ACTIVITY CONCENTRATIONS OF RADIOCAESIUM, 90SR AND 129I IN AGRICULTURAL CROPS COLLECTED FROM FUKUSHIMA AND REFERENCE AREAS IN JAPAN, AND INTERNAL RADIATION DOSES.

Significant quantities of radionuclides were released into the environment due to the 2011 TEPCO's FDNPS accident. Radiocaesium is the most important radionuclide for assessment of radiation dose, and small amounts of 90Sr and very long-lived radionuclide of 129I were also released into the environment. Spinach, potato and brown rice were collected from Fukushima, neighboring prefectures and reference areas of negligible deposition in 2018 and 2019. The activity concentration of 137Cs in crops in Hamadori (coastal side) was relatively higher than other areas. The activity concentration of 90Sr in the crops showed a similar range among four areas in Fukushima, and they were similar level of those collected throughout Japan. The activity concentration of 129I in the crops collected from Hamadori was higher than other Fukushima areas. However, the activity ratio of 129I/137Cs was lower by five to seven orders of magnitude. Internal radiation doses of radiocaesium for adult males from ingestion of local crops collected from Hamadori were 0.0046 mSv, and that of 129I were 0.00000045 mSv in 2019.

Development of In Vitro Endothelialised Stents - Review.

Endovascular treatment is prevalent as a primary treatment for coronary and peripheral arterial diseases. Although the introduction of drug-eluting stents (DES) dramatically reduced the risk of in-stent restenosis, stent thrombosis persists as an issue. Notwithstanding improvements in newer generation DES, they are yet to address the urgent clinical need to abolish the late stent complications that result from in-stent restenosis and are associated with late thrombus formation. These often lead to acute coronary syndromes with high mortality in coronary artery disease and acute limb ischemia with a high risk of limb amputation in peripheral arterial disease. Recently, a significant amount of research has focused on alternative solutions to improve stent biocompatibility by using tissue engineering. There are two types of tissue engineering endothelialisation methods: in vitro and in vivo. To date, commercially available in vivo endothelialised stents have failed to demonstrate antithrombotic or anti-stenosis efficacy in clinical trials. In contrast, the in vitro endothelialisation methods exhibit the advantage of monitoring cell type and growth prior to implantation, enabling better quality control. The present review discusses tissue-engineered candidate stents constructed by distinct in vitro endothelialisation approaches, with a particular focus on fabrication processes, including cell source selection, stent material composition, stent surface modifications, efficacy and safety evidence from in vitro and in vivo studies, and future directions.

Radiocaesium in the environment of Fukushima.

It has been 10 years since the accident at Fukushima Daiichi nuclear power plant in 2011. Large quantities of 131I, 134Cs, and 137Cs were released into the environment, and 80% of 137Cs still remains. In addition to the decrease by attenuation, the transfer of 137Cs to plants, animals, and humans is decreasing due to movement and changing fractions with elapsed time. The activity concentration of 137Cs in the atmosphere has decreased drastically, and the internal radiation dose due to inhalation is negligible. The activity concentration of 137Cs in agricultural plants is decreasing due to decontamination of soil, application of potassium, and lower levels in irrigation water. The activity concentration of 137Cs in wild animals is decreasing, and shows seasonal variation in wild boars. The activity concentration of 137Cs in offshore seawater has decreased to 0.01 Bq l-1. Therefore, the radiation dose is <1 mSv of the additional radiation dose.

Stimulatory effect of insulin on H+-ATPase in the proximal tubule via the Akt/mTORC2 pathway.

PURPOSE: Acid-base transport in renal proximal tubules (PTs) is mainly sodium-dependent and conducted in coordination by the apical Na+/H+ exchanger (NHE3), vacuolar H+-adenosine triphosphatase (V-ATPase), and the basolateral Na+/HCO3- cotransporter. V-ATPase on PTs is well-known to play an important role in proton excretion. Recently we reported a stimulatory effect of insulin on these transporters. However, it is unclear whether insulin is involved in acid-base balance in PTs. Thus, we assessed the role of insulin in acid-base balance in PTs. METHODS: V-ATPase activity was evaluated using freshly isolated PTs obtained from mice, and specific inhibitors were then used to assess the signaling pathways involved in the observed effects. RESULTS: V-ATPase activity in PTs was markedly enhanced by insulin, and its activation was completely inhibited by bafilomycin (a V-ATPase-specific inhibitor), Akt inhibitor VIII, and PP242 (an mTORC1/2 inhibitor), but not by rapamycin (an mTORC1 inhibitor). V-ATPase activity was stimulated by 1 nm insulin by approximately 20% above baseline, which was completely suppressed by Akt1/2 inhibitor VIII. PP242 completely suppressed the insulin-mediated V-ATPase stimulation in mouse PTs, whereas rapamycin failed to influence the effect of insulin. Insulin-induced Akt phosphorylation in the mouse renal cortex was completely suppressed by Akt1/2 inhibitor VIII and PP242, but not by rapamycin. CONCLUSION: Our results indicate that stimulation of V-ATPase activity by insulin in PTs is mediated via the Akt2/mTORC2 pathway. These results reveal the mechanism underlying the complex signaling in PT acid-base balance, providing treatment targets for renal disease.

