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H Tsukada

Publications and source records attributed to H Tsukada.

At least 19 recordsLinked to original sources
PubMed2004

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.

Animals↗
PubMed2004

[Clinicopathologic features of small-sized peripheral lung cancer; is intentional limited resection appropriate for selected patients?].

We sought to determine the eligibility of patients with early peripheral lung cancer for intentional limited resection. The clinicopathologic features of 103 patients who underwent lobectomy and mediastinal nodal dissection for early stage peripheral lung cancer measuring 2 cm or less in maximum dimension between 1992 and 2002 were examined retrospectively. The lymph node metastasis and residual cancer after thoracoscopic partial resection were analyzed by the following categories. Three groups were divided by maximum dimension of the primary lesion in the resected specimen; 10 mm or less (n = 11), 15 mm or less (n = 33), and 20 mm or less (n = 59). Two groups were divided by lesion histology; bronchioloalveolar adenocarcinoma (BAC) [n = 42] and invasive lung cancer (n = 61). Residual cancer was found in the residual lobe after thoracoscopic partial resection in 3 of 43 patients who had no diagnosis preoperatively. Their maximum dimensions were 15 mm or less. No lymph node metastasis was detected in the patients with tumor measuring 10 mm or less, and BAC. Intentional limited resection without mediastinal nodal dissection is appropriate for patients with tumor measuring 10 mm or less and BAC. Further investigation associated with partial resection is necessary.

Adenocarcinoma, Bronchiolo-Alveolar↗
PubMed2003

Effects of an aldose reductase inhibitor on gastroenteropathy in streptozotocin-diabetic rats.

We investigated the effects of epalrestat, an aldose reductase inhibitor (ARI), on gastric emptying, fecal water content, and electrolyte transport in distal colon in streptozotocin (STZ)-induced diabetic rats. We measured gastric emptying time by acetaminophen method and short-circuit-current (Isc) in colonic mucosa using an Ussing chamber. The Isc in response to electric-field-stimulation (EFS) was decreased in untreated rats due to suppression by Cl- secretion. ARI treatment alleviated this suppression (2.7 +/- 0.6 vs. 7.4 +/- 1.1 microA/0.38 cm2 at 8 weeks after treatment, 1.1 +/- 0.2 vs. 7.0 +/- 1.0 at 12 weeks after treatment, P<0.05). In addition, the percentage of fecal water content in untreated rats was significantly lower than in ARI-treated rats (58.0 +/- 2.0 vs. 67.6 +/- 0.8% at 8 weeks, 56.9 +/- 2.1 vs. 63.4 +/- 1.4 at 12 weeks, P<0.05). From STZ injection to 8 weeks, the serum levels of acetaminophen in the diabetic rats were significantly lower than in controls, indicating delayed gastric emptying. At 12 weeks in the diabetic rats treated with ARI, the serum levels of acetaminophen were significantly higher than in the untreated diabetic rats (6.6 +/- 0.4 vs. 3.5 +/- 0.5 microg/ml, P<0.05). ARI-treatment ameliorated delayed gastric emptying without improving glycemic control. These findings show that ARI partially prevented progression of impaired gastric emptying, ion transport, and water transport, and suggest that epalrestat might be useful in the treatment of diabetic gastroenteropathy.

Acetaminophen↗
PubMed2002

Synthesis and evaluation of [18F]fluoroethyl SA4503 as a PET ligand for the sigma receptor.

