Radioactivity In Region Research Articles

Evaluation of consequences of the potential accidents in the Norwegian coastal waters

Potential accidents with modern operative nuclear submarine and with transport of spent nuclear fuel along the Norwegian coastal line have been under evaluation. Hypothetical release scenarios which include immediate discharge of release fraction and constant release of fuel corrosion products, were developed. Modelling work has been done using a compartment model developed at NRPA which includes the dispersion of radioactivity in marine regions, processes of water-sediment interactions and dose assessment modules. Collective dose-rates to man, concentration of radionuclides in biota/sea-foods and doses to marine organisms were calculated. Results from the calculation of concentrations of radionuclides in marine organisms as well as doses to man and biota are discussed.

Fluorine-18 Click Radiosynthesis and Preclinical Evaluation of a New 18F-Labeled Folic Acid Derivative

The folate receptor (FR) is highly expressed on most epithelial cancer cells, while normal cells show only restricted expression of FR. As a result, the FR is an ideal target for receptor-based molecular imaging and therapy of cancer and has become a promising target in oncology. To date, several folate-based chemotherapeutics and imaging probes such as radiopharmaceuticals for single photon emission computed tomography (SPECT) have been developed. However, an (18)F-labeled folic acid derivative suitable for positron emission tomography (PET) imaging that can be routinely applied is still lacking. In this study, a new fluorinated and radiofluorinated folic acid derivative, (18/19)F-click folate, was synthesized using click chemistry. In a convenient and very efficient two-step radiosynthesis, the isolated (18)F-click folate was obtained in good radiochemical yields of 25-35% with a specific activity of 160+/-70 GBq/micromol after <or=90 min synthesis time. The new compound was pharmacologically evaluated in vitro and in vivo. The affinity of the non-radioactive (19)F-click folate to the FR was determined in displacement studies with FR expressing KB tumor cells using (3)H-folic acid. In these in vitro binding studies, a nanomolar affinity with a K(i) of 9.76+/-3.13 nM was found for (19)F-click folate. The (18)F-labeled click folate derivative was then applied for in vivo PET studies and ex vivo biodistribution experiments using nude mice bearing KB tumor xenografts. The post mortem dissection experiments showed a high specific uptake of (18)F-click folate derivative in FR-expressing tissues. Uptake in KB tumor xenografts and kidneys (FR-positive tissue) amounted to 3.13%ID/g (94% specific blockade) and 16.53%ID/g (75% specific blockade), respectively. PET imaging using (18)F-click folate permitted a visualization of KB tumors, and blockade studies confirmed the specific accumulation of the radiotracer in vivo. However, strong hepatobiliary excretion of the new tracer led to elevated accumulation of radioactivity in the abdominal region. In conclusion, the click chemistry approach is convenient to accomplish and provided high radiochemical yields of (18)F-click folate. The new tracer showed good in vitro but limited in vivo properties. Ultimately, the (18)F-click folate emphasizes the potential of (18)F-labeled folates for receptor-based tumor PET imaging.

Metabolism of no-carrier-added 2-[18F]fluoro-L-tyrosine in rats

BackgroundSeveral fluorine-18 labelled fluoroamino acids have been evaluated as tracers for the quantitative assessment of cerebral protein synthesis in vivo by positron emission tomography (PET). Among these, 2-[18F]fluoro-L-tyrosine (2-[18F]Tyr) has been studied in mice at a low specific activity. Its incorporation into proteins is fast and metabolism via other pathways is limited. The present in vivo study was carried out in normal awake rats using no-carrier-added 2-[18F]Tyr. Under normal physiological conditions, we have studied the incorporation into proteins and the metabolism of the tracer in different brain areas.MethodsNo-carrier-added 2-[18F]Tyr was administered to awake rats equipped with chronic arterial and venous catheters. The time course of the plasma activity was studied by arterial blood sampling. The biodistribution of the activity in the main organs was studied at the end of the experiment. The distribution of radioactive species in plasma and brain regions was studied by acidic precipitation of the proteins and HPLC analysis of the supernatant.ResultsThe absolute uptake of radioactivity in brain regions was homogenous. In awake rats, no-carrier-added 2-[18F]Tyr exhibits a fast and almost quantitative incorporation into the proteins fractions of cerebellum and cortex. In striatum, this incorporation into proteins and the unchanged fraction of the tracer detected by HPLC could be lower than in other brain regions.ConclusionThis study confirms the potential of 2-[18F]fluoro-L-tyrosine as a tracer for the assessment of the rate of protein synthesis by positron emission tomography. The observed metabolism suggests a need for a correction for the appearance of metabolites, at least in plasma.

