Manual on the proper use of the 211At-labeled PSMA ligand ([211At]PSMA-5) for clinical trials of targeted alpha therapy (1st edition)

The version of record of this article, first published in Annals of Nuclear Medicine, is available online at Publisher’s website: https://doi.org/10.1007/s12149-024-01916-6.Recently, an astatine-labeled prostate-specific membrane antigen (PSMA) ligand ([211At]PSMA-5) has been developed for the targeted alpha therapy of patients with prostate cancer. This manual delineates its physicochemical characteristics to assist healthcare professionals in understanding the α-ray-emitting drug of [211At]PSMA-5 when administered to patients. The safety considerations regarding the handling and use of this drug in clinical trials are outlined, based on the proper usage manual of previous studies. The dose limits, as defined by the guidelines of the International Commission on Radiological Protection (ICRP) and the International Atomic Energy Agency (IAEA), are assessed for patients’ caregivers and the general public. According to the calculations provided in this manual, clinical trials involving [211At]PSMA-5 can be safely conducted for these populations even if patients are released after its administration. Moreover, this manual provides comprehensive guidance on the handling of [211At]PSMA-5 for healthcare facilities, and compiles a list of precautionary measures to be distributed among patients and their caregivers. While this manual was created by a research team supported by Ministry of Health, Labour, and Welfare in Japan and approved by Japanese Society of Nuclear Medicine, its applicability extends to healthcare providers in other countries. This manual aims to facilitate conducting clinical trials using [211At]PSMA-5 in patients with prostate cancer

エリンギ(Pleurotus eryngii)のトレハラーゼ : 酵素の分布、精製および性質について

Trehalase activity in a homogenized preparation from the fruit body of king oyster mushroom (eryngii), Pleurotus eryngii was studied in detail. Distribution of trehalose and trehalase activity was higher in the cap (pileus) fraction than in the other positions such as stalk (stipe). The tretalase peak 1 was purified by the Sephacryl S-200 and Toyopearl HW-55 column chromatography. Electorophoretic analysis of trehalase gave values of molecular weight of 36~37kDa, and oligomeric forms and blycoprotein forms of trehalase were suggested by the band patterns of resulting gels. Optimum conditons of pH and temperature were determined to be pH5.0 and 30℃, respectively. Trehalase peak 1 showed higher reactivity to α-, α-trehalose, whereas peak 2 enzyme showed higher activity to β-,β-trehalose, methyl-β-glucoside, and cellobiose, indicating that this enzyme might have a substrate specificity such asβ-glucosidase

Basic evaluation of the Eu:BaFBr and Ce:CaF2 hybrid type optical fiber based dosimeter system for correction of quenching effect under carbon ion irradiation

We fabricated the hybrid type optical fiber based dosimeter system using Eu:BaFBr and Ce:CaF2 optically stimulated luminescence (OSL) materials in order to correct the quenching effect under high LET particle irradiation. The fabricated dosimeter probe can obtain signals from both OSL materials through one optical fiber. We investigated the probe response by irradiating it with mono-energetic carbon ions and broad-spectrum ones making the spread-out Bragg peak (SOBP). We demonstrated that the SOBP shape can be improved by correction of the quenching effect using the relationship between the luminescence efficiency and the signal intensity ratio of both OSL materials

Manual on the proper use of meta-[211At] astato-benzylguanidine ([211At] MABG) injections in clinical trials for targeted alpha therapy

In this manuscript, we present the guideline for use of meta-[211At] astatobenzylguanidine ([211At] MABG), a newly introduced alpha emitting radiopharmaceutical to the up-coming World’s frst clinical trial for targeted alpha therapy (TAT) at Fukushima Medical University in Japan, focusing on radiation safety issues in Japan. This guideline was prepared based on a study supported by the Ministry of Health, Labour, and Welfare, and approved by the Japanese Society of Nuclear Medicine on Oct. 5th, 2021. The study showed that patients receiving [211At] MABG do not need to be admitted to a radiotherapy room and that TAT using [211At] MABG is possible on an outpatient basis. The radiation exposure from the patient is within the safety standards of the ICRP and IAEA recommendations for the general public and caregivers or patient’s family members. In this guideline, the following contents are also included: precautions for patients and their families, safety management associated with the use of [211At] MABG, education and training, and disposal of medical radioactive contaminants. TAT using [211At] MABG in Japan should be carried out according to this guideline. Although this guideline is based on the medical environment and laws and regulations in Japan, the issues for radiation protection and evaluation methodology presented in this guideline are useful and internationally acceptable as well

