors. Prepared radiobioconjugates reveal the high potential for in vivo application of the proposed multimodal hybrid system, combined with magnetic hyperthermia and immunotherapy against cancer tissues.

Au@Pt Core-Shell Nanoparticle Bioconjugates for the Therapy of HER2+ Breast Cancer and Hepatocellular Carcinoma. Model Studies on the Applicability of 193mPt and 195mPt Radionuclides in Auger Electron Therapy.

193mPt and 195mPt radionuclides are therapeutically attractive Auger electron emitters with notably high Auger electron yield per decay. The present paper summarizes the first step of research on the applications of core-shell (Au@Pt) nanoparticles for electron Auger therapy of HER2+ (human epidermal growth factor receptor 2) breast cancer and hepatocellular carcinoma. Gold nanoparticles (30 nm) were synthesized covered with a platinum shell at high efficiency (>80%) and were further evaluated for in vitro studies such as binding affinity, internalization and cytotoxicity. To find the mechanism(s) responsible for platinum cytotoxicity in HepG2 cells, the platinum concentration in isolated cell nuclei and cytoplasm was determined using ICP-MS (inductively coupled plasma mass spectrometry). Lack of platinum in cell nuclei suggests that the cytotoxic effect is associated with the generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS). Studies carried out on the SKOV-3 cell line with the use of a synthesized targeting bioconjugate (Au@Pt-PEG-trastuzumab) revealed a high affinity of this preparation to HER2+ cells, its internalization, its placement in the perinuclear area and partial intranuclear location. The specific binding for HER2 negative cells, MDA-MB-231, was negligible and Au@Pt-PEG-trastuzumab did not enter these cells. The results obtained are promising and warrant future investigation of Auger electron therapy using 193mPt and 195mPt based radiopharmaceuticals.

Radiochemical separation of 224Ra from 232U and 228Th sources for 224Ra/212Pb/212Bi generator.

The application of diagnostic and therapeutic radionuclides in nuclear medicine has grown significantly and has translated into the increased interest in radionuclide generators and their development. 224Ra and its shorter-lived daughters, 212Pb and 212Bi, are very interesting radionuclides from Targeted Alpha Therapy point of view for treatment of small cancers or metastatic forms. The purpose of the present work was to develop a simple generator for rapid elution of carrier-free 224Ra from 232U or 228Th sources by radiochemical separation based on extraction chromatography with the utilization of a home-made material. The bis(2-ethylhexyl) hydrogen phosphate (HDEHP) extractant was immobilized on polytetrafluroethylene (PTFE) grains and its ability to selectively adsorb 232U and 228Th, with simultaneous high elution recovery of 224Ra, was checked over few years. The 224Ra was quantitatively eluted with small volume (3-5 mL) of 0.1 M HNO3 with low breakthrough (<0.005%) and was used for further milking of 212Bi and 212Pb from DOWEX 50WX12 by 0.75 M and 2.0 M HCl, respectively. The elaborated here methods allowed high recovery of 224Ra, 212Pb and 212Bi radionuclides and their application in radiolabeling of various biomolecules.

IAEA Activities on 67Cu, 186Re, 47Sc Theranostic Radionuclides and Radiopharmaceuticals.

Despite interesting properties, the use of 67Cu, 186Re and 47Sc theranostic radionuclides in preclinical studies and clinical trials is curtailed by their limited availability due to a lack of widely established production methods. An IAEA Coordinated Research Project (CRP) was initiated to identify important technical issues related to the production and quality control of these emerging radionuclides and related radiopharmaceuticals, based on the request from IAEA Member States. The international team worked on targetry, separation, quality control and radiopharmaceutical aspects of the radionuclides obtained from research reactors and cyclotrons leading to preparation of a standard recommendations for all Member States. The CRP was initiated in 2016 with fourteen participants from thirteen Member States from four continents. Extraordinary results on the production, quality control and preclinical evaluation of selected radionuclides were reported in this project that was finalized in 2020. The outcomes, outputs and results of this project achieved by participating Member States are described in this minireview.

Lipidic Cubic-Phase Nanoparticles (Cubosomes) Loaded with Doxorubicin and Labeled with 177Lu as a Potential Tool for Combined Chemo and Internal Radiotherapy for Cancers.

Lipid liquid-crystalline nanoparticles (cubosomes) were used for the first time as a dual-modality drug delivery system for internal radiotherapy combined with chemotherapy. Monoolein (GMO)-based cubosomes were prepared by loading the anticancer drug, doxorubicin and a commonly used radionuclide, low-energy beta (ß-)-emitter, 177Lu. The radionuclide was complexed with a long chain derivative of DOTAGA (DOTAGA-OA). The DOTAGA headgroup of the chelator was exposed to the aqueous channels of the cubosomes, while, concerning OA, the hydrophobic tail was embedded in the nonpolar region of the lipid bilayer matrix, placing the radioactive dopant in a stable manner inside the cubosome. The cubosomes containing doxorubicin and the radionuclide complex increased the cytotoxicity measured by the viability of the treated HeLa cells compared with the effect of single-drug cubosomes containing either the DOX DOTAGA-OA or DOTAGA-OA-177Lu complex. Multifunctional lipidic nanoparticles encapsulating the chemotherapeutic agent together with appropriately complexed (ß-) radionuclide are proposed as a potential strategy for effective local therapy of various cancers.

Trastuzumab Modified Barium Ferrite Magnetic Nanoparticles Labeled with Radium-223: A New Potential Radiobioconjugate for Alpha Radioimmunotherapy.