Quantitative Analysis of NK1Receptor in the Human Brain Using PET with18F-FE-SPA-RQ

18F-fluoroethyl-SPA-RQ (18F-FE-SPA-RQ) was recently developed as a radioligand for the measurement of neurokinin 1 (NK1) receptor with PET. In this study, we used 18F-FE-SPA-RQ with PET to visualize and quantify NK1 receptor in the human brain. PET scans were performed on 7 healthy men after intravenous injection of 18F-FE-SPA-RQ. Binding potential (BPND) was calculated by the indirect kinetic, simplified reference tissue model (SRTM), and ratio methods. The indirect kinetic method was used as the gold standard method and was compared with the SRTM method, with scan times of 180, 270, and 330 min, and with the ratio method, with time integration intervals of 120-180, 210-270, and 300-330 min. The cerebellum was used as the reference brain region. Regional radioactivity was highest in the caudate head and putamen; mid level in the parahippocampus, cerebral cortex, and thalamus; and lowest in the cerebellum. BPND values by the indirect kinetic method were 3.15 +/- 0.36, 3.11 +/- 0.66, 1.17 +/- 0.25, and 0.46 +/- 0.14 in the caudate, putamen, parahippocampal region, and thalamus, respectively. For cerebral cortical regions, BPND values by the indirect kinetic method were 0.94 +/- 0.23, 0.82 +/- 0.15, 0.76 +/- 0.15, and 0.69 +/- 0.16 in the occipital, temporal, frontal, and anterior cingulate cortices, respectively. BPND values by the SRTM and ratio methods were in good agreement with those by the indirect kinetic method (r = 0.94-0.98). The regional distribution of 18F-FE-SPA-RQ was in agreement with previous PET studies and postmortem studies of NK1 receptor in the human brain. The ratio method will be useful for clinical research of psychiatric disorders, for the estimation of NK1 receptor without arterial blood sampling and long dynamic PET.

11C]CHIBA-1001 as a Novel PET Ligand for α7 Nicotinic Receptors in the Brain: A PET Study in Conscious Monkeys

BackgroundThe α7 nicotinic acetylcholine receptors (nAChRs) play an important role in the pathophysiology of neuropsychiatric diseases such as schizophrenia and Alzheimer's disease. However, there are currently no suitable positron emission tomography (PET) radioligands for imaging α7 nAChRs in the intact human brain. Here we report the novel PET radioligand [11C]CHIBA-1001 for in vivo imaging of α7 nAChRs in the non-human primate brain.Methodology/Principal FindingsA receptor binding assay showed that CHIBA-1001 was a highly selective ligand at α7 nAChRs. Using conscious monkeys, we found that the distribution of radioactivity in the monkey brain after intravenous administration of [11C]CHIBA-1001 was consistent with the regional distribution of α7 nAChRs in the monkey brain. The distribution of radioactivity in the brain regions after intravenous administration of [11C]CHIBA-1001 was blocked by pretreatment with the selective α7 nAChR agonist SSR180711 (5.0 mg/kg). However, the distribution of [11C]CHIBA-1001 was not altered by pretreatment with the selective α4β2 nAChR agonist A85380 (1.0 mg/kg). Interestingly, the binding of [11C]CHIBA-1001 in the frontal cortex of the monkey brain was significantly decreased by subchronic administration of the N-methyl-D-aspartate (NMDA) receptor antagonist phencyclidine (0.3 mg/kg, twice a day for 13 days); which is a non-human primate model of schizophrenia.Conclusions/SignificanceThe present findings suggest that [11C]CHIBA-1001 could be a novel useful PET ligand for in vivo study of the receptor occupancy and pathophysiology of α7 nAChRs in the intact brain of patients with neuropsychiatric diseases such as schizophrenia and Alzheimer's disease.

