This paper proposes a maximum torque per ampere control strategy for direct-torque-controlled interior permanent magnet synchronous motor drives. The proposed method is based on the solutions of a ...quartic equation, a motor model in the d-q rotating frame often used for the synchronous motor controllers, and a well-known equation for maximum torque per ampere control. Therefore, the proposed method does not use a lookup table that depends on parameters of the motor and that has to be created in advance. In addition, the proposed method can use the estimated parameters. Particularly, the variations of the d- and q-axes inductances can be estimated when the inductances are modeled as the functions of the d- and q-axes current. The simulation results validate that the proposed method can achieve the maximum torque per ampere control. In addition, the simulation and experimental results verify the accuracy improvement of the maximum torque per ampere control with the iterated calculation.
Purpose
Fibroblast activation protein (FAP), which has high expression in cancer-associated fibroblasts of epithelial cancers, can be used as a theranostic target. Our previous study used
64
Cu and
...225
Ac-labelled FAP inhibitors (FAPI-04) for a FAP-expressing pancreatic cancer xenograft imaging and therapy. However, the optimal therapeutic radionuclide for FAPI needs to be investigated further. In this study, we evaluated the therapeutic effects of beta-emitter (
177
Lu)-labelled FAPI-46 and alpha-emitter (
225
Ac)-labelled FAPI-46 in pancreatic cancer models.
Methods
PET scans (1 h post injection) were acquired in PANC-1 xenograft mice (
n
= 9) after the administration of
18
FFAPI-74 (12.4 ± 1.7 MBq) for the companion imaging. The biodistribution of
177
LuFAPI-46 and
225
AcFAPI-46 were evaluated in the xenograft model (total
n
= 12). For the determination of treatment effects,
177
LuFAPI-46 and
225
AcFAPI-46 were injected into PANC-1 xenograft mice at different doses: 3 MBq (
n
= 6), 10 MBq (
n
= 6), 30 MBq (
n
= 6), control (
n
= 4) for
177
LuFAPI-46, and 3 kBq (
n
= 3), 10 kBq (
n
= 2), 30 kBq (
n
= 6), control (
n
= 7) for
225
AcFAPI-46. Tumour sizes and body weights were followed.
Results
18
FFAPI-74 showed rapid clearance by the kidneys and high accumulation in the tumour and intestine 1 h after administration.
177
LuFAPI-46 and
225
AcFAPI-46 also showed rapid clearance by the kidneys and relatively high accumulation in the tumour at 3 h. Both
177
LuFAPI-46 and
225
AcFAPI-46 showed tumour-suppressive effects, with a mild decrease in body weight. The treatment effects of
177
LuFAPI-46 were relatively slow but lasted longer than those of
225
AcFAPI-46.
Conclusion
This study suggested the possible application of FAPI radioligand therapy in FAP-expressing pancreatic cancer. Further evaluation is necessary to find the best radionuclide with shorter half-life, as well as the combination with therapies targeting tumour cells directly.
Objective
Astatine (
211
At) is a promising alpha emitter as an alternative to iodine (
131
I). We are preparing the first-in-human (FIH) clinical trial of targeted alpha therapy for differentiated ...thyroid cancer in consultation with Pharmaceuticals and Medical Devices Agency. Here, we performed an extended single-dose toxicity examination under a reliability standard, as a preclinical safety assessment of
211
AtNaAt to determine the FIH dose.
Methods
211
AtNaAt solution was injected into normal 6-week-old mice (male (
n
= 50) and female (
n
= 50), body weight: male 33.2 ± 1.7 g, female 27.3 ± 1.5 g), which were then divided into four groups: 5 MBq/kg (
n
= 20), 20 MBq/kg (
n
= 20), 50 MBq/kg (
n
= 30), saline control (
n
= 30). The mice were followed up for 5 days (primary evaluation point for acute toxicity:
n
= 80) or 14 days (
n
= 20: evaluation point for recovery) to monitor general condition and body weight change. At the end of the observation period, necropsy, blood test, organ weight measurement, and histopathological examination were performed. For body weight, blood test, and organ weight, statistical analyses were performed to compare data between the control and injected groups.