The sigma receptor might be involved in several diseases in the central nervous system. It occurs in the endocrine, immune, and other peripheral organ systems and is expressed in a variety of human tumors. The [18F]fluoroethyl analog of the sigma1-selective ligand SA4503 ([18F]FE-SA4503) was prepared and evaluated in animals to investigate its suitability for in vivo measurement of sigma receptors with positron emission tomography (PET). [18F]FE-SA4503 was synthesized by [18F]fluoroethylation of the corresponding O-demethyl precursor in an overall radiochemical yield of 4-7% (EOB) with a specific activity of >100 TBq/mmol. The radioligand had higher in vitro affinity for the sigma receptor than SA4503 (IC(50) sigma1 6.48 nM, IC50 sigma2 2.11 nM). [18F]FE-SA4503 was injected into mice. Uptake could be blocked by co-injection of the sigma receptor ligands haloperidol, pentazocine, and cold SA4503, but not with other receptor ligands. Ex vivo autoradiography studies in rats showed regional distribution in the brain similar to [11C]SA4503. Hippocampus, thalamus, and cortical areas were clearly delineated by [18F]FE-SA4503. The uptake was blocked by SA4503 treatment. In the rat brain, only a small portion of metabolites (6.6% of brain radioactivity) was detected at 30 min postinjection, whereas in plasma the fraction of metabolites amounted to 51.3% of plasma radioactivity. The kinetics of [18F]FE-SA4503 was measured with PET in the conscious monkey brain. High uptake values were found in the cortex, thalamus, cerebellum, and striatum, reaching a plateau value at 30 min postinjection. It is concluded that [18F]FE-SA4503 showed specific binding to sigma receptors in three animal species.

Animals↗
PubMed2002

Rice uptake and distributions of radioactive 137Cs, stable 133Cs and K from soil.

The distributions of radionuclides in plant components as to radionuclide transfer to animals are important for understanding the dynamics of radionuclides in an agricultural field. Most of the non-edible parts in these components are returned to the soil as organic fertilizer where they may again be utilized in the soil-plant pathway and/or are mixed with feed for livestock. Rice plants were grown in an experimental field and separated at harvest into different components, including polished rice, rice bran, hull, leaves, stem and root, and then the distributions of radioactive 137Cs, stable 133Cs and K in these components were determined. The distribution of 137Cs in polished rice and rice bran was similar to that of 133Cs, while that of K was different. The concentration ratios of 133Cs/K in leaf blade positions increased with aging, which means that the translocation rate of 133Cs in rice plants was slower than that of K. At harvest the distribution of dry weight in polished rice to entire rice plants was 34%, and the distributions of 133Cs in the polished rice and the non-edible parts were 7 and 93%, respectively, whereas those of K in the polished rice and the non-edible parts were 2 and 98%, respectively. Findings suggest that the transfer and distribution of 133Cs, not of K, provide better information on the long-term fate of 137Cs in an agricultural environment.

Agriculture↗
PubMed2002

Potential remedy against Echinococcus multilocularis in wild red foxes using baits with anthelmintic distributed around fox breeding dens in Hokkaido, Japan.

The effect of bait-delivered anthelmintic to reduce the prevalence of Echinococcus multilocularis in wild red foxes was evaluated in Koshimizu, in the eastern part of Hokkaido, Japan. The study area (200 km2) was divided into baited and non-baited sections. The anthelmintic baits were distributed around fox den sites in the baited section every month for 13 months. After 1 year of the anthelmintic bait distribution, the prevalence of E. multilocularis in foxes, evaluated either by the parasite egg examination (from 27.1 to 5.6%) or coproantigen ELISA (from 59.6 to 29.7%), decreased in the baited section contrasting to that in the non-baited section (parasite egg: from 18.8 to 24.2%; ELISA: from 41.9 to 45.8%). The prevalence of E. multilocularis in grey red-backed vole Clethrionomys rufocanus, caught around fox dens, born after bait distribution also decreased and was significantly lower than that in non-baited section. However, within the study periods, the coproantigen-positive rate in fox faeces sporadically increased, while egg-positive rate constantly decreased. Since coproantigen ELISA can detect pre-patent infection, this observation indicates that reinfection pressure in the baited section was still high even after the 13 months of anthelmintic bait distribution. Therefore, the bait distribution longer than our study period is required for the efficient control of E. multilocularis in wild red fox population.

Animals↗
PubMed2002

DNA analysis of nosocomial infection by Enterobacter aerogenes in three cases of septicaemia in Japan.