Targeting of Lectinlike Oxidized Low-Density Lipoprotein Receptor 1 (LOX-1) with99mTc-Labeled Anti–LOX-1 Antibody: Potential Agent for Imaging of Vulnerable Plaque

Lectinlike oxidized low-density lipoprotein (LDL) receptor 1 (LOX-1), a cell surface receptor for oxidized LDL, has been implicated in vascular cell dysfunction related to plaque instability, which could be a potential target for an atherosclerosis imaging tracer. In this study, we designed and prepared (99m)Tc-labeled anti-LOX-1 monoclonal IgG and investigated its usefulness as an atherosclerosis imaging agent. Anti-LOX-1 monoclonal IgG and control mouse IgG2a were labeled with (99m)Tc after derivatization with 6-hydrazinonicotinic acid to yield (99m)Tc-LOX-1-mAb and (99m)Tc-IgG2a, respectively. Myocardial infarction-prone Watanabe heritable hyperlipidemic (WHHLMI) rabbits (atherosclerosis model) and control rabbits were injected intravenously with these probes, and in vivo planar imaging was performed. At 24 h after the injection, the aortas were removed, and radioactivity was measured. Autoradiography and histologic studies were performed with serial aortic sections. The level of (99m)Tc-LOX-1-mAb accumulation was 2.0-fold higher than the level of (99m)Tc-IgG2a accumulation in WHHLMI rabbit aortas, and the level of (99m)Tc-LOX-1-mAb accumulation in WHHLMI rabbit aortas was 10.0-fold higher than the level of (99m)Tc-LOX-1-mAb accumulation in control rabbit aortas. In vivo imaging clearly visualized the atherosclerotic aortas of WHHLMI rabbits. Autoradiography and histologic studies revealed that regional (99m)Tc-IgG2a accumulation was independent of the histologic grade of the lesions; however, regional (99m)Tc-LOX-1-mAb accumulation was significantly correlated with LOX-1 expression density and the vulnerability index. The highest level of (99m)Tc-LOX-1-mAb accumulation, expressed as {radioactivity in region of interest (Bq/mm(2))/[injected radioactivity (Bq)/animal body weight (g)]} x 10(2), was found in atheromatous lesions (3.8 +/- 1.1 [mean +/- SD]), followed in decreasing order by fibroatheromatous lesions (2.0 +/- 1.0), collagen-rich lesions (1.6 +/- 0.8), and neointimal lesions (1.4 +/- 0.7). The level of (99m)Tc-LOX-1-mAb accumulation in grade IV atheroma was higher than that in neointimal lesions or other, more stable lesions. Nuclear imaging of LOX-1 expression with (99m)Tc-LOX-1-mAb may be a useful means for predicting atheroma at high risk for rupture.

2-(2′-((Dimethylamino)methyl)-4′-(3-[18F]fluoropropoxy)-phenylthio)benzenamine for positron emission tomography imaging of serotonin transporters

