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Prostate-specific membrane antigen (PSMA), overexpressed in prostate cancer, has become a popular target for radionuclide-based theranostic applications in the advanced stages of prostate cancer. We conducted a meta-analysis of the therapeutic effects of PSMA-targeting α-therapy (

Thirty-eight patients with CRPC with progressive disease following at least one taxane-based chemotherapy receivedA composite response by predetermined criteria was observed in 25 (66%) of 38 patients. The median PFS was 8 months (95% CI 5.3-10.6 months). Median overall survival was 12 months (95% CI 9.1-14.9) with 16 patients alive at the time of censorship. There was no difference in response rates or survival statistics between patients with visceral metastases versus those with only bone and lymph-node metastases (Chi-square 1.51, df 1, Sig 0.218). The most common adverse effect was xerostomia. On the QOL Symptom score, Pain, Fatigue Insomnia, and constipation showed a significant improvement as compared to baseline.

Environmental radioactive materials are measured to determine background levels of radiation or to assess the level of contamination because of human activity. The study in this paper focuses on the determination of the natural radionuclide vector of soil in the area of A1 NPP in Jaslovske Bohunice, which is under the decommissioning process shutdown after the accident. To achieve this goal, soil samples were taken and evaluated by semiconductor HPGe gamma- ray spectrometry under laboratory conditions. Hard-to-measure radionuclides were calculated based on radioactive equilibrium. Radioactive equilibrium was confirmed by measuring samples that were in secular equilibrium. The mass activity of radionuclides from thorium, uranium, and actinium series was determined for gamma-ray photon energies higher than 50 keV with an intensity higher than 0.1 % to ensure all relevant contributions to the background gamma spectrum. Based on the obtained radionuclide vector, the background spectrum can be reconstructed by calculation in order to determine the background level for essentially any measurement geometry. The motivation for this study was to determine the background spectrum when measuring soil around A1 NPP for the purposes of future use of scanning measurement as a support in site characterization (characterization survey and final-status survey) during the decommissioning process.

Purpose of review Targeting Prostate-Specific Membrane Antigen (PSMA) has paved the way for personalized medicine in prostate cancer (PCa) patients. This review aims to highlight the role of PSMA targeting antibodies in PCa, for diagnostic and therapeutic purposes. Recent findings PSMA Positron Emission Tomography/Computed Tomography has been a game changer in the diagnosis of PCa in the recent decade. Two anti-PSMA monoclonal antibodies have been studied in PCa: 7E11-C35 (limited use) and J591. J591 antibody was used for diagnostic purposes coupled with different radionuclides. Most importantly, it was combined to numerous therapeutic radionuclides such as Lutetium-177 (177Lu), Yttrium-90 (90Y), Indium-111 (111In), and Actinium-225 (225Ac). It was also conjugated to drugs forming antibody-drug conjugates (e.g. MLN2704 and PSMA-ADC). These compounds were tested in recent phase I/II clinical trials. Summary PSMA targeting antibodies are very promising for further clinical investigation and continue to be a momentous research area, for both imaging and therapeutic settings. Although some clinical trials resulted in unfavorably safety profiles for some antibodies, they validated PSMA as a crucial immunoconjugate target.

The good efficacy of radioligand therapy (RLT) targeting prostate specific-membrane antigen (PSMA) for the treatment of metastatic castration-resistant prostate cancer (mCRPC) has been recently demonstrated in several clinical studies. However, the treatment effect of 177Lu-PSMA-ligands is still suboptimal for a significant fraction of patients. In contrast to external beam radiotherapy, the radiation dose distribution itself is strongly influenced by the heterogeneous tumour microenvironment. Although microdosimetry is critical for RLT treatment outcome, it is difficult to clinically or experimentally establish the quantitative relation. We propose an in silico approach to quantitatively investigate the microdosimetry and its influence on treatment outcome for PSMA-directed RLT of two different radioisotopes 177Lu and 225 Ac. The ultimate goal is optimize the combined 177 Lu and 225 Ac-PSMA therapy and maximize the anti-tumour effect, while minimizing irradiation of off-target tissues.Clinical relevance- With the proposed hybrid model we show that 177Lu-PSMA-ligands treatment assures a more homogeneously distributed dose and a lower dependency of the treatment outcome on the domain vascularisation. On the other hand, the 225Ac-PSMA-ligands treatment shows a much stronger efficacy in killing tumor cells with an equivalent mean dose distribution even in an hypoxic environment.

