Newly-Developed Positron Emission Mammography (PEM) Device for the Detection of Small Breast Cancer.

Positron emission mammography (PEM) has higher detection sensitivity for breast cancer compared with whole-body positron emission tomography (PET) due to higher spatial resolution. We have developed a new PEM device with high resolution over a wide field of view. This PEM device comprises novel scintillation crystals, praseodymium-doped lutetium aluminum garnet (Pr:LuAG). In the present study, the clinical use of the newly developed PEM for the detection of small breast cancer was compared with that of the conventional PET-computed tomography (PET/CT). Eighty-two patients with breast cancer less than 20 mm (UICC T1) participated in this study, including 23 patients with T1a or T1b breast cancer (less than 10 mm). Histologically-proved lesions were examined by PET/CT and PEM on the same day after injection of [18F]fluoro-2-deoxy-2-fluoro-D-glucose ([18F]FDG), a marker of glycolytic activity. The newly developed PEM showed better sensitivity of cancer detection compared with PET/CT especially in case of the small T1a or T1b lesions. Moreover, when the conventional PET/CT and new PEM were combined, the detection sensitivity with [18F]FDG molecular imaging for T1 (N = 82) and T1a plus T1b breast cancer (N = 23) were 90% and 70%, respectively. The uptake of [18F]FDG was proportional to the histological malignancy of breast cancer. Using the newly-developed PEM with [18F]FDG, we are able to identify and characterize exactly the small breast tumors less than 10 mm in combination with the conventional PET/CT. These data indicate that PEM and PET/CT are synergic and complementary for the detection of small breast cancer.

Singing can improve speech function in aphasics associated with intact right basal ganglia and preserve right temporal glucose metabolism: Implications for singing therapy indication.

Clinically, we know that some aphasic patients can sing well despite their speech disturbances. Herein, we report 10 patients with non-fluent aphasia, of which half of the patients improved their speech function after singing training. We studied ten patients with non-fluent aphasia complaining of difficulty finding words. All had lesions in the left basal ganglia or temporal lobe. They selected the melodies they knew well, but which they could not sing. We made a new lyric with a familiar melody using words they could not name. The singing training using these new lyrics was performed for 30 minutes once a week for 10 weeks. Before and after the training, their speech functions were assessed by language tests. At baseline, 6 of them received positron emission tomography to evaluate glucose metabolism. Five patients exhibited improvements after intervention; all but one exhibited intact right basal ganglia and left temporal lobes, but all exhibited left basal ganglia lesions. Among them, three subjects exhibited preserved glucose metabolism in the right temporal lobe. We considered that patients who exhibit intact right basal ganglia and left temporal lobes, together with preserved right hemispheric glucose metabolism, might be an indication of the effectiveness of singing therapy.

Glucose Uptake Is Decreased in Affected Lower Leg Muscles of Hemiparetic Persons during Level Walking.

Stroke patients suffer from gait disturbance due to altered leg muscle actions. Many kinesiological studies have investigated muscle actions, but the metabolic activity of muscles in stroke patients remains to be investigated. We therefore evaluated energy consumption in lower extremity muscles during level walking in hemiparetic individuals. Glucose uptake was measured by positron emission tomography (PET) using (18)F-fluorodeoxyglucose ((18)F-FDG) in eight hemiparetic (mean age: 56 years) and 11 healthy (mean age: 26 years) participants. Standardized uptake ratio (SUR) was computed in each muscle to express the (18)F-FDG-uptake level. SUR was compared across gluteal, thigh, and lower leg muscles and across individual muscles within each muscle group. For each muscle, SUR was compared among the paretic limb of hemiparetic participants, the non-paretic limb of hemiparetic participants, and the right limb of healthy participants. In paretic limbs, mean SUR did not differ between the three muscle groups, or between individual muscles within each muscle group. SURs of paretic lower leg muscles and gluteus minimus muscle were significantly smaller than those of non-paretic limb and healthy participants (p < 0.05). In the non-paretic limb of hemiparetic participants, SUR of the lower leg muscles was larger than that of the thigh muscles (p < 0.05). Unexpectedly, SURs of medial hamstring and posterior tibial muscles were larger in the non-paretic limb of hemiparetic participants, compared to the right limb of healthy participants (p < 0.05). (18)F-FDG PET is useful to evaluate energy consumption levels of lower extremity muscles during level walking in hemiparetic individuals.