A new (18)F ligand, 2-(2'-((dimethylamino)methyl)-4'-(3-[(18)F]fluoropropoxy)-phenylthio)benzenamine ([(18)F]1), for positron emission tomography (PET) imaging of serotonin transporters (SERT) was evaluated. Binding affinity was determined through in vitro binding assays with LLC-PK1 cells overexpressing SERT, NET or DAT (LLC-SERT, LLC-NET and LLC-DAT) and with rat cortical homogenates. Localization and selectivity of [(18)F]1 binding in vivo were evaluated by biodistribution, autoradiography and A-PET imaging studies in rats. This compound displayed excellent binding affinity for SERT in vitro with K(i)=0.33 and 0.24 nM in LLC-SERT and rat cortical homogenates, respectively. Biodistribution studies with [(18)F]1 showed good brain uptake (1.61% dose/g at 2 min postinjection), high uptake into the hypothalamus (1.22% dose/g at 30 min) and a high target-to-nontarget (hypothalamus to cerebellum) ratio of 9.66 at 180 min postinjection. Pretreatment with a SERT selective inhibitor considerably inhibited [(18)F]1 binding in biodistribution studies. Ex vivo autoradiography reveals [(18)F]1 localization to brain regions with high SERT density, and this binding was blocked by pretreatment with SERT selective inhibitors. Small animal PET (A-PET) imaging in rats provided clear images of tracer localization in the thalamus, midbrain and striatum. In A-PET chasing experiments, injecting a SERT selective inhibitor 75 min post-tracer injection causes a dramatic reduction in regional radioactivity and the target-to-nontarget ratio. The results of the biological studies and the ease of radiosynthesis with moderately good radiochemical yield (RCY=10-35%) make [(18)F]1 an excellent candidate for SERT PET imaging.

Synthesis and In Vivo Evaluation of Halogenated N,N-Dimethyl-2-(2′-amino-4′-hydroxymethylphenylthio)benzylamine Derivatives as PET Serotonin Transporter Ligands

N, N-dimethyl-2-(2'-amino-4'-hydroxymethylphenylthio)benzylamine (38), substituted on ring A, was reported to display high binding affinity and selectivity to the human brain serotonin transporter (SERT). In an attempt to explore the potential of compounds substituted on ring B of the phenylthiophenyl core structure, three derivatives of 38 were synthesized: N, N-dimethyl-2-(2'-amino-4'-hydroxymethyl-phenylthio)-5-fluorobenzylamine (35), N, N-dimethyl-2-(2'-amino-4'-hydroxymethyl-phenylthio)-5-bromobenzylamine (36), and N, N-dimethyl-2-(2'-amino-4'-hydroxymethyl-phenylthio)-5-iodobenzylamine (37). The in vitro binding studies in cells transfected with human SERT, norepinephrine transporter (NET), and dopamine transporter (DAT) showed that 35, 36, and 37 exhibited high SERT affinity with K is (SERT) = 1.26, 0.29, and 0.31 nM (vs [(3)H]citalopram), respectively. [(11)C]-(35), [(11)C]-(36), and [(11)C]-( 37) were prepared by methylation of their monomethyl precursors 16, 17, and 18, with [(11)C]iodomethane in 28, 11, and 14% radiochemical yields, respectively. The microPET images of [(11)C]-(35), [(11)C]-(36), and [(11)C]-(37) showed high uptake in the monkey brain regions rich in SERT with peak midbrain to cerebellum ratios of 3.41, 3.24, and 3.00 at 85 min post-injection, respectively. In vivo bindings of [(11)C]-(35), [(11)C]-(36), and [(11)C]-(37) were shown to be specific to the SERT as displacement with citalopram (a potent SERT ligand) reduced radioactivity in SERT-rich regions to the cerebellum level. These results suggest that [(11)C]-(35), [(11)C]-(36), and [(11)C]-(37) could be potential agents for mapping human SERT by PET and radiolabeling 37 with iodine-123, which could afford the first SPECT SERT imaging agent exhibiting fast kinetics.

Reduced frontal perfusion in depressed postmenopausal women: A SPECT study with WCST

