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The diagnostic reference levels (DRLs) are one of several effective tools for optimizing nuclear medicine examinations and reducing patient exposure. With the advances in imaging technology and alterations of examination protocols, the DRLs must be reviewed periodically. The first DRLs in Japan were established in 2015, and since 5 years have passed, it is time to review and revise the DRLs. We conducted a survey to investigate the administered activities of radiopharmaceuticals and the radiation doses of computed tomography (CT) in hybrid CT accompanied by single photon emission computed tomography (SPECT)/CT and positron emission tomography (PET)/CT. We distributed a Web-based survey to 915 nuclear medicine facilities throughout Japan and survey responses were provided by 256 nuclear medicine facilities (response rate 28%). We asked for the facility's median actual administered activity and median radiation dose of hybrid CT when SPECT/CT or PET/CT was performed for patients with standard habitus in the standard protocol of the facility for each nuclear medicine examination. We determined the new DRLs based on the 75th percentile referring to the 2015 DRLs, drug package inserts, and updated guidelines. The 2020 DRLs are almost the same as the 2015 DRLs, but for the relatively long-lived radionuclides, the DRLs are set low due to the changes in the Japanese delivery system. There are no items set higher than the previous values. Although the DRLs determined this time are roughly equivalent to the DRLs used in the US, overall they tend to be higher than the European DRLs. The DRLs of the radiation dose of CT in hybrid CT vary widely depending on each imaging site and the purpose of the examination.

Abstract:The enterohepatic recycling of a drug consists of its biliary excretion and intestinal reabsorption, which is sometimes accompanied by hepatic conjugation and intestinal deconjugation reactions. b-Glucuronidase, an intestinal bacteria-produced enzyme, can break the bond between a biliary excreted drug and glucuronic acid. Antibiotics such as ciprofloxacin can reduce the enterohepatic recycling of glucuronide-conjugated drugs. In this study, we established an in vitro system to evaluate the b-glucuronidase-mediated deconjugation of the irinotecan metabolite SN-38-G to its active SN-38 form and the effect of ciprofloxacin thereon. SN-38 formation increased in a time-dependent manner from 5 to 30 min. in the presence of b-glucuronidase. Ciprofloxacin and phenolphthalein-b-D-glucuronide (PhePG), a typical b-glucuronidase substrate, significantly decreased SN-38-G deconjugation and, hence SN-38 formation. Similarly, the antibiotics enoxacin and gatifloxacin significantly inhibited the conversion of SN-38-G to SN-38, which was not observed for levofloxacin, streptomycin, ampicillin and amoxicillin/clavulanate. Ciprofloxacin showed a dose-dependent inhibitory effect on the b-glucuronidase-mediated conversion of SN-38-G to SN-38 with a half-maximal inhibitory concentration (IC 50 ) value of 83.8 lM. PhePG and ciprofloxacin afforded the inhibition in a competitive and non-competitive manner, respectively. These findings suggest that the reduction in the serum SN-38 concentration following co-administration of ciprofloxacin during irinotecan treatment is due, at least partly, to the decreased enterohepatic circulation of SN-38 through the non-competitive inhibition of intestinal b-glucuronidase-mediated SN-38-G deconjugation.Irinotecan is an anti-tumour drug frequently used in clinical practice for the treatment of various carcinomas such as colorectal cancer [1] and lung cancer [2]. In vivo, irinotecan is converted to the active metabolite SN-38 (7-ethyl-10-hydroxycamptothecin) by carboxylesterase in the liver microsomes. SN-38 exhibits anti-tumour effects by inhibiting type I topoisomerases in tumour cells [3]. Moreover, SN-38 is excreted into the gastrointestinal tract as a glucuronic acid conjugate (hereinafter SN-38-G) mainly via bile through the hepatic metabolic enzyme UDP-glucuronosyltransferase 1-1 (UGT1A1). SN-38-G is subsequently converted into its active form (SN-38) through deconjugation mediated by enteric bacteria-derived b-glucuronidase [4]. The presence of SN-38 in the gastrointestinal tract may cause diarrhoea as side effect by directly impairing certain functions of the gastrointestinal tract. Thus, in clinical practice, drugs that inhibit the deconjugation of glucuronic acid in the gastrointestinal tract are sometimes co-administered as supportive therapy to reduce SN-38-related side effects [5]. Diarrhoeal is a dose-limiting factor in irinotecan treatment; long-term diarrhoea prevents the use of a sufficient dose of irinotecan, which may hinder irinotecan's therapeutic efficacy. Thus far, we ...

The impact of lower serum albumin levels on teicoplanin pharmacokinetics has not been previously determined. The authors assessed the relationship between total and free concentrations of teicoplanin in serum samples obtained from patients receiving teicoplanin therapy for Gram-positive bacterial infections. In addition, the authors determined the contribution of serum albumin concentrations to the unbound fraction of teicoplanin. One hundred ninety-eight serum samples were obtained from 65 patients undergoing routine therapeutic drug monitoring of teicoplanin. Free serum teicoplanin was separated by ultrafiltration, and total and free serum concentrations of teicoplanin were determined by a fluorescence polarization immunoassay. Regression analysis was then performed to build a prediction model for the free serum teicoplanin concentration from the total serum teicoplanin concentration and the serum albumin level using the first 132 samples. The predictive performance of this model was then tested using the next 66 samples. Free serum teicoplanin concentrations (Cf) (mug/mL) were predicted using a simple model constructed using total serum teicoplanin (Ct) (mug/mL) and albumin concentrations (ALB) (g/dL): Cf = Ct/(1 + 1.78 * ALB). This model could estimate free serum teicoplanin concentrations with a small bias and an acceptable error. The measured free level of teicoplanin will lie between 0.63 and 1.38 times the predicted concentration in 95% of cases. Serum albumin level plays a major role in the variability of the fraction unbound of teicoplanin. This model can reliably estimate free serum teicoplanin concentrations more easily than by using direct measurements.

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Silicon-hydrogen bonds in silicon oxide films were detected for the first time by applying surface-sensitive X-ray photoelectron spectroscopy and were confirmed by measuring infrared absorption. The areal density of silicon-hydrogen bonds in native oxides formed in a hot solution of HNO3 is estimated to be nearly 2×1014 cm-2, and is much larger than that formed in a solution with a composition of NH4OH:H2O2:H2O=1:1.4:4.

Atomic mixing in Si/Ge strained-layer superlattices is investigated by means of SIMS and XPS. The interfacial mixing is attributed to the surface segregation of Ge atoms during MBE growth of Si overlayers. It is demonstrated that the surface segregation is remarkably suppressed by depositing submonolayer Sb atoms on Ge layers prior to Si overgrowth and that Ge layers are confined to within 0.8 nm.

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