Restoration of accelerator facilities damaged by Great East Japan Earthquake at Cyclotron and Radioisotope Center, Tohoku University.

The Cyclotron and Radioisotope Center (CYRIC) of Tohoku University is a joint-use institution for education and research in a wide variety of fields ranging from physics to medicine. Accelerator facilities at the CYRIC provide opportunities for implementing a broad research program, including medical research using positron emission tomography (PET), with accelerated ions and radioisotopes. At the Great East Japan Earthquake on March 11, 2011, no human injuries occurred and a smooth evacuation was made in the CYRIC, thanks to the anti-earthquake measures such as the renovation of the cyclotron building in 2009 mainly to provide seismic strengthening, fixation of shelves to prevent the falling of objects, and securement of the width of the evacuation route. The preparation of an emergency response manual was also helpful. However, the accelerator facilities were damaged because of strong shaking that continued for a few minutes. For example, two columns on which a 930 cyclotron was placed were damaged, and thereby the 930 cyclotron was inclined. All the elements of beam transport lines were deviated from the beam axis. Some peripheral devices in a HM12 cyclotron were broken. Two shielding doors fell from the carriage onto the floor and blocked the entrances to the rooms. The repair work on the accelerator facilities was started at the end of July 2011. During the repair work, the joint use of the accelerator facilities was suspended. After the repair work was completed, the joint use was re-started at October 2012, one and a half years after the earthquake.

Effects of preceding stimulation on brain activation in response to colonic distention in humans.

OBJECTIVE: It has been suggested that the pattern of distension (moderate following mild and vice versa) might influence brain activation and the experience of hypersensitivity, offset analgesia, and anticipation. Nevertheless, how the pattern of stimulation affects sensitization and/or desensitization to visceral stimulation remains unknown. METHODS: In 45 nonclinical healthy participants (12 women, 33 men; 20-26 years old), brain processing of visceral sensation induced by colonic distension was examined using H2(15)O positron emission tomography. Subjective feelings regarding the stimuli were also measured. The descending colon was stimulated using six patterns of three bag pressures (0, 20, and 40 mm Hg). To evaluate the neural sensitization to visceral stimulation arising from the precedence effect, the effects of a 20- or 40-mm Hg distention after a sham or 20- or 40-mm Hg distension were analyzed using statistical parametric mapping. The level of significance was set at a voxelwise level of p < .0001, with cluster extent sizes of k > 50. RESULTS: The midbrain, insula, and cerebellum, were more strongly activated by a 20-mm Hg distension with a preceding 40-mm Hg distention than by a 20-mm Hg distention without a preceding stimulation (p < .0001). Conversely, a sham stimulation after the experience of an intense stimulation activated the midcingulate cortex, compared with a sham stimulation without the experience of actual visceral stimulation (p < .0001). CONCLUSIONS: By directly comparing different patterns of visceral stimuli, preceding visceral stimuli may affect neural sensitization and/or desensitization in humans, including elevated midbrain, insula, and midcingulate cortex.

Novel Auger-Electron-Emitting 191Pt-Labeled Pyrrole-Imidazole Polyamide Targeting MYCN Increases Cytotoxicity and Cytosolic dsDNA Granules in MYCN-Amplified Neuroblastoma.