Barium ferrite nanoparticles (BaFeNPs) were investigated as vehicles for 223Ra radionuclide in targeted α-therapy. BaFe nanoparticles were labeled using a hydrothermal Ba2+ cations replacement by 223Ra with yield reaching 61.3 ± 1.8%. Radiolabeled nanoparticles were functionalized with 3-phosphonopropionic acid (CEPA) linker followed by covalent conjugation to trastuzumab (Herceptin®). Thermogravimetric analysis and radiometric method with the use of [131I]-labeled trastuzumab revealed that on average 19-21 molecules of trastuzumab are attached to the surface of one BaFe-CEPA nanoparticle. The hydrodynamic diameter of BaFe-CEPA-trastuzumab conjugate is 99.9 ± 3.0 nm in water and increases to 218.3 ± 3.7 nm in PBS buffer, and the zeta potential varies from +27.2 ± 0.7 mV in water to -8.8 ± 0.7 in PBS buffer. The [223Ra]BaFe-CEPA-trastuzumab radiobioconjugate almost quantitatively retained 223Ra (>98%) and about 96% of 211Bi and 94% of 211Pb over 30 days. The obtained radiobioconjugate exhibited high affinity, cell internalization and cytotoxicity towards the human ovarian adenocarcinoma SKOV-3 cells overexpressing HER2 receptor. Confocal studies indicated that [223Ra]BaFe-CEPA-trastuzumab was located in peri-nuclear space. High cytotoxicity of the [223Ra]BaFe-CEPA-trastuzumab bioconjugate was confirmed by radiotoxicity studies on SKOV-3 cell monolayers and 3D-spheroids. In addition, the magnetic properties of the radiobioconjugate should allow for its use in guide drug delivery driven by magnetic field gradient.

Design and Evaluation of 223Ra-Labeled and Anti-PSMA Targeted NaA Nanozeolites for Prostate Cancer Therapy-Part I.

Prostate cancer is the second most frequent malignancy in men worldwide. Unfortunately, current therapies often lead to the onset of metastatic castration-resistant prostate cancer (mCRPC), causing significant mortality. Therefore, there is an urgent need for new and targeted therapies that are advantageous over the current ones. Recently, the PSMA-targeted radioligand therapy of mCRPC has shown very promising results. In line with this, we described the synthesis of a new radioimmunoconjugate, 223RaA-silane-PEG-D2B, for targeted mCRPC therapy. The new compound consists of a NaA zeolite nanocarrier loaded with the α-particle emitting Ra-223 radionuclide, functionalized with the anti-PSMA D2B antibody. Physicochemical properties of the synthesized compound were characterized by standard methods (HR-SEM, TEM, XRD, FTIR, EDS, NTA, DLS, BET, TGA). The targeting selectivity, the extent of internalization, and cytotoxicity were determined in LNCaP C4-2 (PSMA+) and DU-145 (PSMA-) cells. Our results supported the 223RaA-silane-PEG-D2B synthesis and revealed that the final product had a diameter ca. 120 nm and specific activity 0.65 MBq/1mg. The product was characterized by a high yield of stability (>95% up to 12 days). The conjugation reaction resulted in approximately 50 antibodies/nanoparticle. The obtained radioimmunoconjugate bound specifically and internalized into PSMA-expressing LNCaP C4-2 cells, but not into PSMA-negative DU-145 cells. 223RaA-silane-PEG-D2B demonstrated also potent cytotoxicity in LNCaP C4-2 cells. These promising results require further in vivo evaluation of 223RaA-silane-PEG-D2B with regard to its toxicity and therapeutic efficacy.

Separation of Radionuclides from Spent Decontamination Fluids via Adsorption onto Titanium Dioxide Nanotubes after Photocatalytic Degradation.

A one-step process combining the photocatalytic degradation of radionuclide complexes and the adsorption of liberated radionuclides on titanium dioxide nanotubes was developed and tested for the purification of aqueous waste produced from chemical decontamination of nuclear power plant circuit components. Among the tested forms of TiO2, only nanotubes exhibit both high photocatalytic activity and sorption ability, which support their application in a one-step purification process. The obtained results indicate that the photocatalytic degradation of complexes followed by the sorption of the radionuclides onto TiO2 nanotubes offers a promising route for treating spent decontamination fluids.

Nanoparticles in Targeted Alpha Therapy.

Recent advances in the field of nanotechnology application in nuclear medicine offer the promise of better therapeutic options. In recent years, increasing efforts have been made on developing nanoconstructs that can be used as carriers for immobilising alpha (α)-emitters in targeted drug delivery. In this publication, we provide a comprehensive overview of available information on functional nanomaterials for targeted alpha therapy. The first section describes why nanoconstructs are used for the synthesis of α-emitting radiopharmaceuticals. Next, we present the synthesis and summarise the recent studies demonstrating therapeutic applications of α-emitting labelled radiobioconjugates in targeted therapy. Finally, future prospects and the emerging possibility of therapeutic application of radiolabelled nanomaterials are discussed.

Targeted Radionuclide Therapy of Prostate Cancer-From Basic Research to Clinical Perspectives.

Prostate cancer is the most commonly diagnosed malignancy in men and the second leading cause of cancer-related deaths in Western civilization. Although localized prostate cancer can be treated effectively in different ways, almost all patients progress to the incurable metastatic castration-resistant prostate cancer. Due to the significant mortality and morbidity rate associated with the progression of this disease, there is an urgent need for new and targeted treatments. In this review, we summarize the recent advances in research on identification of prostate tissue-specific antigens for targeted therapy, generation of highly specific and selective molecules targeting these antigens, availability of therapeutic radionuclides for widespread medical applications, and recent achievements in the development of new-generation small-molecule inhibitors and antibody-based strategies for targeted prostate cancer therapy with alpha-, beta-, and Auger electron-emitting radionuclides.