Total syntheses of macleanine and lycoposerramine-S.

Total syntheses of fawcettimine-class Lycopodium alkaloids having an imino bridge between C5 and C13 were accomplished. Fawcettimine was first prepared in 10 steps from a known compound, and the characteristic structures, including the imino bridge, were constructed via the formation of a bridgehead imine.

A Rat Model to Study the Effects of Diet-Induced Obesity on Radiation-Induced Mammary Carcinogenesis.

A detailed understanding of the relationship between radiation-induced breast cancer and obesity is needed for appropriate risk management and to prevent the development of a secondary cancer in patients who have been treated with radiation. Our goal was to develop an animal model to study the relationship by combining two existing Sprague-Dawley rat models of radiation-induced mammary carcinogenesis and diet-induced obesity. Female rats were fed a high-fat diet for 4 weeks and categorized as obesity prone or obesity resistant based on their body weight at 7 weeks of age, at which time the rats were irradiated with 4 Gy. Control rats were fed a standard diet and irradiated at the same time and in the same manner. All rats were maintained on their initial diets and assessed for palpable mammary cancers once a week for the next 30 weeks. The obesity-prone rats were heavier than those in the other groups. The obesity-prone rats were also younger than the other animals at the first detection of mammary carcinomas and their carcinoma weights were greater. A tendency toward higher insulin and leptin blood levels were observed in the obesity-prone rats compared to the other two groups. Blood angiotensin II levels were elevated in the obesity-prone and obesity-resistant rats. Genes related to translation and oxidative phosphorylation were upregulated in the carcinomas of obesity-prone rats. Expression profiles from human breast cancers were used to validate this animal model. As angiotensin is potentially an important factor in obesity-related morbidities and breast cancer, a second set of rats was fed in a similar manner, irradiated and then treated with an angiotensin-receptor blocker, losartan and candesartan. Neither blocker altered mammary carcinogenesis; analyses of losartan-treated animals indicated that expression of renin in the renal cortex and of Agtr1a (angiotensin II receptor, type 1) in cancer tissue was significantly upregulated, suggesting the presence of compensating mechanisms for blocking angiotensin-receptor signaling. Thus, obesity-related elevation of insulin and leptin blood levels and an increase in available energy may facilitate sustained protein synthesis in cancer cells, which is required for rapid cancer development.

Optimal radiation shielding for beta and bremsstrahlung radiation emitted by (89)Sr and (90)Y: validation by empirical approach and Monte Carlo simulations.

OBJECTIVE: High-energy beta emitters such as Strontium-89 ((89)Sr) and Yttrium-90 ((90)Y) are becoming increasingly popular nuclear therapy sources in Japan for treating cancer. Various characteristics of materials must be considered when designing radiation protection device for high-energy beta emitters. We empirically measured and simulated dose equivalents of beta and bremsstrahlung radiation arising from (89)Sr and (90)Y radiation shielded with various materials and determined optimal shielding materials against these sources. METHODS: The dose equivalents of (89)Sr and (90)Y determined experimentally using an ionization chamber survey meter were compared with those of Monte Carlo simulations. The relative dose equivalents of beta and bremsstrahlung radiation separately transmitted by changing the thickness of acrylic, aluminum, iron, lead and tungsten shielding materials were simulated. RESULTS: Dose equivalents were consistent between the empirical measurements and the simulation to within ±5%. Shielding ability was more effective in the order of tungsten, lead, iron, aluminum and acrylic against both (89)Sr and (90)Y. The amount of beta and bremsstrahlung radiation transmitted through tungsten and lead was relatively small. Although such high-density material generates much bremsstrahlung radiation, it absorbs the bremsstrahlung radiations. CONCLUSIONS: Tungsten was the optimal material for efficient shielding against (89)Sr and (90)Y radiation and preferable among operators. The present findings provide useful information about how to define an appropriate shielding strategy for high-energy beta emitters.

[Technical features and roles of cobalt-57 flood sources for daily quality control of gamma cameras].

Quality control (QC) detects changes in the performance of gamma cameras that could adversely affect interpretations of clinical studies. We used plate and sheet (57)Co flood sources to measure extrinsic uniformity during daily QC. Each source, when placed on the top of a collimated detector, allowed the acquisition of uniform images from both detectors, thus reducing the amount of time needed to perform daily QC. No serious problems with the gamma camera system were revealed by visual checks, and changes in detector sensitivity were rapidly determined by observing daily variations in the measured values of extrinsic uniformity. Furthermore, (57)Co flood sources confer advantages in that they shorten the time required for preparation of flood sources and reduce the consequent exposure of medical staff to radiation.