Auger electrons can cause nanoscale physiochemical damage to specific DNA sites that play a key role in cancer cell survival. Radio-Pt is a promising Auger-electron source for damaging DNA efficiently because of its ability to bind to DNA. Considering that the cancer genome is maintained under abnormal gene amplification and expression, here, we developed a novel 191Pt-labeled agent based on pyrrole-imidazole polyamide (PIP), targeting the oncogene MYCN amplified in human neuroblastoma, and investigated its targeting ability and damaging effects. A conjugate of MYCN-targeting PIP and Cys-(Arg)3-coumarin was labeled with 191Pt via Cys (191Pt-MYCN-PIP) with a radiochemical purity of >99%. The binding potential of 191Pt-MYCN-PIP was evaluated via the gel electrophoretic mobility shift assay, suggesting that the radioagent bound to the DNA including the target sequence of the MYCN gene. In vitro assays using human neuroblastoma cells showed that 191Pt-MYCN-PIP bound to DNA efficiently and caused DNA damage, decreasing MYCN gene expression and MYCN signals in in situ hybridization analysis, as well as cell viability, especially in MYCN-amplified Kelly cells. 191Pt-MYCN-PIP also induced a substantial increase in cytosolic dsDNA granules and generated proinflammatory cytokines, IFN-α/ß, in Kelly cells. Tumor uptake of intravenously injected 191Pt-MYCN-PIP was low and its delivery to tumors should be improved for therapeutic application. The present results provided a potential strategy, targeting the key oncogenes for cancer survival for Auger electron therapy.

Quantitative evaluation of patch test reactions: a comparison between visual grading and erythema index image analysis.

BACKGROUND/AIMS: The interpretation of patch test reactions may vary between examiners. As test results are graded, an issue also arises when differing degrees of erythema are placed in the same grade. The purpose of this study was to quantitatively evaluate the degree of erythema in patch tests using image analysis and to study the usefulness of this method by comparing it with visual grading. METHODS: A total of 121 Japanese patients were patch tested with various materials. At 48 h, digital photographs of the patch test areas were taken, in addition to a visual evaluation by dermatologists. Digital images of the areas were converted to erythema index (EI) images using image processing and both EI and ΔEI (the difference between the patch test site and adjacent normal skin) values of the patch test sites were compared with the corresponding visual grades. RESULTS: An excellent linear correlation (r=0.95) was found between ΔEI and visual grades, although EI also significantly correlated with visual grades. There were significant differences (P<0.0001-0.05) between the mean ΔEI values of any two adjacent visual grades. CONCLUSION: ΔEI values derived from image processing appear to be suitable for the quantitative evaluation of erythema in patch tests. This method may be helpful in overcoming the subjectiveness of visual evaluation and for training non-experts in patch testing.

Relevance of the directionality of skin elasticity to aging and sagging of the face.

BACKGROUND: Forces acting in facial skin have been suggested to show directionality. Non-invasive methods of measuring this directionality may thus provide information related to aging processes. The Reviscometer(®) RVM600 device is capable of measuring directionality of forces on the skin. This device has not been used previously in a published study to evaluate changes in directionality of forces on facial skin with aging. AIM: The first objective of this pilot study was to investigate relationships between mechanical directionality using the Reviscometer(®) RVM600, the Cutometer(®) MPA580, and aging of the facial skin in a supine position. In addition, the study investigated relationships between mechanical directionality and 'skin sagging,' which may be caused by gravity. To validate this as a new measurement of mechanical directionality, we also performed double-blinded trials on two groups of subjects, with one group using a product containing an anti-aging substance and the other group using a placebo product without an anti-aging substance. METHODS: We examined 91 healthy Japanese women with a mean age of 48.5 years (range, 20-79 years) at the three sites on the face using the Reviscometer(®) RVM600 and the Cutometer(®) MPA580, and evaluation was performed for skin sagging in September and November 2008, and January 2009. The Reviscometer(®) RVM600 was used to measure resonance-running time (RRT) every 10° from 0° to 350°. Evaluation of skin sagging was undertaken by making marks on the face and using face photographs taken in both sitting and supine positions to calculate the sagging index. Usage testing was conducted on 38 healthy Japanese women in a double-blinded study with one group, using a preparation containing Yomogi AGEs Clearing (YAC) extract and another group using the same preparation without the YAC extract from October 2008 to April 2009. Mean age of these subjects was 44.0 years (range, 30-60 years). Measurements were taken at the three sites on the face using the Reviscometer(®) RVM600 and the Cutometer(®) MPA580 and sagging index. RESULTS: A significant correlation was identified between RRT parameters and subject age at all three measurement sites. Significant correlations between sagging index and RRT values were found for 110-170° and 290-350° only at the center of the cheek. Significant differences in RRT values were noted for 110-150° and 300-350° at this site between subjects with and without the use of YAC extract. A similar trend was found in sagging index for this site alone between subjects with and without YAC extract. CONCLUSION: The use of non-invasive procedures to measure skin mechanical parameters on the face in all directions may evaluate aging and effective preventive and restorative support.