Ceftazidime-resistant Enterobacter aerogenes was isolated from blood cultures of three patients with fever. DNA analysis using pulsed-field gel electrophoresis and ribosomal RNA gene restriction digest pattern analysis revealed that the strains were clonally similar to each other with a 79.3-96.0% homology. The same strain of E. aerogenes was isolated from a three-way stopcock connected to the indwelling catheter in one of the patients at a concentration of 45 cfu/mL. A similar strain was also isolated from the urine of one other patient on the same floor. The data suggest that E. aerogenes caused septicaemia via low bacterial contamination of a three-way stopcock in a peripheral drip intravenous infusion system in at least one patient, and that the outbreak of E. aerogenes infections was due to clonally-related strains.

Adult↗
PubMed2002

[Clinical outcome of epithelial tumors of the thymus].

OBJECTIVE AND METHODS: We retrospectively reviewed treatment and clinical outcome of thymic epithelial tumors of 64 patients over a 20-year period. Clinical staging of the tumor was done by according to Masaoka classification. Histological diagnosis of the tumors was done by according to the second edition of the WHO histologic classification system for thymic epithelial tumors. Survival rate was calculated after Kaplan-Meire method. RESULTS: Median age of patients was 53.7 years (ranged from 16 to 81). There were 30 men and 34 women. Eighteen patients had auto-immuno diseases. Sixty-two patients underwent surgery. In 57 patients resection was complete (extended thymo-thymectomy), but in the other five incomplete. The operative approach was median sternotomy in 51 patients and video-assisted thoracoscopic surgery in 6. Stage II to IV patients had postoperative mediastinal irradiation. Stage III to IV patients had postoperative cisplatin (CDDP) based chemotherapy. Inoperable patients were treated by chemo-radiotherapy. There were 42 stage I, 7 stage II, 11 stage III, 3 stage IV a, 1 stage IV b. The 5-year/10-year survival rates were 93%/89%, 71%/71%, 68.5%/--in patients with stage I, II and III. There were 5 type A tumors, 8 type AB tumors, 11 type B1 tumors, 11 type B2 tumors, 9 type B3 tumors, 11 type C tumors, the respect 5-year survival rates were 100%, 100%, 87.5%, 60%, 85.7% and 90%. Masaoka stage II to IV patients classified in B2, B3 and C type except one case. CONCLUSION: Histologic type B2, B3 and C tumors may reflect the invasive nature. Masaoka staging system and the WHO histologic classification may help the assessment and treatment of patients with thymic epithelial tumor.

Adolescent↗
PubMed2001

Effects of aging on 5-HT(1A) receptors and their functional response to 5-HT(1a) agonist in the living brain: PET study with [carbonyl-(11)C]WAY-100635 in conscious monkeys.

Age-related changes in the serotonin 5-HT(1A) receptors in the living brains of conscious young (5.9 +/- 1.8 years old) and aged (19.0 +/- 3.3 years old) monkeys (Macaca mulatta) were evaluated by [carbonyl-(11)C]WAY-100635 and high-resolution positron emission tomography (PET). The regional distribution pattern of [carbonyl-(11)C]WAY-100635 at 60-91 min postinjection was the highest in the cingulate gyrus and hippocampus, high in the frontal and temporal cortices, lower in the occipital cortex, striatum, thalamus, and raphe nuclei, and lowest in the cerebellum in both young and aged monkeys. Graphical Logan plot analysis with metabolite-corrected plasma radioactivity as an input function into the brain was applied to evaluate 5-HT(1A) receptor binding in vivo. Significant age-related decreases in 5-HT(1A) receptor binding were observed only in the frontal and temporal cortices. In the hippocampus, although 5-HT(1A) receptor binding indicated no significant age-related changes, it showed an inverse correlation with individual cortisol levels in plasma. When the 5-HT(1A) receptor agonist 8-OH-DPAT was administered intravenously at a dose of 0.1, 0.3, or 1 mg/kg 30 min after tracer injection, binding of [carbonyl-(11)C]WAY-100635 was displaced in both age groups in a dose-dependent manner. However, the degree of displacement was more marked in young than in aged monkeys. These observations demonstrated the usefulness of [carbonyl-(11)C]WAY-100635 as an indicator of the age-related changes in cortical 5-HT(1A) receptors measured noninvasively by PET. In addition, these observations suggested that the age-related impairment of 5-HT(1A) receptor responses to 8-OH-DPAT might be related to the reduced efficacy of antidepressant therapy in elderly patients with depression.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed2001

Ketamine alters the availability of striatal dopamine transporter as measured by [(11)C]beta-CFT and [(11)C]beta-CIT-FE in the monkey brain.