Objectives To investigate frontal cerebral blood flow (CBF) in depressed postmenopausal women and its relation to cognitive function and the severity of depressive symptoms. Methods Regional CBF of 20 unmedicated depressed postmenopausal women was measured using Tc-99m HMPAO SPECT, both at rest and during frontal activation using the Wisconsin card sorting test (WCST). Frontal CBF was semi-quantified by comparing the radioactivity in the prefrontal region to the cerebellum (F/C ratio). We measured the severity of the symptoms of depression using the hospital anxiety and depression scale (HADS) and cognitive function using the mini-mental status examination (MMSE). Results At rest, there was no difference in frontal CBF between patients with moderate or severe (HADS ≥ 11) and patients with mild depressive symptoms (HADS < 11). During the WCST, however, the HADS ≥ 11 group did not score as well as the HADS < 11 group ( P = 0.03). The changes in F/C ratios were inversely correlated with HADS scores ( r = −0.43, P = 0.05) and positively correlated with MMSE scores ( r = 0.58, P = 0.004). After adjusting for age, F/C ratios were significantly correlated with MMSE ( P = 0.002), but not with HADS scores. Conclusions Frontal CBF did not increase in postmenopausal women with moderate/severe symptoms of depression during the WCST activation task, and reduced frontal CBF was related to the impairment of cognitive function. The combination of the functional activation test and SPECT imaging powerfully revealed this functional disease, which remains undetectable using more common baseline measurements.

Coexistence of Adrenal Cushing Syndrome and Pheochromocytoma in a “Corticomedullary Adenoma”

Mixed pheochromocytoma and adrenal cortical adenoma (corticomedullary adenoma) is extremely rare. We report a 41-year-old woman diagnosed preoperatively with Cushing syndrome of adrenal origin. Nonsuppressible serum cortisol and 24-hour urine free cortisol levels by a standard low-dose dexamethasone suppression test with a low plasma adrenocorticotropic hormone (ACTH) level suggested ACTH-independent Cushing syndrome. Magnetic resonance imaging (MRI) revealed a left adrenal mass about 4 cm in diameter, showing a slightly heterogenous signal drop in chemical shift imaging, suggesting high lipid content in the tumor. The T2-weighted image, however, had a mildly high signal, rather than the typical normal to low signal characteristic of a cortical adenoma. 131I-6β-iodomethyl-norcholesterol (NP-59) scintigraphy revealed early accumulation of radioactivity in the left suprarenal region, suggesting a functioning cortical tumor. The patient underwent left adrenalectomy, but the surgery caused a marked elevation of systolic blood pressure (greater than 200 mm Hg). The suspicion of pheochromocytoma was entertained. Mixed pheochromocytoma and adrenal cortical adenoma (corticomedullary adenoma) were disclosed by immunohistochemical stains and electron microscopic examination. This case is the fifth reported pathologically proven corticomedullary adenoma. We include special image findings that contain characteristics of both cortical and medullary components.

Longitudinal, Quantitative Assessment of Amyloid, Neuroinflammation, and Anti-Amyloid Treatment in a Living Mouse Model of Alzheimer's Disease Enabled by Positron Emission Tomography

We provide the first evidence for the capability of a high-resolution positron emission tomographic (PET) imaging system in quantitatively mapping amyloid accumulation in living amyloid precursor protein transgenic (Tg) mice. After the intravenous administration of N-[11C]methyl-2-(4'-methylaminophenyl)-6-hydroxybenzothiazole (or [11C]PIB for "Pittsburgh Compound-B") with high-specific radioactivity, the Tg mice exhibited high-level retention of radioactivity in amyloid-rich regions. PET investigation for Tg mice over an extended range of ages, including longitudinal assessments, demonstrated age-dependent increase in radioligand binding consistent with progressive amyloid accumulation. Reduction in amyloid levels in the hippocampus of Tg mice was also successfully monitored by multiple PET scans along the time course of anti-amyloid treatment using an antibody against amyloid beta peptide (Abeta). Moreover, PET scans with [18F]fluoroethyl-DAA1106, a radiotracer for activated glia, were conducted for these individuals parallel to amyloid imaging, revealing treatment-induced neuroinflammatory responses, the magnitude of which intimately correlated with the levels of pre-existing amyloid estimated by [11C]PIB. It is also noteworthy that the localization and abundance of [11C]PIB autoradiographic signals were closely associated with those of N-terminally truncated and modified Abeta, AbetaN3-pyroglutamate, in Alzheimer's disease (AD) and Tg mouse brains, implying that the detectability of amyloid by [11C]PIB positron emission tomography is dependent on the accumulation of specific Abeta subtypes. Our results support the usefulness of the small animal-dedicated PET system in conjunction with high-specific radioactivity probes and appropriate Tg models not only for clarifying the mechanistic properties of amyloidogenesis in mouse models but also for preclinical tests of emerging diagnostic and therapeutic approaches to AD.