Cerebral metabolic changes in men after chiropractic spinal manipulation for neck pain.

BACKGROUND: Chiropractic spinal manipulation (CSM) is an alternative treatment for back pain. The autonomic nervous system is often involved in spinal dysfunction. Although studies on the effects of CSM have been performed, no chiropractic study has examined regional cerebral metabolism using positron emission tomography (PET). OBJECTIVE: The aim of the present study was to investigate the effects of CSM on brain responses in terms of cerebral glucose metabolic changes measured by [18F]fluorodeoxyglucose positron emission tomography (FDG-PET). METHODS: Twelve male volunteers were recruited. Brain PET scanning was performed twice on each participant, at resting and after CSM. Questionnaires were used for subjective evaluations. A visual analogue scale (VAS) was rated by participants before and after chiropractic treatment, and muscle tone and salivary amylase were measured. RESULTS: Increased glucose metabolism was observed in the inferior prefrontal cortex, anterior cingulated cortex, and middle temporal gyrus, and decreased glucose metabolism was found in the cerebellar vermis and visual association cortex, in the treatment condition (P < .001). Comparisons of questionnaires indicated a lower stress level and better quality of life in the treatment condition. A significantly lower VAS was noted after CSM. Cervical muscle tone and salivary amylase were decreased after CSM. Conclusion The results of this study suggest that CSM affects regional cerebral glucose metabolism related to sympathetic relaxation and pain reduction.

L-type amino acid transporter 1 is associated with chemoresistance in breast cancer via the promotion of amino acid metabolism.

18F-FDG PET/CT has been used as an indicator of chemotherapy effects, but cancer cells can remain even when no FDG uptake is detected, indicating the importance of exploring other metabolomic pathways. Therefore, we explored the amino acid metabolism, including L-type amino acid transporter-1 (LAT1), in breast cancer tissues and clarified the role of LAT1 in therapeutic resistance and clinical outcomes of patients. We evaluated LAT1 expression before and after neoadjuvant chemotherapy and examined the correlation of glucose uptake using FDG-PET with the pathological response of patients. It revealed that LAT1 levels correlated with proliferation after chemotherapy, and amino acid and glucose metabolism were closely correlated. In addition, LAT1 was considered to be involved in treatment resistance and sensitivity only in luminal type breast cancer. Results of in vitro analyses revealed that LAT1 promoted amino acid uptake, which contributed to energy production by supplying amino acids to the TCA cycle. However, in MCF-7 cells treated with chemotherapeutic agents, oncometabolites and branched-chain amino acids also played a pivotal role in energy production and drug resistance, despite decreased glucose metabolism. In conclusion, LAT1 was involved in drug resistance and could be a novel therapeutic target against chemotherapy resistance in luminal type breast cancer.

Brain activation associated with changes in heart rate, heart rate variability, and plasma catecholamines during rectal distention.