Hepatocellular carcinoma is the most common primary liver cancer and the fifth most frequently diagnosed cancer worldwide. Most patients with advanced disease are offered non-surgical palliative treatment options. This work explores the first α-emitting radioembolization for the treatment and monitoring of hepatic tumors. Furthermore, this works demonstrates the first in vivo simultaneous multiple-radionuclide SPECT images of the complex decay chain of an [225Ac]Ac-labeled agent using a clinical SPECT system to monitor the temporal distribution. Methods: A DOTA chelator was modified with a lipophilic moiety and radiolabeled with Actinium-225. The resulting agent, [225Ac]Ac-DOTA-TDA, was emulsified in Lipiodol® and evaluated in vivo in mouse model and the VX2 rabbit technical model of liver cancer. SPECT imaging was performed to monitor distribution of the TAT agent and the free daughters.Results: [225Ac]Ac-DOTA-TDA was shown to retain within the HEP2G tumors and VX2 tumor, with minimal uptake within normal tissue. In the mouse model, significant improvements in overall survival were observed. SPECT imaging was able to distinguish between the Actinium-225 agent (Francium-221) and the loss of the longer lived daughter, Bismuth-213. Conclusion: A TAT agent emulsified in Lipiodol® is capable of targeting liver tumors with minimal accumulation in normal tissue, providing a potential therapeutic agent for the treatment of HCC as well as a variety of hepatic tumors. In addition, SPECT imaging presented here provides a foundation for imaging methodology and protocols that can be rapidly translated into the clinic to monitor Actinium-225-labeled agents.

Targeted radionuclide therapy with Actinium-225-labeled prostate-specific membrane antigen ligands (This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Searches were made using relevant keywords in the PubMed, Embase, and Scopus databases, and articles up to December 2020 were included. Data on efficacy and toxicity were extracted from the individual articles. Random-effects model was used for generating pooled estimates through meta-analysis.Ten articles comprising 256 patients were included. Overall, 62.8% (95% confidence interval, CI: 53.4-71.7%) of the patients treated with

Glypican-3 (GPC3) is expressed in 75% of hepatocellular carcinoma (HCC), but not normal liver, making it a promising HCC therapeutic target. GC33 is a full-length humanized monoclonal IgG1 specific to GPC3 that can localize to HCC in vivo. GC33 alone failed to demonstrate therapeutic efficacy when evaluated in patients with HCC, however, we posit that cytotoxic functionalization of the antibody with therapeutic radionuclides, may be warranted. Alpha particles, which are emitted by radioisotopes such as Actinium-225 (Ac-225) exhibit high linear energy transfer and short pathlength that, when targeted to tumors, can effectively kill cancer and limit bystander cytotoxicity. Macropa, an 18-member heterocyclic crown ether, can stably chelate Ac-225 at room temperature. Here, we synthesized and evaluated the efficacy of [225Ac]Ac&ndash, Macropa&ndash, GC33 in mice engrafted with the GPC3-expressing human liver cancer cell line HepG2. Following a pilot dose-finding study, mice (n = 10 per group) were treated with (1) PBS, (2) mass-equivalent unmodified GC33, (3) 18.5 kBq [225Ac]Ac&ndash, IgG1 (isotype control), (4) 9.25 kBq [225Ac]Ac&ndash, GC33, and (5) 18.5 kBq [225Ac]Ac&ndash, GC33. While significant toxicity was observed in all groups receiving radioconjugates, the 9.25 kBq [225Ac]Ac&ndash, GC33 group demonstrated a modest survival advantage compared to PBS (p = 0.0012) and 18.5 kBq [225Ac]Ac&ndash, IgG1 (p = 0.0412). Hematological analysis demonstrated a marked, rapid reduction in white blood cells in all radioconjugate-treated groups compared to the PBS and unmodified GC33 control groups. Our studies highlight a significant disadvantage of using directly-labeled biomolecules with long blood circulation times for TAT. Strategies to mitigate such treatment toxicity include dose fractionation, pretargeting, and using smaller targeting ligands.