SPECIATION OF IODINE IN SOIL SOLUTION IN FOREST AND GRASSLAND SOILS IN ROKKASHO, JAPAN.

The behaviour of I in soil depends on its chemical form in soil solution. Stable I (127I) in the soil solution under actual soil conditions was investigated as a natural analogue of long-lived radioiodine (129I). Soil samples were collected at 5-cm depth intervals down to 20 cm from forests and grasslands in Rokkasho, where the Japanese first commercial nuclear fuel reprocessing plant is located, and the soil solution was extracted by centrifugation. Almost half of total I in the soil solution was iodide, and the other half was dissolved organic I (DOI), with iodate under the detection limit. The proportion of DOI in total I at 0-5 cm depth was larger than the proportions at 5-20 cm depth. The concentration of DOI was positively correlated with that of DOC in the soil solution, suggesting that the behaviour of DOI in the surface soil is affected by labile organic matter dynamics.

Changes in the chemical form of exogenous iodine in forest soils and their extracts.

Information about the chemical form of exogenous iodine in soil is important for predicting the mobility and behaviour of radioiodine in the terrestrial environment. In this study, soil samples collected at various depths in a pine forest in Rokkasho, Japan, were spiked with stable iodine (as iodide or iodate); after incubation of the spiked soils for 1 or 14 d, the chemical forms of iodine were investigated in both the soils and their water extracts. In surface soil and its extracts, inorganic iodine was found to have been transformed to organically bound forms after incubation for 14 d, resulting in a decrease in the amount of water-extractable iodine in the soil. In contrast, in subsurface soil, which had low organic matter content, the predominant chemical form of iodine after incubation did not differ from that in the spiked soil, and the amount of water-extractable iodine did not decrease noticeably.

Nanogel-based pneumococcal surface protein A nasal vaccine induces microRNA-associated Th17 cell responses with neutralizing antibodies against Streptococcus pneumoniae in macaques.

We previously established a nanosized nasal vaccine delivery system by using a cationic cholesteryl group-bearing pullulan nanogel (cCHP nanogel), which is a universal protein-based antigen-delivery vehicle for adjuvant-free nasal vaccination. In the present study, we examined the central nervous system safety and efficacy of nasal vaccination with our developed cCHP nanogel containing pneumococcal surface protein A (PspA-nanogel) against pneumococcal infection in nonhuman primates. When [(18)F]-labeled PspA-nanogel was nasally administered to a rhesus macaque (Macaca mulatta), longer-term retention of PspA was noted in the nasal cavity when compared with administration of PspA alone. Of importance, no deposition of [(18)F]-PspA was seen in the olfactory bulbs or brain. Nasal PspA-nanogel vaccination effectively induced PspA-specific serum IgG with protective activity and mucosal secretory IgA (SIgA) Ab responses in cynomolgus macaques (Macaca fascicularis). Nasal PspA-nanogel-induced immune responses were mediated through T-helper (Th) 2 and Th17 cytokine responses concomitantly with marked increases in the levels of miR-181a and miR-326 in the serum and respiratory tract tissues, respectively, of the macaques. These results demonstrate that nasal PspA-nanogel vaccination is a safe and effective strategy for the development of a nasal vaccine for the prevention of pneumonia in humans.

Radiocesium and radioiodine in soil particles agitated by agricultural practices: field observation after the Fukushima nuclear accident.