OBJECTIVE: To test the hypothesis that gut stimulation provokes autonomic arousal via activation of regional cerebral cortices. How the human brain processes interoceptive signals and forms initial autonomic arousal is one of the key questions to be answered in research on emotion. METHODS: Twelve healthy males participated in this study. A barostat bag was inserted in the rectum and intermittently inflated with 0, 20, or 40 mm Hg at random for 80 seconds. H(2)(15)O positron emission tomography (PET) of the brain, electrocardiography, and blood sampling for catecholamines were performed. Changes in regional cerebral blood flow were interpreted using statistical parametric mapping. RESULTS: Rectal distention with 40 mm Hg induced a significant increase in heart rate, low frequency (LF)/high frequency (HF) ratio of heart rate variability, and plasma adrenaline. Activated brain areas that were associated with increased heart rate during rectal distention were the right insula, right operculum, right dorsolateral prefrontal cortex, putamen, thalamus, periaqueductal gray, and cerebellum (p < .001, uncorrected), whereas those that were associated with an increased LF/HF ratio were the bilateral insula, putamen, thalamus, midbrain, pons, and cerebellum (p < .001, uncorrected). Activated brain areas that were associated with increased plasma adrenaline were the right insula, right orbitofrontal cortex, right parahippocampal gyrus, putamen, thalamus, periaqueductal gray, pons, and cerebellum (p < .001, uncorrected). CONCLUSION: Our results suggest that the right insula and the related body mapping regions may form the functional module of sympathetic arousal in response to gut stimulation.

Evaluation of individual skeletal muscle activity by glucose uptake during pedaling exercise at different workloads using positron emission tomography.

Skeletal muscle glucose uptake closely reflects muscle activity at exercise intensity levels <55% of maximal oxygen consumption (VO2max). Our purpose was to evaluate individual skeletal muscle activity from glucose uptake in humans during pedaling exercise at different workloads by using [18F]fluorodeoxyglucose (FDG) and positron emission tomography (PET). Twenty healthy male subjects were divided into two groups (7 exercise subjects and 13 control subjects). Exercise subjects were studied during 35 min of pedaling exercise at 40 and 55% VO2max exercise intensities. FDG was injected 10 min after the start of exercise or after 20 min of rest. PET scanning of the whole body was conducted after completion of the exercise or rest period. In exercise subjects, mean FDG uptake [standardized uptake ratio (SUR)] of the iliacus muscle and muscles of the anterior part of the thigh was significantly greater than uptake in muscles of control subjects. At 55% VO2max exercise, SURs of the iliacus muscle and thigh muscles, except for the rectus femoris, increased significantly compared with SURs at 40% VO2max exercise. Our results are the first to clarify that the iliacus muscle, as well as the muscles of the anterior thigh, is the prime muscle used during pedaling exercise. In addition, the iliacus muscle and all muscles in the thigh, except for the rectus femoris, contribute when the workload of the pedaling exercise increases from 40 to 55% VO2max.

Application of positron emission tomography to neuroimaging in sports sciences.

To investigate exercise-induced regional metabolic and perfusion changes in the human brain, various methods are available, such as positron emission tomography (PET), functional magnetic resonance imaging (fMRI), near-infrared spectroscopy (NIRS) and electroencephalography (EEG). In this paper, details of methods of metabolic measurement using PET, [(18)F]fluorodeoxyglucose ([(18)F]FDG) and [(15)O]radio-labelled water ([(15)O]H(2)O) will be explained. Functional neuroimaging in the field of neuroscience was started in the 1970s using an autoradiography technique on experimental animals. The first human functional neuroimaging exercise study was conducted in 1987 using a rough measurement system known as (133)Xe inhalation. Although the data was useful, more detailed and exact functional neuroimaging, especially with respect to spatial resolution, was achieved by positron emission tomography. Early studies measured the cerebral blood flow changes during exercise. Recently, PET was made more applicable to exercise physiology and psychology by the use of the tracer [(18)F]FDG. This technique allowed subjects to be scanned after an exercise task is completed but still obtain data from the exercise itself, which is similar to autoradiography studies. In this report, methodological information is provided with respect to the recommended protocol design, the selection of the scanning mode, how to evaluate the cerebral glucose metabolism and how to interpret the regional brain activity using voxel-by-voxel analysis and regions of interest techniques (ROI). Considering the important role of exercise in health promotion, further efforts in this line of research should be encouraged in order to better understand health behavior. Although the number of research papers is still limited, recent work has indicated that the [(18)F]FDG-PET technique is a useful tool to understand brain activity during exercise.