Validation of novel calibration scheme with traceable point-like (22)Na sources on six types of PET scanners.

OBJECTIVE: To improve the reliability and convenience of the calibration procedure of positron emission tomography (PET) scanners, we have been developing a novel calibration path based on traceable point-like sources. When using (22)Na sources, special care should be taken to avoid the effects of 1.275-MeV γ rays accompanying ß (+) decays. The purpose of this study is to validate this new calibration scheme with traceable point-like (22)Na sources on various types of PET scanners. METHOD: Traceable point-like (22)Na sources with a spherical absorber design that assures uniform angular distribution of the emitted annihilation photons were used. The tested PET scanners included a clinical whole-body PET scanner, four types of clinical PET/CT scanners from different manufacturers, and a small-animal PET scanner. The region of interest (ROI) diameter dependence of ROI values was represented with a fitting function, which was assumed to consist of a recovery part due to spatial resolution and a quadratic background part originating from the scattered γ rays. RESULTS: The observed ROI radius dependence was well represented with the assumed fitting function (R (2) > 0.994). The calibration factors determined using the point-like sources were consistent with those by the standard cross-calibration method within an uncertainty of ±4 %, which was reasonable considering the uncertainty in the standard cross-calibration method. CONCLUSION: This novel calibration scheme based on the use of traceable (22)Na point-like sources was successfully validated for six types of commercial PET scanners.

[Relationship between image quality and cross-sectional area of phantom in three-dimensional positron emission tomography scan].

The image quality in (18)FDG PET/CT often degrades as the body size increases. The purpose of this study was to evaluate the relationship between image quality and the body size using original phantoms of variable cross-sectional areas in PET/CT. We produced five water phantoms with different cross-sectional areas. The long axis of phantom was 925 mm, and the cross-sectional area was from 324 to 1189 cm(2). These phantoms with the sphere (diameter 10 mm) were filled with (18)F-FDG solution. The radioactivity concentration of background in the phantom was 1.37, 2.73, 4.09 and 5.46 kBq/mL. The scanning duration was 30 min in list mode acquisition for each measurement. Background variability (N(10 mm)), noise equivalent count rates (NECR(phantom)), hot sphere contrast (Q(H,10 mm)) as physical evaluation and visual score of sphere detection were measured, respectively. The relationship between image quality and the various cross-sectional areas was also analyzed under the above-mentioned conditions. As cross-sectional area increased, NECR(phantom) progressively decreased. Furthermore, as cross-sectional area increased, N(10 mm) increased and Q(H,10 mm) decreased. Image quality became degraded as body weight increased because noise and contrast contributed to image quality. The visual score of sphere detection deteriorated in high background radioactivity concentration because a false positive detection in cross-sectional area of the phantom increased. However, additional increases in scanning periods could improve the visual score. We assessed tendencies in the relationship between image quality and body size in PET/CT. Our results showed that time adjustment was more effective than dose adjustment for stable image quality of heavier patients in terms of the large cross-sectional area.

[Respiratory management of CT-transmission for accuracy fusion in PET/CT: a comparison between normal expiration and free breathing in 600 experiences].

Image misregistration can occur in fusion PET/CT, because of motion artifacts caused by the management of respiration. The standard imaging protocol of the CT component of PET/CT is normal expiration (NormExp) or free breathing (FB). The objective of this study was to compare NormExp and FB for the optimal breathing protocol for PET/CT scans. A total of 600 consecutive patients were examined using lutetium oxyorthosilicate (LSO)-based PET/CT. CT was acquired during NormExp (i.e., the level reached when the patient exhaled without forcing expiration and then held the breath) in 300 patients and during FB in 300 patients. The profile of liver measured along body axis was assessed. The distance of profile centers between the PET image and the CT image was measured. The misalignment between profile centers (PET) and profile centers (CT) was compared between NormExp and FB using the histogram of patients. An F test was used to test if the variances of two misalignments are equal. Next, the relationship between misalignment and age was evaluated in two managements of respiration. There was no significant difference between NormExp and FB in the histogram. However, significant misalignments (>10 cm) were found with NormExp. Patient age may have influenced the mismatch. FB is recommended for geriatric patients during acquisition of attenuation correction CT data sets.