Particle dependence of quenching effect in an optical-fiber-type optically stimulated luminescence dosimeter

To monitor an actual dose in a patient’s body during radiotherapy treatment, we have developed a small-size dosimeter of an optical fiber probe mounting optically stimulated luminescence (OSL) materials at the tip. The OSL materials show a quenching effect when they are irradiated by charged particles with high linear energy transfer (LET). We evaluate the particle dependence on the quenching effect in the small-size OSL dosimeter probe. Eu:BaFBr and Ce:CaF2 were adopted as OSL materials, and two types of small-size dosimeter were fabricated. We irradiated 290 MeV/u carbon ions, 150 MeV/u helium ions, and 225 MeV protons and measured the Bragg peak. The Eu:BaFBr small-size dosimeter showed the quenching effect in these three types of particle irradiation. The Ce:CaF2 small-size dosimeter showed the quenching effect only in carbon ion irradiation. The luminescence efficiencies of Eu:BaFBr were compared among these three charged particles. The quenching effect of Eu:BaFBr is independent of the irradiated particles

Intradermal administration of DNA vaccine targeting Omicron SARS-CoV-2 via pyro-drive jet injector provides the prolonged neutralizing antibody production via germinal center reaction

Abstract Emerging SARS-CoV-2 Omicron variants are highly contagious with enhanced immune escape mechanisms against the initially approved COVID-19 vaccines. Therefore, we require stable alternative-platform vaccines that confer protection against newer variants of SARS-CoV-2. We designed an Omicron B.1.1.529 specific DNA vaccine using our DNA vaccine platform and evaluated the humoral and cellular immune responses. SD rats intradermally administered with Omicron-specific DNA vaccine via pyro-drive jet injector (PJI) thrice at 2-week intervals elicited high antibody titers against the Omicron subvariants as well as the ancestral strain. Indeed, the Omicron B.1.1.529-specific antibody titer and neutralizing antibody were higher than that of other strains. Longitudinal monitoring indicated that anti-spike (ancestral and Omicron) antibody titers decreased toward 30 weeks after the first vaccination dose. However, neutralization activity remained unaltered. Germinal center formation was histologically detected in lymph nodes in rats immunized with Omicron DNA vaccine. Ancestral spike-specific immune cell response was slightly weaker than Omicron spike-specific response in splenocytes with Omicron-adapted DNA vaccine, evaluated by ELISpot assay. Collectively, our findings suggest that Omicron targeting DNA vaccines via PJI can elicit robust durable antibody production mediated by germinal center reaction against this new variant as well as partially against the spike protein of other SARS-CoV-2 variants

Modified DNA vaccine confers improved humoral immune response and effective virus protection against SARS-CoV-2 delta variant

Abstract Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to a global pandemic. New technologies have been utilized to develop several types of vaccines to prevent the spread of SARS-CoV-2 infection, including mRNA vaccines. Our group previously developed an effective DNA-based vaccine. However, emerging SARS-CoV-2 variants of concern (VOCs), such as the delta variant, have escaped mutations against vaccine-induced neutralizing antibodies. This suggests that modified vaccines accommodating VOCs need to be developed promptly. Here, we first modified the current DNA vaccine to enhance antigenicity. Compared with the parental DNA vaccine, the modified version (GP∆-DNA vaccine) induced rapid antibody production. Next, we updated the GP∆-DNA vaccine to spike glycoprotein of the delta variant (GP∆-delta DNA vaccine) and compared the efficacy of different injection routes, namely intramuscular injection using a needle and syringe and intradermal injection using a pyro-drive jet injector (PJI). We found that the levels of neutralizing antibodies induced by the intradermal PJI injection were higher than intramuscular injection. Furthermore, the PJI-injected GP∆-delta DNA vaccine effectively protected human angiotensin-converting enzyme 2 (hACE2) knock-in mice from delta-variant infection. These results indicate that the improved DNA vaccine was effective against emerging VOCs and was a potential DNA vaccine platform for future VOCs or global pandemics