Three weeks after the accident at the Fukushima Daiichi Nuclear Power Plant, we determined the activity concentrations of (131)I, (134)Cs and (137)Cs in atmospheric dust fugitively resuspended from soil particles due to soil surface perturbation by agricultural practices. The atmospheric concentrations of (131)I, (134)Cs and (137)Cs increased because of the agitation of soil particles by a hammer-knife mower and a rotary tiller. Coarse soil particles were primarily agitated by the perturbation of the soil surface of Andosols. For dust particles smaller than 10 µm, the resuspension factors of radiocesium during the operation of agricultural equipment were 16-times higher than those under background condition. Before tillage, most of the radionuclides accumulated within a few cm of the soil surface. Tillage diluted their concentration in the uppermost soil layer.

Early recurrence after surgical resection in patients with pathological stage I non-small cell lung cancer.

INTRODUCTION: Early recurrence is observed even in patients who undergo complete resection and had pathological (p-) stage I. Therefore, we focused on early recurrence, and attempted to elucidate the relationship between early recurrence and clinicopathological factors. METHODS: Between May 1993 and December 2005, 1201 patients with non-small cell lung cancer (NSCLC) underwent surgical treatment at our institution. Of these, 402 patients who underwent complete resection and had p-stage I NSCLC were retrospectively analyzed for clinicopathological factors. Patients were divided into four groups according to the period between surgery and recurrence (R): no recurrence (NR, n = 331), late recurrence (LR, n = 28, R > 2 years), intermediate recurrence (IR, n = 22, 1 year < R < or = 2 years), and early recurrence (ER, n = 21, R < or = 1 year). RESULTS: The overall 5-year survival rate for patients with p-stage I was 79.9 %. The overall 5-year survival rates were 91.0 %, 55.6 %, 17.1 %, and 7.5 % for the NR, LR, IR, and ER group, respectively. Preoperative high CEA level, lymphatic permeation, and pleural invasion were proven to be independent factors for overall recurrence. Moreover, multivariate analysis showed that preoperative CEA level, pathological T factor, lymphatic permeation, vascular invasion, and pleural invasion influenced early recurrence within one year. CONCLUSIONS: The present study demonstrated that preoperative CEA level, pathological T-factor, lymphatic permeation, vascular invasion, and pleural invasion were independent prognostic factors for early recurrence within one year, even in patients with pathological stage I. In patients with these factors, adjuvant therapy may be indicated since this may improve their survival.

Nationwide surveillance of bacterial respiratory pathogens conducted by the Japanese Society of Chemotherapy in 2007: general view of the pathogens' antibacterial susceptibility.

For the purpose of a nationwide surveillance of the antimicrobial susceptibility of bacterial respiratory pathogens in patients in Japan, the Japanese Society of Chemotherapy conducted their second year survey, during the period from January to August, 2007. A total of 1178 strains were collected from clinical specimens obtained from adult patients with well-diagnosed respiratory tract infections. Susceptibility testing was evaluable for 1108 strains (226 Staphylococcus aureus, 257 Streptococcus pneumoniae, 6 Streptococcus pyogenes, 206 Haemophilus influenzae, 120 Moraxella catarrhalis, 122 Klebsiella pneumoniae, and 171 Pseudomonas aeruginosa). A total of 44 antibacterial agents, including 26 beta-lactams (four penicillins, three penicillins in combination with beta-lactamase inhibitors, four oral cephems, eight parenteral cephems, one monobactam, five carbapenems, and one penem), three aminoglycosides, four macrolides (including ketolide), one lincosamide, one tetracycline, two glycopeptides, six fluoroquinolones, and one oxazolidinone were used for the study. Analysis was conducted at the central reference laboratory according to the method recommended by the Clinical and Laboratory Standards Institute (CLSI). The incidence of methicillinresistant Staphylococcus aureus (MRSA) was high, at 59.7%, and the incidences of penicillin-intermediateresistant and -resistant Streptococcus pneumoniae (PISP and PRSP) were 30.4% and 5.1%, respectively. Among Haemophilus influenzae strains, 19.9% of them were found to be beta-lactamase-non-producing ampicillin (ABPC)-intermediately-resistant (BLNAI), 29.1% to be beta-lactamasenon-producing ABPC-resistant (BLNAR), and 6.7% to be beta-lactamase-producing ABPC-resistant (BLPAR) strains. Extended-spectrum beta-lactamase-producing Klebsiella pneumoniae was not isolated. Two isolates (1.2%) of Pseudomonas aeruginosa were found to be metallo-beta-lactamase-producing strains, including one (0.6%) suspected multidrug-resistant strain showing resistance to imipenem, amikacin, and ciprofloxacin. These data will be a useful reference for future periodic surveillance studies and for investigations to control resistant infections as well. Continued surveillance is required to prevent the further spread of these antimicrobial resistances.