The utility of β-emitter 177Lu-DOTATATE in patients of neuroendocrine tumors (NETs) with widespread skeletal metastases is limited by its relatively modest response rates and a significant concern for hematotoxicity. In such situations, targeted α therapy with 225Ac-DOTATATE can be potentially beneficial. In this report, a 46-year-old man with rectal NET and extensive skeletal metastases was treated upfront with 6 cycles of 225Ac-DOTATATE at 8 weeks' intervals. The patient showed excellent symptomatic, biochemical, and radiological response with no grade 3/4 adverse events. The first-line use of 225Ac-DOTATATE, therefore, presents a novel strategy for metastatic NETs with high skeletal disease burden.

The synthesis ofPSMA-617, DOTATATE were radiolabelled withA detailed chemistry study was presented for the synthesis of

[spa] El citoesqueleto de actina es un componente esencial de las células eucariotas que tiene un importante papel en muchas funciones biológicas básicas como el mantenimiento de la morfología, la migración, el tráfico intracelular, la adhesión, la división celular y la migración nuclear intercinética (INM) entre otros. Durante todos estos procesos, la actividad del citoesqueleto de actina está regulada por muchas proteínas conocidas como proteínas unidoras de actina (ABPs). En el tubo neural en desarrollo, los progenitores neurales presentan una polaridad apicobasal y una morfología alargada. El citoesqueleto de actina de estas células se ancla a la membrana apical, a través de las uniones adherentes mediadas por las N-cadherina y a la membrana basal, a través de las adhesiones focales mediadas por integrinas. Los núcleos de estos progenitores neurales adquieren diferentes posiciones a lo largo del eje apicobasal en función de la fase del ciclo en la que se encuentran gracias a un proceso conocido como migración nuclear intercinética (INM), que proporciona al tejido su apariencia pseudoestratificada. En la presente tesis hemos identificado proteínas unidoras de actina (ABPs) como la α-actinina4, la α-E-catenina, la α-N-catenina, la cortactina, la Dbnl y la vinculina, que se unen a la N-cadherina a través de su dominio de unión a la β-Catenina en el tubo neural de pollo. Nuestro trabajo se centra en la función de la vinculina durante el desarrollo de este neuroepitelio donde hemos observado que esta ABP se localiza mayoritariamente en las membranas apical y basal del tubo neural. La vinculina es una proteína esencial para la correcta distribución de actina a lo largo del eje apicobasal y para el mantenimiento de la morfología tisular del tubo neural. Además, en nuestro trabajo demostramos que el citoesqueleto de actina y la vinculina participan en la regulación de la INM, especialmente en la migración apical, y en la correcta progresión del ciclo celular de los progenitores neurales del tubo neural de pollo a través de su unión a las moléculas de adhesión.

Interest in the use of

The LaBr3(Ce) detector has attracted much attention in recent years because of its superior characteristics compared with other scintillating materials in terms of resolution and efficiency. However, it has a relatively high intrinsic background radiation because of the naturally occurring radioisotopes in lanthanum, actinium, and their daughter nuclei. This limits its applications in low-counting rate experiments. In this study, we identified the radioactive isotopes in the $$\phi 3''\times 3''$$ Saint-Gobain B380 detector by a coincidence measurement using a Clover detector in a low-background shielding system. Moreover, we carried out a Geant4 simulation of the experimental spectra to evaluate the activities of the main internal radiation components. The total activity of the background radiation of B380 is determined to be 1.523 (34) Bq/cm3. The main sources include 138La at 1.428 (34) Bq/cm3, 207Tl at 0.0135 (13) Bq/cm3, 211Bi at 0.0136 (15) Bq/cm3, 215Po at 0.0135 (3) Bq/cm3, 219Rn at 0.0125 (12) Bq/cm3, 223Fr at 0.0019 (11) Bq/cm3, 223Ra at 0.0127 (10) Bq/cm3, 227Th at 0.0158 (22) Bq/cm3, and 227Ac at 0.0135 (13) Bq/cm3. Of these, the activities of 207Tl, 211Po, 215Po, 223Fr, and 227Ac are deduced for the first time from the secular equilibrium established in the decay chain of 227Ac.