Effects of vitamin C on dark circles of the lower eyelids: quantitative evaluation using image analysis and echogram.

BACKGROUND/AIMS: The pathogenesis of dark circles of the lower eyelid (DCLE) has been considered to involve stasis and hyperpigmentation of the eyelids. We have already reported that dermal thickness of lower eyelid skin may represent another factor that affects the appearance of DCLE. The aim of this study was to evaluate the efficacy of vitamin C, which is known to increase collagen, on DCLE through a clinical trial. METHODS: Fourteen subjects with DCLE applied either 10% sodium ascorbate (ANa) or ascorbic acid glucoside (AG) lotion in split-face fashion (opposite side: vehicle only) for 6 months. Melanin index (MI), erythema index (EI), thickness and echogenicity of the dermis at bilateral lower eyelids was measured during this trial. RESULTS: Change in EI was significantly smaller on the ANa-treated side than on the vehicle-treated side. Dermal thickness tended to be thicker for the ANa-treated side than for the vehicle-treated side, although no significant difference was seen. Both EI and dermal thickness tended to change in parallel manner. On the other hand, no significant differences in changes of EI, MI, and dermal thickness were found between AG- and vehicle-treated sides. CONCLUSION: ANa may improve DCLE by thickening the eyelid dermis and concealing dark coloration due to congested blood.

Melanin and facial skin fluorescence as markers of yellowish discoloration with aging.

BACKGROUND: Although one clinical sign of aging and/or photoaging is a yellowish discoloration of the facial skin, little is known about the cause of this change. In addition to the increase in the epidermal melanin content, it has been suggested that advanced glycation end products (AGEs), which are known to accumulate in photoaged skin, may affect this discoloration. AIM: The objective of this pilot study was to non-invasively investigate the roles of melanin and AGEs in this yellowish discoloration of the facial skin. METHODS: We examined the spectral reflectance at the cheek in 40 healthy Japanese women of various ages (mean age, 38.1 years) using a reflectance spectrophotometer and a spectrofluorimeter. The degree of yellowish tint was evaluated in terms of b(*). The amount of melanin in the skin was evaluated by calculating the melanin index (MI) A(640)-A(670) [A(lambda): log(10) (1/reflectance) at a wavelength of lambda]. The amount of AGEs was roughly evaluated using the AGEs index, which is thought to linearly correlate with the amount of intrinsic fluorescence markers irrespective of the concentration of melanin and is defined as follows: AGEs index=I(5)/SQR (I(1)xI(2)). In this equation, the intensities of reflectance are I(1) at an excitation wavelength of 335 nm, I(2) at an emission wavelength of 390 nm and I(5) at 390 nm under an excitation wavelength of 335 nm. RESULTS: Both b(*) and the AGEs index were significantly correlated with subject age (r=0.34, P<0.05 and r=0.68, P<0.0001, respectively). Significant correlations were also observed between MI and b(*) (r=0.63, P<0.0001) and between the AGEs index and b(*) (r=0.53, P<0.0005). However, no significant correlations were seen between MI and the AGEs index. CONCLUSION: The AGEs index does not appear to be influenced by the amount of melanin and may be utilized as an indicator of the amount of AGEs in the skin. AGEs are likely to play a role in the yellowish discoloration of skin with aging.

Redistribution of whole-body energy metabolism by exercise: a positron emission tomography study.