Morbidity in video-assisted thoracoscopic lobectomy for clinical stage I non-small cell lung cancer: is VATS lobectomy really safe?

OBJECTIVE: The objective of this study was to compare video-assisted thoracoscopic lobectomy (VATS lobectomy) with standard thoracotomy in terms of morbidity and mortality. PATIENTS AND METHODS: Two-hundred and forty-nine consecutive patients with clinical (c) stage I non-small cell lung cancer who underwent surgery between 1999 and 2003 were retrospectively analyzed. All of the patients underwent surgical resection that was at least as extensive as lobectomy. VATS lobectomy was performed in 73 patients, and thoracotomy in 176 patients. RESULTS: The clinical stages were stage IA in 151 (60.6 %), and stage IB in 98 (39.4 %), and the pathological stages were I in 206 (82.7 %), II in 16 (6.4 %), and III in 27 (10.9 %). The mean operation time was 291 minutes for VATS and 215 minutes for thoracotomy ( P = 0.0 042). The mean blood loss was 160 ml and 191 ml ( P = 0.2 738), respectively. Mortality was 1.4 % (1/73) in the VATS group, and 2.3 % (4/176) in the thoracotomy group ( P = 0.6 438). Morbidity was 19.2 % (14/73), and 24.4 % (44/176), respectively ( P = 0.1 315). Air leakage was the most frequent complication. Anastomotic leakage was found in four patients who underwent thoracotomy. The incidence of pulmonary vessel injury was 8.2 % in the VATS group and 1.7 % in the thoracotomy group ( P = 0.0 361). While pulmonary vessel injury was observed frequently in the intermediate part of the study period, the incidence decreased in the late period. CONCLUSIONS: Pulmonary vessel injury, longer operation times, and greater blood loss have been frequently observed with VATS lobectomy. Proficiency is required to perform VATS lobectomy, and the procedure should be performed by a well-trained surgeon as indicated by the results of this study.

[Surgical outcome of tracheobronchial reconstruction for lung cancer].

We retrospectively evaluated the surgical outcome after sleeve lobectomy and pneumonectomy with tracheobronchial reconstruction for lung cancer. From 1993 to 2008, 46 patients with primary lung cancer underwent these surgical procedures. Seventeen patients (37%) received induction therapy, 15 received chemotherapy, while chemoradiotherapy or radiotherapy alone were received by one patient each. Sleeve lobectomy without carinal resection was performed in 41 patients. Carinal resection with 2 sleeve pneumonectomies was performed in 5 patients. There were no operative deaths. Bronchopleural fistula occurred in one patient, who required completion pneumonectomy. One patient presented local mucosal necrosis in the anastomotic site and was managed conservatively. Two patients had bronchial strictures as late complications and successfully dilated by a balloon using bronchoscopy. Overall 5-year and 10-year survival rates were 54% and 48%, respectively. No recurrence developed at any anastomotic site. The results showed that sleeve lobectomy and pneumonectomy with tracheobronchial reconstruction can be performed with low mortality and bronchial anastomotic complication rates. As well, local control of the tumor was satisfactory.

The first nationwide surveillance of bacterial respiratory pathogens conducted by the Japanese Society of Chemotherapy. Part 1: a general view of antibacterial susceptibility.