We performed Monte Carlo simulations in order to determine, by means of microdosimetry calculations, tumour control probability (TCP) curves for treatments with

Targeted alpha-radiation therapy (TAT) withObservational cohort study including consecutive patients treated withThirteen patients were included. Median OS was 8.5 months for the total cohort and 12.6 months for PSMA radioligand therapy-naïve patients. PSA declines of ≥90% and ≥50% were observed in 46% and 69% of patients, respectively. Six patients were radiologically evaluable; 50% showed partial response. All patients showed90% total tumor volume reduction on PET imaging. Patients experienced clinically relevant decrease of pain and QoL improvement in physical and role functioning domains. Xerostomia persisted during follow-up. Patients with high baseline immunohistochemical PSMA expression or DNA damage repair alterations tended to have longer OS.TAT with

Targeted alpha-therapy (TAT) has great potential for treating a broad range of late-stage cancers by delivering a focused and lethal radiation dose to tumors. Actinium-225 (

Treatment of advanced metastatic castration-resistant prostate cancer after failure of approved therapy options remains challenging. Prostate-specific membrane antigen (PSMA)-targeting β- and α-emitters have been introduced, with promising response rates. Here, we present the first-to our knowledge-clinical data for PSMA-targeted α-therapy (TAT) using

Rationale: Despite the success of several standards of care treatment options in metastatic castration-resistant prostate cancer (mCRPC), a significant number of patients attain therapeutic resistance and eventually develop disease progression. Managing these patients are currently challenging. Hence, there is an unmet need for further efficient therapeutic options that induce anti-tumor activity and improve survival. The objective of this study was to assess the safety and therapeutic efficacy of 225Ac-PSMA-617 targeted alpha therapy (TAT) in mCRPC patients in real-world conditions. Methods: In this prospective study, we recruited patients with mCRPC who either were refractory to 177Lu-PSMA-617 radioligand therapy (RLT) or did not receive previous 177Lu-PSMA-617 RLT. Patients were treated with 225Ac-PSMA-617 TAT (100 KBq/Kg body weight) at 8-weekly intervals. The primary endpoint included the assessment of biochemical response by measuring the serum prostate-specific antigen (PSA) response rate as per the prostate cancer working group criteria (PCWG3). Secondary endpoints comprised the estimation of overall survival (OS), progression-free survival (PFS), molecular tumor response assessment (PERCIST 1 criteria), disease control rate (DCR), toxicity according to CTCAE v5.0, and clinical response evaluation. Results: A total of 28 patients were recruited for this cohort study among whom 15 (54%) received prior 177Lu-PSMA-617 RLT and the remaining 13 (46%) patients were 177Lu-PSMA-617 RLT naïve. The mean age was 69.7 years (range: 46-87 years). All patients, except one, had extensive skeletal metastases on baseline 68Ga-PSMA-11 PET/CT scan; one patient had lymph node dominant disease and advanced primary prostatic tumor. The mean activity administered was 26.5 ± 12 MBq (range: 9.25 - 62.9 MBq) [715.5 ± 327 µCi, range: 250 - 1700 µCi] with a median of 3 cycles (range: 1 - 7 cycles). At 8th week of post first cycle of 225Ac-PSMA-617 therapy (initial follow-up) and the end of the follow-up, >50% decline in PSA was observed in 25% and 39%, respectively. The median PFS and OS were 12 months (95% CI: 9 - 13 months) and 17 months (95% CI: 16 months - upper limit not reached), respectively. Molecular tumor response by PERCIST 1 criteria could be conducted in 22/28 (78.6%) patients, which revealed complete response in 2/22 (9%), partial response in 10/22 (45.4%) patients, 2/22 (9%) with stable disease, and 8/22 (36%) with progressive diseases. The disease control rate, according to the biochemical and molecular tumor response criteria, was 82% and 63.6%, respectively. Multivariate analysis revealed PSA progression as adverse prognostic indicator of OS, and any PSA decline as a good prognostic indicator of PFS. There was no Grade III/IV toxicity noted in this series. The most common side-effect was transient fatigue (50%) followed by grade I/II xerostomia (29%). Conclusion: 225Ac-PSMA-617 TAT showed promising disease control rate, even when all other therapeutic options were exhausted, with low treatment-related toxicities.