OBJECTIVE: Our aim was to evaluate changes in glucose metabolism of skeletal muscles and viscera induced by different workloads using (18)F-2-fluoro-2-deoxyglucose ([(18)F]FDG) and three-dimensional positron emission tomography (3-D PET). METHODS: Five male volunteers performed ergometer bicycle exercise for 40 min at 40% and 70% of the maximal O(2) consumption (VO(2max)). [(18)F]FDG was injected 10 min later following the exercise task. Wholebody 3-D PET was performed. Five other male volunteers were studied as a control to compare with the exercise group. The PET image data were analyzed using manually defined regions of interest to quantify the regional metabolic rate of glucose (rMRGlc). Group comparisons were made using analysis of variance, and significant differences (P < 0.05) were determined using Scheffe's test (post hoc analysis). RESULTS: Quantitative analysis demonstrated that rMRGlc increased (P < 0.05) in the skeletal muscles of the thigh at mild or moderate workloads when compared with the resting controls. For visceral organs such as the liver and brain, metabolic reduction was significant (P < 0.05) at mild and/or moderate exercise workload. CONCLUSIONS: The present study demonstrated linear increases or decreases in glucose uptake by skeletal muscles and viscera with mild and moderate exercise workloads, suggesting the presence of homeostatic energy metabolism. This result supports the finding that [(18)F]FDG-PET can be used as an index of organ energy metabolism for moderate exercise workloads (70% VO(2max)). The results of this investigation may contribute to sports medicine and rehabilitation science.

Diagnostic Accuracy of Positron Emission Mammography with 18F-fluorodeoxyglucose in Breast Cancer Tumor of Less than 20 mm in Size.

OBJECTIVES: To investigate the diagnostic accuracy of positron emission mammography (PEM) and positron emission tomography/computed tomography (PET/CT) for small breast tumors of less than 20 mm in size. METHODS: The study was conducted on a total of 100 subjects (i.e., 50 patients with pathologically proven breast cancer and 50 normal cases of medical screening). The total number of tumors was 54 (mean size: 11±5.1 mm, range: 4-20 mm). The diagnostic accuracy of PEM alone, PET/CT alone, and combined PET/CT and PEM was evaluated by two nuclear medicine physicians based on visual inspection. The two groups (i.e., tumors of ≤ 10 mm and > 10-20 mm) were compared in terms of the diagnostic capability of the three modalities (PEM alone, PET/CT alone, and PET/CT+PEM). RESULTS: The sensitivities of PEM alone, PET/CT alone, and combined PET/CT and PEM were 72%, 60%, and 76%, respectively. The specificities of these tests were 98%, 100%, and 98%, respectively. Furthermore, the accuracies of these diagnostic modalities were 85%, 79%, and 87%, respectively. The combined PET/CT and PEM showed significantly higher sensitivity and accuracy than PET/CT alone (P=0.005 and P=0.02, respectively). In addition, PEM demonstrated a significantly higher sensitivity than PET/CT in the ≤ 10 mm group (P=0.03); however, no difference was observed between the two modalities in the > 10 mm group in terms of sensitivity. CONCLUSION: 18F-fluorodeoxyglucose PET had limited capability for the detection of small breast cancers of < 10 mm. Combined PET/CT and PEM showed higher sensitivity and accuracy, compared to PET/CT alone.

Brain histamine H1 receptor occupancy of orally administered antihistamines, bepotastine and diphenhydramine, measured by PET with 11C-doxepin.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: 'Bepotastine besilate' is a novel second-generation antihistamine developed in Japan and its antiallergic effects have already been demonstrated by various studies. However, only a few clinical studies regarding its sedative property are available. In addition, histamine H(1) receptor occupancy (H(1)RO) of this new antihistamine has never been measured by positron emission tomography (PET). WHAT THIS STUDY ADDS: This paper provides the first measurement result of cerebral H(1)RO of bepotastine besilate (approximately 15%) as determined by PET. This result is in accordance with the clinical classification of bepotastine as a second-generation antihistamine. In addition, the relationship between subjective sleepiness and cerebral H(1)RO of this second-generation antihistamine is demonstrated for the first time using a placebo-controlled crossover study design. AIMS Antihistamines are frequently used for treating various allergic diseases, but often induce sedation. The degree of sedation can be evaluated by measuring histamine H(1) receptor occupancy (H(1)RO) in the brain using positron emission tomography (PET). The aim was to measure H(1)RO of bepotastine, a new second-generation antihistamine, and to compare it with that of diphenhydramine. METHODS: Eight healthy male volunteers (mean age +/- SD 24.4 +/- 3.3 years) were studied after single oral administration of bepotastine (10 mg), diphenhydramine (30 mg) or placebo, by PET imaging with (11)C-doxepin in a crossover study design. Binding potential ratio and H(1)ROs were calculated using placebo data and were compared between bepotastine and diphenhydramine in the anterior and posterior cingulate gyri (ACG and PCG, respectively), superior and inferior frontal cortices (SFC and IFC, respectively), orbitofrontal cortex (OFC), insular cortex (IC), lateral and medial temporal cortices (LTC and MTC, respectively), parietal cortex (PC), occipital cortex (OC) and sensorimotor cortex (SMC). Plasma concentration of each antihistamine was measured, and its correlation to H(1)RO was examined. RESULTS: H(1)RO after bepotastine treatment was significantly lower than that after diphenhydramine treatment in all cortical regions (P < 0.001). Mean H(1)ROs of bepotastine and diphenhydramine were 14.7% and 56.4%, respectively. H(1)ROs of both bepotastine and diphenhydramine correlated to their respective drug plasma concentration (P < 0.001). CONCLUSION: Oral bepotastine (10 mg), with its relatively low H(1)RO and thus minimal sedation, has the potential for use as a mildly or slightly sedative antihistamine in the treatment of various allergic disorders.