The effects of ketamine anesthesia on the binding of [(11)C]-labeled cocaine analogs, [(11)C]beta-CFT (2beta-carbomethoxy-3beta-(4-fluorophenyl)tropane) and [(11)C]beta-CIT-FE (N-(2-fluoroethyl)-2beta-carbomethoxy-3beta-(4-iodophenyl)tropane), to the striatal dopamine transporter (DAT) were evaluated in the monkey brain using positron emission tomography (PET). We sequentially measured the kinetics of these labeled compounds in the brains of five young-adult male rhesus monkeys (Macaca mulatta) in the conscious state, followed by those under ketamine anesthesia with continuous infusion (3 and 10 mg/kg/h). After intravenous injection, [(11)C]beta-CFT and [(11)C]beta-CIT-FE were predominantly accumulated in the striatum in both conscious and ketamine-anesthetized states. In the conscious state, the striatal uptake of [(11)C]beta-CFT and [(11)C]beta-CIT-FE continuously increased with time up to 91 min after injection. Continuous infusion of ketamine-induced higher levels of uptake of [(11)C]beta-CFT and [(11)C]beta-CIT-FE into the brain in a dose-dependent manner as compared with conscious state, and kinetic analysis with metabolite-corrected arterial input function indicated that the binding potentials (BP = k(3)/k(4)) of both compounds were elevated by ketamine. Not only [(11)C]beta-CIT-FE but also [(11)C]beta-CFT reached the equilibrium state of specific binding in the striatum within 40-50 min after injection. The present results demonstrated that ketamine significantly alters the DAT availability as measured with [(11)C]beta-CFT and [(11)C]beta-CIT-FE in the brain.

Anesthetics, Dissociative↗
PubMed2001

Facilitation of dopaminergic neural transmission does not affect [(11)C]SCH23390 binding to the striatal D(1) dopamine receptors, but the facilitation enhances phosphodiesterase type-IV activity through D(1) receptors: PET studies in the conscious monkey brain.

The present study evaluated the effects of methamphetamine and scopolamine on the striatal dopamine D(1) receptor binding, measured by [(11)C]SCH23390, and D(1) receptor-coupled cAMP messenger system, determined as phosphodiesterase type-IV (PDE-IV) activity, were evaluated in the brains of conscious monkeys using positron emission tomography (PET) with microdialysis. When methamphetamine (0.1, 0.3, and 1 mg/kg) or scopolamine (0.01, 0.03, and 0.1 mg/kg) was systemically administered, [(11)C]SCH23390 binding to D(1) receptors was not affected. With administration of methamphetamine, the striatal PDE-IV activity, as measured with R-[(11)C]rolipram (active form) and S-[(11)C]rolipram (inactive form), was dose-dependently facilitated with enhanced dopamine level in the striatal ECF. Administration of scopolamine also induced facilitated PDE-IV activity without any apparent changes in the ECF dopamine. These facilitations of PDE-IV activity were abolished by preadministration of SCH23390, but not by raclopride. These results demonstrate that, as evaluated by PDE-IV activity, the inhibition of muscarinic cholinergic receptors actually facilitated dopamine neuronal signal transduction through D(1) receptors, as observed previously on D(2) receptors with no apparent increase in the striatal ECF dopamine level, but the enhanced dopamine transmission could not detected by [(11)C]SCH23390.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed2001

An evaluation of screening for lung cancer in Niigata Prefecture, Japan: a population-based case-control study.