The Japanese Society of Chemotherapy (JSC) conducted the first nationwide surveillance of bacterial respiratory pathogens during the period from January to August 2006. With the cooperation of 32 medical institutions throughout Japan, a total of 924 strains belonging to seven clinically relevant bacterial species were collected from adult patients with well-diagnosed respiratory tract infections (RTIs). Antimicrobial susceptibility testing of the 887 evaluable strains (205 Staphylococcus aureus, 200 Streptococcus pneumoniae, 9 Streptococcus pyogenes, 165 Haemophilus influenzae, 91 Moraxella catarrhalis, 74 Klebsiella pneumoniae, and 143 Pseudomonas aeruginosa) to 42 antibacterial agents was conducted at the Central Laboratory of the Research Center for Anti-infective Drugs of the Kitasato Institute, according to recommendations issued by the Clinical and Laboratory Standards Institute (CLSI). The antibacterial agents employed were 25 beta-lactams, three aminoglycosides, four macrolides (including one azalide and one ketolide), one lincosamide, one tetracycline, two glycopeptides, five fluoroquinolones, and one oxazolidinone. The incidence of methicillin-resistant S. aureus (MRSA) was 63.4%, and the incidences of penicillin-intermediately resistant S. pneumoniae (PISP) and penicillin-resistant S. pneumoniae (PRSP) were 35.0% and 4.0%, respectively. Among H. influenzae, 21.2% of the strains were found to be beta-lactamase-nonproducing ampicillin (ABPC)-intermediately resistant (BLNAI), 29.1% to be beta-lactamase-nonproducing ABPC-resistant (BLNAR), and 4.8% to be beta-lactamaseproducing ABPC-resistant (BLPAR) strains. The incidence of extended-spectrum beta-lactamase-producing K. pneumoniae was 2.7% (2 of 74 strains). Three (2.1%) of the 143 P. aeruginosa strains were found to be metallo-beta-lactamaseproducing, including 1 (0.7%) multidrug-resistant strain. Through the nationwide surveillance, we obtained fundamental antimicrobial susceptibility data of clinically relevant bacterial pathogens in adult RTI to various antibacterial agents. These data will be a useful reference for future periodic surveillance studies, as well as for investigations to control antimicrobial-resistant pathogens.

Domain-related differentiation of working memory in the Japanese macaque (Macaca fuscata) frontal cortex: a positron emission tomography study.

The lateral prefrontal cortex (LPFC) is important for working memory (WM) task performance. Neuropsychological and neurophysiological studies in monkeys suggest that the lateral prefrontal cortex is functionally segregated based on the working memory domain (spatial vs. non-spatial). However, this is not supported by most human neuroimaging studies, and the discrepancy might be due to differences in methods and/or species (monkey neuropsychology/physiology vs. human neuroimaging). We used positron emission topography to examine the functional segregation of the lateral prefrontal cortex of Japanese macaques (Macaca fuscata) that showed near 100% accuracy on spatial and non-spatial working memory tasks. Compared with activity during the non-working memory control tasks, the dorsolateral prefrontal cortex (DLPFC) was more active during the non-spatial, but not during the spatial, working memory task, although a muscimol microinjection into the dorsolateral prefrontal cortex significantly impaired the performance of both working memory tasks. A direct comparison of the brain activity between the two working memory tasks revealed no differences within the lateral prefrontal cortex, whereas the premotor area was more active during the spatial working memory task. Comparing the delay-specific activity, which did not include task-associated stimulus/response-related activity, revealed more spatial working memory-related activity in the posterior parietal and premotor areas, and more non-spatial working memory-related activity in the dorsolateral prefrontal cortex and hippocampus. These results suggest that working memory in the monkey brain is segregated based on domain, not within the lateral prefrontal cortex but rather between the posterior parietal-premotor areas and the dorsolateral prefrontal-hippocampus areas.

F-18 fluorodeoxyglucose uptake in leiomyomatous uterus.

Leiomyomas of uterus are common disease in gynecology. It is important to differentiate leiomyoma from leiomyosarcoma at the decision of treatment methods, especially in the case of the conservative treatment for uterine leiomyoma. But the exact diagnosis of benign leiomyoma is often difficult due to the degeneration of myoma by imaging modalities including magnetic resonance imaging. Recently, whole-body positron emission tomography (PET) using F-18 fluorodeoxyglucose (FDG) has been used for a diagnosis of malignant tumors. There is a growing body of evidence for the use of FDG in differentiating malignant from benign disease. But optimal utilization in gynecology remains unclear. Our case represents increased uptake of FDG in myomatous uterus, which is pathologically confirmed benign leiomyoma by the hysterectomy. Immunohistochemical analysis of glucose transporter-1 showed positive in endometrial tissue and negative in leiomyoma. Our case indicates that myomatous uterus in premenopausal women shows the potential pitfall of a positive result of FDG-PET.

Whole-body positron emission tomography with F-18 fluorodeoxyglucose for the detection of recurrence in uterine sarcomas.