Comparison of 99mTc-annexin A5 with 18F-FDG for the detection of atherosclerosis in ApoE−/− mice

(99m)Tc-annexin A5, a marker of ongoing apoptosis, and (18)F-FDG, a marker of the increased metabolism of inflammatory cells, are supposed to be useful in the detection of metabolically active atheroma. This study reports a comparison of the intralesional distribution of these tracers in relation to lesion development in ApoE-/- mice. Male ApoE-/- mice (n = 12-14/group) were maintained on a Western-type diet after the age of 5 weeks. At 25 weeks, (99m)Tc-annexin A5 or (18)F-FDG was injected and the aortas were harvested for autoradiography (ARG) and Oil Red O staining. Regional radioactivity accumulation was compared in relation to the Oil Red O staining score (ranging from 0 to 3, a semiquantitative parameter for evaluating lesion development). Both (99m)Tc-annexin A5 and (18)F-FDG showed preferential uptake into atherosclerotic lesions, with higher uptake levels for (18)F-FDG (mean, 56.07 %IDxkg/m(2)) than for (99m)Tc-annexin A5 (mean, 10.38 %IDxkg/m(2)). The regional uptake levels of each tracer correlated with the Oil Red O staining score (r = 0.65, p < 0.05 for (99m)Tc-annexin A5; r = 0.56, p < 0.05 for (18)F-FDG). The uptake ratios of advanced lesions (score >0.5) to early lesions (score <0.5) were significantly higher for (99m)Tc-annexin A5 than for (18)F-FDG (f = 4.73, p = 0.03). Both (99m)Tc-annexin A5 and (18)F-FDG accumulate in atherosclerotic lesions and correlate with the severity of each lesion. The higher absolute uptake levels of (18)F-FDG may be advantageous for lesion detection, whereas the preferential uptake of (99m)Tc-annexin A5 in advanced lesions may be a useful indicator of late-stage lesions or vulnerable plaque transformation.

Comparative assessment of statistical brain MR image segmentation algorithms and their impact on partial volume correction in PET

Magnetic resonance imaging (MRI)-guided partial volume effect correction (PVC) in brain positron emission tomography (PET) is now a well-established approach to compensate the large bias in the estimate of regional radioactivity concentration, especially for small structures. The accuracy of the algorithms developed so far is, however, largely dependent on the performance of segmentation methods partitioning MRI brain data into its main classes, namely gray matter (GM), white matter (WM), and cerebrospinal fluid (CSF). A comparative evaluation of three brain MRI segmentation algorithms using simulated and clinical brain MR data was performed, and subsequently their impact on PVC in 18F-FDG and 18F-DOPA brain PET imaging was assessed. Two algorithms, the first is bundled in the Statistical Parametric Mapping (SPM2) package while the other is the Expectation Maximization Segmentation (EMS) algorithm, incorporate a priori probability images derived from MR images of a large number of subjects. The third, here referred to as the HBSA algorithm, is a histogram-based segmentation algorithm incorporating an Expectation Maximization approach to model a four-Gaussian mixture for both global and local histograms. Simulated under different combinations of noise and intensity non-uniformity, MR brain phantoms with known true volumes for the different brain classes were generated. The algorithms' performance was checked by calculating the kappa index assessing similarities with the “ground truth” as well as multiclass type I and type II errors including misclassification rates. The impact of image segmentation algorithms on PVC was then quantified using clinical data. The segmented tissues of patients' brain MRI were given as input to the region of interest (RoI)-based geometric transfer matrix (GTM) PVC algorithm, and quantitative comparisons were made. The results of digital MRI phantom studies suggest that the use of HBSA produces the best performance for WM classification. For GM classification, it is suggested to use the EMS. Segmentation performed on clinical MRI data show quite substantial differences, especially when lesions are present. For the particular case of PVC, SPM2 and EMS algorithms show very similar results and may be used interchangeably. The use of HBSA is not recommended for PVC. The partial volume corrected activities in some regions of the brain show quite large relative differences when performing paired analysis on 2 algorithms, implying a careful choice of the segmentation algorithm for GTM-based PVC.

