Ten-Gram-Scale Total Synthesis of the Anticancer Drug Candidate E7130 to Supply Clinical Trials.

E7130 is a novel drug candidate with an exceedingly complex chemical structure of the halichondrin class, discovered by a total synthesis approach through joint research between the Kishi group at Harvard University and Eisai. Only 18 months after completion of the initial milligram-scale synthesis, ten-gram-scale synthesis of E7130 was achieved, providing the first good manufacturing practice (GMP) batch to supply clinical trials. This paper highlights the challenges in developing ten-gram-scale synthesis from the milligram-scale synthesis.

[Propose for the Benchmark Dose (BD) for the Optimization of Protection in Medical Exposure in General Radiography].

The goal of this research was to create the most appropriate index dose for the optimization of protection in medical exposure in general radiography in Kanagawa prefecture. We distributed questionnaires to 272 medical institutions in Kanagawa prefecture. The investigation period was from October 2015 to February 2016. Entrance surface dose (ESD) was used as the index dose. Investigated regions in general radiography were the adult chest, adult abdomen, and infant chest (anterior-posterior projections for all regions). The effective response rate was 35%. ESD was significantly lower with a flat panel detector (FPD) than with computed radiography (CR) in all regions (adult chest and abdomen: p<0.001; infant chest: p<0.05) [e.g., mean (±standard deviation) ESD in the adult chest was 0.16±0.06 mGy with FPD and 0.24±0.10 mGy with CR]. In the infant chest with CR, ESD was significantly higher using a grid (0.15±0.07 mGy) compared to not using a grid (0.10±0.05 mGy; p<0.05). Based on these results, we propose the benchmark dose of each medical equipment, such as adult chest: FPD, 0.2 mGy; CR, 0.3 mGy.

[Evaluating photonuclear activation for clearance of decommissioned medical linear accelerators].

In a linear accelerator (linac) that operates at greater than an accelerating energy of 10 MV, neutrons are generated by a photonuclear reaction and the head section of the linac becomes radioactive. The purpose of this research is to obtain data for ensuring the safety of linac decommissioning and upgrading. The decommissioned linac investigated in this study was a Clinac 2100 C/D (Varian) installed in April 1999. Its total time of use was 2757.7 h (equivalent to 496,386 Gy). The dosage for its last three months of use was 7213.67 Gy. After being allowed to sit for a 7-day cooling period, the apparatus was disassembled and the parts of the gantry head portion were removed. The ambient dose equivalent rates, H*(10), (microSv/h) from the removed parts were measured in air, at a location with low background, by using a gamma ray scintillation survey meter. The target was also analyzed with an HP-Ge semiconductor detector, in order to identify the nuclides responsible for the observed radiation. On day 7 after the last use of the linac, the ambient dose equivalent rates, H*(10), (microSv/h) in air at the surface of all parts, except the target and the beryllium window, were within the limit of normal background radiation. The measured value (microSv/h) for the beryllium window decreased to within the background limit on day 10. The measured value (microSv/h) of the target decreased to about 1.5 times the background on day 19. At a distance of 10 cm, all the parts were within the background limit after the initial 7-day cooling period. In the analysis of the target with the HP-Ge semiconductor detector, peaks at 125, 333, 352, 356, 426, 511, 583, 609, 689, 811, 835, 911, 969, 1091, 1099, 1120, 1173, 1238, 1292, 1333, 1461 and 1764keV were detected on day 23. Seven months after the linac was last used, peaks were detected at 352, 511, 583, 609, 835, 911, 969, 1120, 1173, 1238, 1333, 1461 and 1764 keV. From these results, the natural radioactive nuclides can be assigned as 40K, 208Tl, 214Pb, 214Bi and 228Ac; the short half-life nuclides can be assigned as 59Fe, 58Co, 185W and 196Au; and the long half-life nuclides can be assigned as 54Mn and 60Co. These results show that photonuclear activation of parts is important in regard to clearance. Currently, there are no regulations that specify criteria for evaluating radioactivation. Such criteria are needed to establish suitable protocols for the clearance of radioactivated materials.