Very late antigen 4 (VLA-4; also called integrin α4β1) is overexpressed in melanoma tumor cells with an active role in tumor growth, angiogenesis, and metastasis, making VLA-4 a potential target for targeted alpha therapy (TAT).An anti-VLA-4 antibody was conjugated to DOTA for [[The work presented here demonstrated that [

PSMA-based radioligand therapies have shown the beneficial effect in metastatic castrate-resistant prostate cancer (mCRPC) patients when they become refectory to the established treatments with associated potential toxicities and high mortality rate. Ac-PSMA therapy is known to be remarkably effective in substantially pretreated mCRPC patients. However, posttherapy imaging is usually not performed as alpha emitters are really difficult to image. We presents a patient of mCRPC treated with Ac-PSMA-617, and his posttherapy whole-body scans acquired by using 3 different photopeaks (78, 218, and 440 keV) fairly demonstrated the tracer's distribution and the efficacy of targeted alpha therapy.

Prostate-specific membrane antigen (PSMA)-targeted radionuclide therapy (RNT) may increase tumor immunogenicity. We aimed at exploiting this effect by combining RNT with immunotherapy in a mouse model of prostate cancer (PC).

The alpha-emitter

Advances in targeted α-therapies have increased the interest in actinium (Ac), whose chemistry is poorly defined due to scarcity and radiological hazards. Challenges associated with characterizing Ac3+ chemistry are magnified by its 5f06d0 electronic configuration, which precludes the use of many spectroscopic methods amenable to small amounts of material and low concentrations (like EPR, UV-vis, fluorescence). In terms of nuclear spectroscopy, many actinium isotopes (225Ac and 227Ac) are equally "unfriendly" because the actinium α-, β-, and γ-emissions are difficult to resolve from the actinium daughters. To address these issues, we developed a method for isolating an actinium isotope (228Ac) whose nuclear properties are well-suited for γ-spectroscopy. This four-step procedure isolates 228Ra from naturally occurring 232Th. The relatively long-lived 228Ra (t1/2 = 5.75(3) years) radioisotope subsequently decays to 228Ac. Because the 228Ac decay rate [t1/2 = 6.15(2) h] is fast, 228Ac rapidly regenerates after being harvested from the 228Ra parent. The resulting 228Ac generator provides frequent and long-term access (of many years) to the spectroscopically "friendly" 228Ac radionuclide. We have demonstrated that the 228Ac product can be routinely "milked" from this generator on a daily basis, in chemically pure form, with high specific activity and in excellent yield (∼95%). Hence, in the same way that developing synthesis routes to new starting materials has advanced coordination chemistry for many metals by broadening access, this 228Ac generator has the potential to broaden actinium access for the inorganic community, facilitating the characterization of actinium chemical behavior.

Radioimmunotherapy, an approach using radiolabeled antibodies, has had minimal success in the clinic with several β-emitting radionuclides for the treatment of ovarian cancer. Alternatively, radioimmunotherapy with α-emitters offers the advantage of depositing much higher energy over shorter distances but was thought to be inappropriate for the treatment of solid tumors, for which antibody penetration is limited to a few cell diameters around the vascular system. However, the deposition of high-energy α-emitters to tumor markers adjacent to a typical leaky tumor vascular system may have large antitumor effects at the tumor vascular level, and their reduced penetration in normal tissue would be expected to lower off-target toxicity. Methods: To evaluate this concept, DOTAylated-huCC49 was labeled with the α-emitter (225)Ac to target tumor-associated glycoprotein 72–positive xenografts in a murine model of ovarian cancer. Results: (225)Ac-labeled DOTAylated-huCC49 radioimmunotherapy significantly reduced tumor growth in a dose-dependent manner (1.85, 3.7, and 7.4 kBq), with the 7.4-kBq dose extending survival by more than 3-fold compared with the untreated control. Additionally, a multitreatment regime (1.85 kBq followed by 5 weekly doses of 0.70 kBq for a total of 5.4 kBq) extended survival almost 3-fold compared with the untreated control group, without significant off-target toxicity. Conclusion: These results establish the potential for antibody-targeted α-radionuclide therapy for ovarian cancer, which may be generalized to α-radioimmunotherapy in other solid tumors.