Although an annual screening programme for lung cancer has been carried out widely in Japan since 1987, there is insufficient evidence to confirm its efficacy in terms of reducing mortality. In order to evaluate the efficacy of the lung cancer screening which has been widely carried out in Japan since 1987, a case-control study was conducted in Niigata Prefecture, Japan. In the study area, chest X-ray examinations for all participants and sputum cytology for high-risk participants were offered annually. Case subjects, who had died from lung cancer (174), and control subjects matched by sex, year of birth, residence and smoking status (801), who had been alive at the time of diagnosis of the corresponding case, were selected from the National Health Insurance holders. Screening histories of the subjects were compared between cases and matched controls for the identical calendar period before the time of diagnosis of the cases. The odds ratio of death from lung cancer for those screened within 12 months vs those not screened was 0.401 (95% CI: 0.272-0.591) with adjustment by smoking index. Our results suggest that annual lung cancer screening might reduce mortality from lung cancer by approximately 60%.

Adult↗
PubMed2001

Age-related changes in muscarinic cholinergic receptors in the living brain: a PET study using N-[11C]methyl-4-piperidyl benzilate combined with cerebral blood flow measurement in conscious monkeys.

The effects of changes in regional cerebral blood flow (rCBF) with aging on muscarinic cholinergic receptor binding were evaluated with [15O]H(2)O and N-[11C]methyl-4-piperidyl benzilate (4-MPB) in the living brains of young (5.9+/-1.8 years old) and aged (19.0+/-3.3 years old) monkeys (Macaca mulatta) in the conscious state using high-resolution positron emission tomography (PET). For quantitative analysis of receptor binding in vivo with [11C]4-MPB, metabolite-corrected arterial plasma radioactivity curves were obtained as an input function into the brain, and graphical Patlak plot analysis was applied. In addition, two-compartment model analysis using the radioactivity curve in the cerebellum as an input function (reference analysis) was also applied to determine the distribution volume (DV=K(1)/k(2)') for [11C]4-MPB. With metabolite-corrected arterial input, Patlak plot analysis of [11C]4-MPB indicated a regionally specific decrease in muscarinic cholinergic receptor binding in vivo in the frontal and temporal cortices as well as the striatum in aged compared with young animals, showing no correlation with the degree of reduced rCBF. In contrast, on the reference analysis with cerebellar input of [11C]4-MPB, all regions assayed except the pons showed a significant age-related decrease of DV, and the degree of reduction of DV was correlated with that of rCBF. These results demonstrated the usefulness of kinetic analysis of [11C]4-MPB with metabolite-corrected arterial input, not with reference region's input, as an indicator of the aging process of cortical muscarinic cholinergic receptors in vivo measured by PET with less blood flow dependency.

Acetylcholine↗
PubMed2001

Age differences in muscarinic cholinergic receptors assayed with (+)N-[(11)C]methyl-3-piperidyl benzilate in the brains of conscious monkeys.

Age-related changes in muscarinic cholinergic receptors were evaluated with the novel ligand (+)N-[(11)C]methyl-3-piperidyl benzilate ((+)3-MPB) in the living brains of young (5.9 +/- 1.8 years old) and aged (19.0 +/- 3.3 years old) monkeys (Macaca mulatta) in the conscious state using high-resolution positron emission tomography (PET). For quantitative analysis of receptor binding in vivo, metabolite-corrected arterial plasma radioactivity curves were obtained as an input function into the brain, and kinetic analyses using the three-compartment model and graphical Logan plot analysis were applied. Kinetic analyses of [(11)C](+)3-MPB indicated a regionally specific decrease in the receptor binding in vivo determined as binding potential (BP) = k(3)/k(4) in aged animals compared with young animals. Thus, the frontal and temporal cortices as well as the striatum showed age-related reduction of muscarinic cholinergic receptors in vivo, reflecting the reduced receptor density (B(max)) determined by Scatchard plot analysis in vivo. In the hippocampus, although BP of [(11)C](+)3-MPB indicated no significant age-related changes, it showed an inverse correlation with individual cortisol levels in plasma. When the graphical Logan plot analysis was applied, all regions assayed showed significant age-related decrease of [(11)C](+)3-MPB binding. These results demonstrate the usefulness of kinetic three-compartment model analysis of [(11)C](+)3-MPB with metabolite-corrected arterial plasma input as an indicator for the aging process of the cortical muscarinic cholinergic receptors in vivo as measured by PET.