Effects of a sedative antihistamine, D-chlorpheniramine, on regional cerebral perfusion and performance during simulated car driving.

OBJECTIVES: The sedative side effects of antihistamines have been recognized to be potentially dangerous in car driving, but the mechanism underlying these effects has not yet been elucidated to date. The aim of the present study is to examine regional cerebral blood flow (rCBF) responses during a simulated car-driving task following oral administration of D-chlorpheniramine using positron emission tomography (PET) and [15O]H2O, based on a single-blind cross-over study-design. METHODS: Right-handed, healthy male volunteers (n = 14) drove a car in a simulated environment following oral administration of D-chlorpheniramine repetab 6 mg or placebo. Their rCBF was measured using PET with [15O]H2O in the following three conditions: (1) resting, (2) active driving, and (3) passive driving. All 'in-car' views during the simulated driving were videotaped and used for rating driving performance. RESULTS: Performance evaluation revealed that the number of lane deviations significantly increased in the D-chlorpheniramine condition compared with the placebo condition (p < 0.01). Subjective sleepiness was not significantly different between the two drug conditions. The regions of diminished brain responses following D-chlorpheniramine treatment were detected in the parietal, temporal and visual cortices, and in the cerebellum. The regions of augmented rCBF responses were found in the orbitofrontal cortex and cerebellar vermis. CONCLUSION: These results suggest that D-chlorpheniramine tends to suppress visuo-spatial cognition and visuo-motor coordinating functions rather than attention and motor functions during car driving.

Bone metabolic activity around dental implants under loading observed using bone scintigraphy.

PURPOSE: The purpose of this study was to determine dynamic changes in bone metabolism around osseointegrated titanium implants under mechanical stress. MATERIALS AND METHODS: Two titanium implants were inserted parallel to each other in the tibiae of rats and perpendicular to the bone surface with the superior aspect of the implant exposed. Eight weeks after insertion, closed coil springs with 0.5, 1.0, 2.0, and 4.0 N were applied to the exposed superior portion of the implant for 7 weeks to apply a continuous mechanical stress. Bone scintigrams were performed using a gamma camera with a modified high-resolution pinhole collimator. Images were made at 1, 4, 7, 10, 14, 21, 28, 49, and 56 days after insertion and at 3 days and at weekly intervals until 7 weeks after load application. The ratio of the metabolic activity around the implants to that around a reference site (uptake ratio) was established. The Friedman, Steel, and Tukey tests (P < .05) were used to assess statistical significance. RESULTS: In the process of osseointegration, the uptake ratio increased during the first week after implant insertion and then gradually decreased. During the initial 3 weeks the uptake ratio was significantly higher than at 1 day after insertion. In the process of load application, the uptake ratio increased with 2.0- and 4.0-N loads; it was significantly higher until 6 weeks than it had been before load application. CONCLUSIONS: Bone metabolism around the implants increases with loading and depends on the magnitude and period of the loading.