It has been proven and confirmed in numerous repeated tests, that the use of a combination of several therapeutic methods gives much better treatment results than in the case of separate therapies. Particularly promising is the combination of ionizing radiation and magnetic hyperthermia in one drug. To achieve this objective, magnetite nanoparticles have been modified in their core with α emitter 225Ac, in an amount affecting only slightly their magnetic properties. By 3-phosphonopropionic acid (CEPA) linker nanoparticles were conjugated covalently with trastuzumab (Herceptin®), a monoclonal antibody that recognizes ovarian and breast cancer cells overexpressing the HER2 receptors. The synthesized bioconjugates were characterized by transmission electron microscopy (TEM), Dynamic Light Scattering (DLS) measurement, thermogravimetric analysis (TGA) and application of 131I-labeled trastuzumab for quantification of the bound biomolecule. The obtained results show that one 225Ac@Fe3O4-CEPA-trastuzumab bioconjugate contains an average of 8–11 molecules of trastuzumab. The labeled nanoparticles almost quantitatively retain 225Ac (>98%) in phosphate-buffered saline (PBS) and physiological salt, and more than 90% of 221Fr and 213Bi over 10 days. In human serum after 10 days, the fraction of 225Ac released from 225Ac@Fe3O4 was still less than 2%, but the retention of 221Fr and 213Bi decreased to 70%. The synthesized 225Ac@Fe3O4-CEPA-trastuzumab bioconjugates have shown a high cytotoxic effect toward SKOV-3 ovarian cancer cells expressing HER2 receptor in-vitro. The in-vivo studies indicate that this bioconjugate exhibits properties suitable for the treatment of cancer cells by intratumoral or post-resection injection. The intravenous injection of the 225Ac@Fe3O4-CEPA-trastuzumab radiobioconjugate is excluded due to its high accumulation in the liver, lungs and spleen. Additionally, the high value of a specific absorption rate (SAR) allows its use in a new very perspective combination of α radionuclide therapy with magnetic hyperthermia.

We present here a case with β-radiation-refractory metastatic neuroendocrine tumors, who demonstrated an excellent therapy response after 1 cycle of Ac-DOTATOC, without any significant adverse effects even after 10 cycles of β-emitter peptide receptor radionuclide therapy followed by α-peptide receptor radionuclide therapy.

²²⁵Ac-PSMA-617 targeted-therapy has demonstrated efficacy in 75-85% of patients; however, responses are not durable. We aimed to establish translatable mouse models of disseminated prostate cancer (PCa) to evaluate effectiveness of ²²⁵Ac-PSMA-617 at various disease stages. Methods: C4-2, C4-2B, or 22Rv1 cells were injected into the left ventricle of male NSG mice. Disease progression was monitored using bioluminescence imaging (BLI). For treatment, mice were injected with 40 kBq ²²⁵Ac-PSMA-617 at one (early treatment cohort) or three weeks (late treatment cohort) post-inoculation. Treatment efficacy was monitored by BLI of whole-body tumor burden. Mice were sacrificed based on body conditioning score. Results: C4-2 cells yielded metastases in liver, lungs, spleen, stomach, bones, and brain - achieving a clinically relevant model of widespread metastatic disease. The disease burden in the early treatment cohort was stable over 27 weeks in 5/9 mice and progressive in 4/9 mice. These mice were sacrificed due to brain metastases. Median survival of the late treatment cohort was superior to controls (13 vs. 7 weeks; p