Aging↗
PubMed2001

Evaluation of PET ligands (+)N-[(11)C]ethyl-3-piperidyl benzilate and (+)N-[(11)C]propyl-3-piperidyl benzilate for muscarinic cholinergic receptors: a PET study with microdialysis in comparison with (+)N-[(11)C]methyl-3-piperidyl benzilate in the conscious monkey brain.

We developed PET ligands (+)N-[(11)C]ethyl-3-piperidyl benzilate ([(11)C](+)3-EPB) and (+)N-[(11)C]propyl-3-piperidyl benzilate ([(11)C](+)3-PPB) for cerebral muscarinic cholinergic receptors. The distribution and kinetics of the novel ligands were evaluated for comparison with the previously reported ligand (+)N-[(11)C]methyl-3-piperidyl benzilate ([(11)C](+)3-MPB) in the monkey brain (Macaca mulatta) in the conscious state using high-resolution positron emission tomography (PET). At 60-91 min postinjection, regional distribution patterns of these three ligands were almost identical, and were consistent with the muscarinic receptor density in the brain as previously reported in vitro. However, the time-activity curves of [(11)C](+)3-EPB and [(11)C](+)3-PPB showed earlier peak times of radioactivity and a faster clearance rate than [(11)C](+)3-MPB in cortical regions rich in the receptors. Kinetic analysis using the three-compartment model with time-activity curves of radioactivity in metabolite-corrected arterial plasma as input functions revealed that labeling with longer [(11)C]alkyl chain length induced lower binding potential (BP = k(3)/k(4)), consistent with the rank order of affinity of these ligands obtained by an in vitro assay using rat brain slices and [(3)H]QNB. The cholinesterase inhibitor Aricept administered at doses of 50 and 250 microg/kg increased acetylcholine level in extracellular fluid of the frontal cortex and the binding of [(11)C](+)3-PPB with the lowest affinity to the receptors was displaced by the endogenous acetylcholine induced by cholinesterase inhibition, while [(11)C](+)3-MPB with the highest affinity was not significantly affected. Taken together, these observations indicate that the increase in [(11)C]alkyl chain length could alter the kinetic properties of conventional receptor ligands for PET by reducing the affinity to receptors, which might make it possible to assess the interaction between endogenous neurotransmitters and ligand-receptor binding in vivo as measured by PET.

Animals↗
PubMed2001

Effects of aging on serotonin transporter availability and its response to fluvoxamine in the living brain: PET study with [(11)C](+)McN5652 and [(11)C](-)McN5652 in conscious monkeys.

Age-related changes in the serotonin transporter (SERT) in the living brains of conscious young (5.9 +/- 1.8 years old) and aged (19.0 +/- 3.3 years old) monkeys (Macaca mulatta) were evaluated in combination with [(11)C](+)McN5652 and its inactive enantiomer [(11)C](-)McN5652 by high-resolution positron emission tomography (PET). For the quantitative analysis of SERT binding in vivo, two serial PET scans with [(11)C](+)McN5652 and [(11)C](-)McN5652 were performed in the same animals in a day and the differences in radioactivities of [(11)C](+)McN5652 vs. [(11)C](-)McN5652 measured from 41-91 min postinjection were calculated as an estimate of specific ligand binding. Higher specific binding of SERT was observed in the thalamus and striatum, regions known to contain high densities of SERT by in vitro assay, with intermediate levels in the pons, hippocampus, cingulate gyrus, and cortical regions and lower levels in the cerebellum in both young and aged monkeys. Almost all regions assayed except the cerebellum showed significant age-related decreases in the specific binding of SERT, which showed reverse correlation with cortisol level in plasma. When the SERT blocker fluvoxamine (1 mg/kg) was administered intravenously 30 min after tracer injection, specific binding of SERT was displaced in both age groups. However, the degree of displacement was more marked in young than in aged monkeys. Cortisol level in plasma was significantly higher in aged than in young animals. These observations demonstrate the usefulness of the combined use of [(11)C](+)McN5652 and [(11)C](-)McN5652 as an indicator for the age-related changes in cortical SERT measured noninvasively by PET. In addition, these observations suggest that the age-related impairment of SERT sensitivity for fluvoxamine might be related to the reduced efficacy of antidepressant therapy in elderly patients with depression.

Aging↗