JFE Engineering Corp.

Novel diagnostic and therapeutic options are urgently needed for patients with metastatic castration-resistant prostate cancer (CRPC). PSMA-617 is one of the most promising ligands that bind to prostate specific membrane antigen (PSMA), the cell surface biomarker of CRPC. Of the radiolabeled PSMA ligands developed to date, [⁶⁸Ga]Ga-PSMA-617 is most commonly used for PSMA positron emission tomography (PET) prior to radioligand therapy (RLT) with [¹⁷⁷Lu]Lu-PSMA-617. However, the presence of ⁶⁸Ga radioactivity (half-life 68 m) in urine at the early PET imaging time point complicates optimization of the therapeutic dose of PSMA-617 labeled with ¹⁷⁷Lu (half-life 6.7 d). Thus, PET imaging with the long-lived positron emitter ⁸⁹Zr (half-life 3.3 d) would be better suited in order to optimize the dose of [¹⁷⁷Lu]Lu-PSMA-617 as ⁸⁹Zr PET allows scans after excretion of the radioactive urine. Until now, PSMA-617 could not be radiolabeled with ⁸⁹Zr with high radiochemical yield due to poor incorporation of ⁸⁹Zr into 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA). Here we report a novel method for radiolabeling PSMA-617 with ⁸⁹Zr and the preliminary results of small-animal PET with [⁸⁹Zr]Zr-PSMA-617.

We labeled PSMA-617 with ⁸⁹Zr in a 1:1 mixture of DMSO and HEPES buffer at 90 °C for 30 min, followed by quality control analysis by HPLC. We then determined the dissociation constant (K_d) and logD values of [⁸⁹Zr]Zr-PSMA-617. We obtained PET images of [⁸⁹Zr]Zr-PSMA-617 at 24 h in mice bearing both LNCaP (PSMA-positive) and PC-3 (PSMA-negative) tumors (N = 5). The ex vivo [⁸⁹Zr]Zr-PSMA-617 biodistribution was then examined separately using tissue samples of LNCaP-bearing mice at 2 h (N = 4) and 24 h (N = 4).

[⁸⁹Zr]Zr-PSMA-617 was prepared with a radiochemical yield of 70 ± 9%. The K_d value was 6.8 ± 3.5 nM. The logD value was -4.05 ± 0.20. PET images showed the highest uptake in LNCaP tumors (maximum standardized uptake value, SUV_max = 0.98 ± 0.32) and low uptake in kidneys (SUV_max = 0.18 ± 0.7) due to the absence of urine radioactivity.

[⁸⁹Zr]Zr-PSMA-617 was successfully prepared using DMSO and HEPES buffer. [⁸⁹Zr]Zr-PSMA-617 visualized PSMA-positive LNCaP tumors in the absence of radioactive urine 24 h p.i.

This method of radiolabeling PSMA-617 with ⁸⁹Zr using DMSO would be suitable for future clinical trials. Prediction of radiation dose by using [⁸⁹Zr]Zr-PSMA-617 leads to the safe and effective RLT with [¹⁷⁷Lu]Lu-PSMA-617.

Following the 45th Global Warming Countermeasures Promotion Headquarters held on Apr. 22, 2021, Japan announced its goal of reducing greenhouse gas emissions in 2030 by 46% compared to 2013.This paper describes characteristics of the multi-raw material BIC made from waste biomass and mechanism of high-temperature gasification direct melting furnace that can use it as fuel.As the application of coal alternative fuels is desired in existing coal-based fuel utilization processes toward realization of carbon-neutral society, it is important to appropriately combine applicable biomass fuels and their utilization processes.In this paper, authors described the multi-material BIC and high-temperature gasification direct melting furnace, and introduced a demonstration example of combining them.In addition, by combining carbonized biomass fuel with non-carbonized biomass fuel such as BIC, coke can be completely replaced.On the other hand, possibility has been demonstrated by devising both production and utilization of biomass fuel, and further development is expected in the future.

The present study investigated the effect of a compressive mean stress on the fatigue strength and crack growth behavior using smooth and notched specimens, resp., for aluminum alloys of 6061, 6066 and 7075 in dry and humid air environments by an ultrasonic fatigue testing machine.Very high cycle fatigue strength of the smooth specimen of 6061 and 6066 alloys were insensitive to the relative humidity of the air, while it was much reduced in humid air than in dry air for 7075 alloy.The influence of the compressive mean stress on the fatigue strength was small for all the alloys regardless of the relative humidity.Crack growth characteristics tested by the notched specimen with precrack revealed that the crack began to grow under stress intensity factor range, ΔK, constant condition when the tensile component of ΔK, i.e. maximum stress intensity factor, Kmax, exceeded the threshold value of effective stress intensity factor range, ΔKeff,th, obtained by crack growth tests at high stress ratio.Crack growth life was predicted by the fatigue crack growth characteristics obtained by the latter tests.Also, it was compared with the fatigue strength characteristics and the small crack initiation and growth behavior obtained by the former tests.The results suggested that the crack closure point reduced to be compression side by the compressive mean stress.Therefore, a fatigue life under compressive mean stress could be evaluated conservatively by a full load range including compressive component.