Results
No abnormal findings were observed in the general condition of mice. In the 50 MBq/kg group, males (days 3 and 5) showed a significant decrease in body weight compared with the control. However, necropsy did not differ significantly beyond the range of spontaneous lesions. In the blood test, males (50 MBq/kg) and females (50 MBq/kg) showed a decrease in white blood cell and platelet counts on day 5, and recovery on day 14. In the testis, a considerable weight decrease was observed on day 14 (50 MBq/kg), and multinucleated giant cells were observed in all mice, indicating a significant change related to the administration of
211
AtNaAt.
Conclusions
In the extended single-dose toxicity study of
211
AtNaAt, administration of high doses resulted in weight loss, transient bone marrow suppression, and pathological changes in the testis, which require consideration in the FIH clinical trial.
Astatine-211 (
At)-labeled phenylalanine is expected to be a promising agent for targeted alpha-particle therapy for the treatment of patients with glioma. The existing reactions to prepare the ...labeled compound usually require organic solvents and metals that are toxic and hazardous to the environment. In this study, we developed a novel method wherein astatination was realized via the substitution of
At for a dihydroxyboryl group coupled to phenylalanine.
At4-astato-L-phenylalanine was obtained as the carrier-free product in aqueous medium in high radiochemical yields (98.1 ± 1.9%, n = 5). The crude reaction mixture was purified by solid-phase extraction, and the radiochemical purity of the product was 99.3 ± 0.7% (n = 5). The high yield and purity were attributed to the formation of
AtAtI and AtI
as the reactive intermediates in the astatination reaction. The reaction did not require any organic solvents or toxic reagents, suggesting that this method is suitable for clinical applications.
Elemental analysis based on muonic X-rays resulting from muon irradiation provides information about bulk material composition without causing damage, which is essential in the case of precious or ...otherwise unreachable samples, such as in archeology and planetary science. We developed a three-dimensional (3D) elemental analysis technique by combining the elemental analysis method based on negative muons with an imaging cadmium telluride double-sided strip detector (CdTe-DSD) designed for the hard X-ray and soft Formula: see text-ray observation. A muon irradiation experiment using spherical plastic samples was conducted at the Japan Proton Accelerator Research Complex (J-PARC); a set of projection images was taken by the CdTe-DSD, equipped with a pinhole collimator, for different sample rotation angles. The projection images measured by the CdTe-DSD were utilized to obtain a 3D volumetric phantom by using the maximum likelihood expectation maximization algorithm. The reconstructed phantom successfully revealed the 3D distribution of carbon in the bulk samples and the stopping depth of the muons. This result demonstrated the feasibility of the proposed non-destructive 3D elemental analysis method for bulk material analysis based on muonic X-rays.
In this paper, a reference stator flux linkage calculation method is proposed for realizing maximum efficiency operation in direct‐torque‐controlled interior permanent magnet synchronous motor ...(IPMSM) drives. The proposed method is based on the solutions of a quartic equation, a motor model in the d‐q rotating frame widely used for synchronous motor controllers, and a well‐known equation for maximum efficiency operation. Therefore, the proposed method uses neither any approximation function nor any look‐up table that depends on the parameters of the motor, which has to be created in advance. Simulation results validate that the proposed methods can achieve maximum efficiency operation in IPMSM drives.
At is a high-energy α-ray emitter with a relatively short half-life and a high cytotoxicity for cancer cells. Its dispersion can be imaged using clinical scanners, and it can be produced in ...cyclotrons without the use of nuclear fuel material. This study investigated the biodistribution and the antitumor effect of
At-labeled gold nanoparticles (
At-AuNP) administered intratumorally.