We evaluated the usefulness of whole-body positron emission tomography (PET) using F-18 fluorodeoxyglucose (FDG-PET) for the detection of recurrence in follow-up patients after primary treatment of uterine sarcoma. Eight patients with pathologically proven uterine sarcoma underwent FDG-PET, computed tomography (CT), and ultrasonography (US). Final diagnoses of recurrence were established in five cases (three carcinosarcomas and two leiomyosarcomas). PET revealed recurrent sites in the intraperitoneum, liver, lung, bone, and retroperitoneal lymph nodes. However, the minimum size of the tumor detected by PET depended on the sites of recurrence. CT and US images showed two false-negative cases of intraperitoneal tumors. PET was able to detect a solitary small intraperitoneal tumor, which was very difficult to detect by CT and US. Positive PET findings did not affect the prognosis in three of the five recurrent patients; however, the remaining two patients consequently underwent the combination therapy consisting of surgery and chemotherapy and survived for more than 1 year after the positive FDG-PET results. Application of PET imaging for the early detection of recurrent sites was useful for the decision of treatment strategy for patients with recurrent uterine sarcoma.

Whole-body positron emission tomography and tumor marker CA125 for detection of recurrence in epithelial ovarian cancer.

We evaluated the clinical role of the combination of positron emission tomography (PET) with F-18 fluorodeoxyglucose (FDG) and tumor marker CA125, in the detection of recurrence after initial therapy for epithelial ovarian cancer. The indication is the cases that cannot be confirmed the recurrence by conventional imaging modalities. Ninety patients underwent PET and computed tomography, including the measurement of specific tumor markers. FDG-PET confirmed recurrence in 46 patients (51%), and the recurrent site was confirmed by PET alone in 17 (37%). PET had high sensitivity for detecting both intraperitoneal and retroperitoneal metastases (93.9 and 92.9%, respectively). PET imaging was able to detect normal-sized metastases in the lymph nodes in 14 (50%) of the 28 patients with retroperitoneal metastasis. PET could show 87.5% positive rate of recurrent patients with asymptomatic rise of CA125 who had no sign of recurrence by conventional imaging methods. Of the 46 recurrent patients, 41 (89%) had specific elevated titers of CA125 at the first treatment. PET imaging was able to detect recurrence at relatively low titers (a median 68 U/mL) of CA125. In 8 (19.5%) of these 41 patients, recurrence with normal CA125 levels could be confirmed only by PET. The sensitivity of the combination of PET and CA125 was 97.8% with only one false-negative case. The combination of FDG-PET and CA125 titer is useful for the accurate detection of recurrence.

Evaluation of [18F]fluorinated sigma receptor ligands in the conscious monkey brain.

PET-imaging of the sigma receptors is very helpful to understand processes, e.g., several central nervous system (CNS)-diseases in which the sigma receptors are involved. The [(18)F]fluoroethylated analogs of SA4503 and SA5845 ([(18)F]FE-SA4503 and [(18)F]FE-SA5845) were evaluated in conscious monkeys to estimate its suitability for human application for PET. Conscious monkeys (Macaca Mulatta) were either scanned with [(18)F]FE-SA4503 or [(18)F]FE-SA5845 (n = 3 for both groups, 220-802 MBq). After a dynamic study of 120 min, radioactivity was displaced by intravenous (i.v.) injection of haloperidol (1 mg/kg). One month later the same set of three monkeys were scanned with [(18)F]FE-SA4503 for 120 min and "cold" SA4503 (1 mg/kg) was infused to displace the radioactivity, and the other three monkeys were pretreated with haloperidol (1 mg/kg) before the 120-min PET-scan with [(18)F]FE-SA5845. Cortical areas (cingulate, frontal, occipital, parietal, temporal), striatum, and thalamus showed high radioactivity uptake. Infusion of haloperidol displaced the radioactivity levels of the two radioligands. The same effect was found for [(18)F]FE-SA4503 after SA4503 displacement. Pretreatment with haloperidol blocked the [(18)F]FE-SA5845 binding to give PET-images with low and uniform uptake in the brain. The findings demonstrated the reversible binding of the two radioligands. Metabolite analysis showed that 14% and 23% parent compound of [(18)F]FE-SA5845 and [(18)F]FE-SA4503, respectively, at 120 min postinjection was present in plasma. Kinetic analysis showed that the binding potential of [(18)F]FE-SA5845 was higher in all brain regions than that of [(18)F]FE-SA4503 (4.75-8.79 vs. 1.65-4.04). The highest binding potential was found in the hippocampus, followed by the cortical regions, thalamus, cerebellar hemisphere, striatum and vermis. Both [(18)F]FE-SA compounds bound specifically to cerebral sigma receptors of the monkey and have potential for mapping sigma receptors in the human brain.