Hu11B6 is a monoclonal antibody that internalizes in cells expressing androgen receptor (AR)-regulated prostate-specific enzyme human kallikrein-related peptidase 2 (hK2; KLK2 ). In multiple rodent models, Actinium-225–labeled hu11B6-IgG 1 ([ 225 Ac]hu11B6-IgG 1 ) has shown promising treatment efficacy. In the present study, we investigated options to enhance and optimize [ 225 Ac]hu11B6 treatment. First, we evaluated the possibility of exploiting IgG 3 , the IgG subclass with superior activation of complement and ability to mediate FC-γ-receptor binding, for immunotherapeutically enhanced hK2 targeted α-radioimmunotherapy. Second, we compared the therapeutic efficacy of a single high activity vs. fractionated activity. Finally, we used RNA sequencing to analyze the genomic signatures of prostate cancer that progressed after targeted α-therapy. [ 225 Ac]hu11B6-IgG 3 was a functionally enhanced alternative to [ 225 Ac]hu11B6-IgG 1 but offered no improvement of therapeutic efficacy. Progression-free survival was slightly increased with a single high activity compared to fractionated activity. Tumor-free animals succumbing after treatment revealed no evidence of treatment-associated toxicity. In addition to up-regulation of canonical aggressive prostate cancer genes, such as MMP7 , ETV1 , NTS , and SCHLAP1 , we also noted a significant decrease in both KLK3 (prostate-specific antigen ) and FOLH1 (prostate-specific membrane antigen) but not in AR and KLK2 , demonstrating efficacy of sequential [ 225 Ac]hu11B6 in a mouse model.

A decommissioning of nuclear fuel cycle facilities is inseparable from the problems of radioactive waste disposal. One of these problems is the categorization of a waste according to the content of beta- and alpha-emitters. Beta-emitters can be identified by existing technologies; however, the trouble arises when detecting alpha-emitting elements, primarily the long-lived members of the actinium chain with the specific activity of kBq/kg when they are spread inside a structural material. The report considers an application of an active neutron method-a differential die-away technology for reliable control of small quantities of FM. The essence of this method consists in sounding the interrogated item by pulsed thermal neutrons and recording the induced fission neutrons. The ratio of the number of fission neutrons to the number of source neutrons gives the normalized number of fission neutrons that is linked to the FM mass in the interrogated object. The work presents the scheme and principle of operation of an experimental device, as well as the results of measurement of concrete structures that contain internal traces of fissile materials. Analysis of the results shows that the proposed method allows the detection of ~ 6 mg of fissile material per kg of concrete with possible localization (cartogram) of the contaminated area.

Two lowest-energy odd-parity atomic levels of actinium, 7s27pP21/2o, 7s27pP23/2o, were observed via two-step resonant laser-ionization spectroscopy and their respective energies were measured to be 7477.36(4) and 12 276.59(2) cm-1. The lifetimes of these states were determined as 668(11) and 255(7) ns, respectively. In addition, we observed the effect of the hyperfine structure on the line for the transition to P23/2o. These properties were calculated using a hybrid approach that combines configuration interaction and coupled-cluster methods, in good agreement with the experiment. The data are of relevance for understanding the complex atomic spectra of actinides and for developing efficient laser cooling and ionization schemes for actinium, with possible applications for high-purity medical-isotope production and future fundamental physics experiments. © 2020 American Physical Society. The authors thank V. V. Flambaum and V. A. Dzuba for stimulating discussions and providing the corrected lifetimes, and M. Block, Ch. Mokry, and J. Runke for providing the actinium sample. We gratefully acknowledge discussions with R. Beerwerth and S. Fritzsche on the theory of the actinium hyperfine structure. The work was supported by the German Federal Ministry of Education and Research under the Projects No. 05P15UMCIA, No. 05P18UMCIA. D. B. was supported in part by the DFG Project ID 390831469: EXC 2118 (). D. B. also received support from the European Research Council (ERC) under the European Union Horizon 2020 Research and Innovation Program (Grant Agreement No. 695405), from the DFG Reinhart Koselleck Project. Theory work was supported in part by U.S. NSF Grant No. PHY-1620687. S. G. P. and M. G. K. acknowledge support by the Russian Science Foundation under Grant No. 19-12-00157.