AuNP with a diameter of 5, 13, 30, or 120 nm that had been modified with poly (ethylene glycol) methyl ether (mPEG) thiol and labeled with
At (
At-AuNP-S-mPEG) were incubated with tumor cells, or intratumorally administered to C6 glioma or PANC-1 pancreatic cancers subcutaneously transplanted into rodent models. Systemic and intratumoral distributions of the particles in the rodents were then evaluated using scintigraphy and autoradiography, and the changes in tumor volumes were followed for about 40 days.
At-AuNP-S-mPEG was cytotoxic when it was internalized by the tumor cells. After intratumoral administration,
At-AuNP-S-mPEG became localized in the tumor and did not spread to systemic organs during a time period equivalent to 6 half-lives of
At. Tumor growth was strongly suppressed for both C6 and PANC-1 by
At-AuNP-S-mPEG. In the C6 glioma model, the strongest antitumor effect was observed in the group treated with
At-AuNP-S-mPEG with a diameter of 5 nm.
The intratumoral single administration of a simple nanoparticle,
At-AuNP-S-mPEG, was shown to suppress the growth of tumor tissue strongly in a particle size-dependent manner without radiation exposure to other organs caused by systemic spread of the radionuclide.
Astatine (211At) is an alpha-emitter with a better treatment efficacy against differentiated thyroid cancer compared with iodine (131I), a conventional beta-emitter. However, its therapeutic ...comparison has not been fully evaluated. In this study, we compared the therapeutic effect between 211AtNaAt and 131INaI. In vitro analysis of a double-stranded DNA break (DSB) and colony formation assay were performed using K1-NIS cells. The therapeutic effect was compared using K1-NIS xenograft mice administered with 211AtNaAt (0.4 MBq (n = 7), 0.8 MBq (n = 9), and 1.2 MBq (n = 4)), and 131INaI (1 MBq (n = 4), 3 MBq (n = 4), and 8 MBq (n = 4)). The 211AtNaAt induced higher numbers of DSBs and had a more reduced colony formation than 131INaI. In K1-NIS mice, dose-dependent therapeutic effects were observed in both 211AtNaAt and 131INaI. In 211AtNaAt, a stronger tumour-growth suppression was observed, while tumour regrowth was not observed until 18, 25, and 46 days after injection of 0.4, 0.8, and 1.2 MBq of 211AtNaAt, respectively. While in 131INaI, this was observed within 12 days after injection (1, 3, and 8 MBq). The superior therapeutic effect of 211AtNaAt suggests the promising clinical applicability of targeted alpha therapy using 211AtNaAt in patients with differentiated thyroid cancer refractory to standard 131INaI treatment.
Phenylalanine derivatives, which target tumors especially through L-type amino acid transporter-1 (LAT1), have elicited considerable attention. In this study, we evaluated the treatment effect of ...phenylalanine labeled with the alpha emitter astatine (
At-PA) in tumor bearing mice. The C6 glioma, U-87MG, and GL261 cell lines were subjected to a cellular
At-PA uptake analysis that included an evaluation of the uptake inhibition by the system L amino acid transporter inhibitor 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid (BCH). BCH significantly inhibited para-
At-PA uptake in C6 glioma (12.2 ± 0.8%), U-87MG (27.6 ± 1.1%), and GL261 (12.6 ± 2.0%) cells compared to baseline, suggesting an uptake contribution by system L amino acid transporters. Subsequently, xenograft and allograft models were prepared by subcutaneously injecting C6 glioma (
= 12) or GL-261 cells (
= 12), respectively. C6 glioma mice received three
At-PA doses (0.1, 0.5, or 1 MBq,
= 3/dose), while GL261 mice received one high dose (1 MBq,
= 7).
At-PA exhibited a tumor growth suppression effect in C6 glioma models in a dose-dependent manner as well as in GL-261 models. This phenylalanine derivative labeled with astatine may be applicable as an alpha therapy that specifically targets system L amino acid transporters.
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