123I]TPCNE—A novel SPET tracer for the sigma‐1 receptor: First human studies and in vivo haloperidol challenge

[123I]TPCNE (1(trans-[123I]iodopropen-2-yl)-4-[(4-cyanophenoxy)methyl] piperidine; Ki = 0.67 nM; log P = 3.36) is a novel sigma-1 receptor SPET ligand. In this study, we developed an optimized labeling method for [123I]TPCNE and investigated the kinetics, binding characteristics, and whole-body distribution of this tracer for the first time in humans. We also performed a challenge with the sigma-1 receptor antagonist haloperidol against [123I]TPCNE. Seven healthy volunteers were recruited. Dynamic brain SPET scans were performed following i.v. administration of 185 MBq [123I]TPCNE in all seven subjects. Three of the subjects were given oral haloperidol (2.5 mg) approximately 1 h before the scan. The dynamic data were analyzed with both reversible and irreversible compartmental models.[123I]TPCNE showed high uptake in brain and liver. All non-haloperidol-treated subjects showed a high whole-brain uptake (average: 8.7% of injected activity). No significant clearance of the tracer was seen up to 30 h post injection. In the haloperidol-treated subjects, the time-activity curves clearly demonstrated clearance of the tracer from the brain. Regional radioactivity concentrations were reduced by haloperidol from 42% in the cerebellum to 73% in the thalamus.[(123)I]TPCNE demonstrated high brain uptake, with highest binding found in the posterior cingulate. A region in which binding was unaffected by haloperidol pretreatment could not be identified, and the time-activity data were best described by an irreversible model.

Unexpected Finding of Umbilical Hernia During Peritoneal Scintigraphy

A 48-year-old woman had liver cirrhosis complicated with intractable ascites. She underwent a Denver shunt (peritoneovenous shunt) procedure 1 year ago. Suspicion of dysfunction of the Denver shunt led to her referral for peritoneal scintigraphy. Instead of confirmation of shunt dysfunction, there were also findings of bilateral peritoneopleural communications. Nevertheless, it was also found as well-demarcated, circumferential accumulation of the radiotracer as well as scattered distributed, photopenic areas within the center of the abdomen, which was distinguished from the peripheral diffuse distribution of radioactivity in the peripheral abdominal region. The assumption of the accumulation of radiotracer in the center of the abdomen after physical examination was an umbilical hernia that was further confirmed by subsequent abdominal computed tomography.

Effects of image reconstruction algorithm on neurotransmission PET studies in humans: Comparison between filtered backprojection and ordered subsets expectation maximization

Both reconstruction algorithms, filtered backprojection (FBP) and ordered subsets expectation maximization (OSEM), are widely used in clinical positron emission tomography (PET) studies. Image reconstruction for most neurotransmission PET scan data is performed by FBP, while image reconstruction for whole-body [18F]FDG scan data is usually performed by OSEM. Although several investigators have compared FBP and OSEM in terms of the quantification of regional radioactivity and physiological parameters calculated from PET data, only a few studies have compared the two reconstruction algorithms in PET studies that estimate neurotransmission, i.e., neuroreceptor and neurotransporter binding. In this study we compared mean regional radioactivity concentration in the late phase and binding potential (BP) between FBP and OSEM algorithms in neurotransmission PET studies for [11C]raclopride and [11C]DASB. Dynamic PET scans with [11C]raclopride in 3-dimensional mode were performed on seven healthy subjects. Dynamic PET scans with [11C]DASB in 2-dimensional mode were performed on another seven subjects. OSEM images were post-filtered so that its transverse spatial resolution became similar to that of FBP with the same Hanning filter (Kernel FWHM 6 mm). In both PET studies we calculated the BP of [11C]raclopride and [11C]DASB by a reference tissue model for each ROI (region of interest). There was no significant difference in mean regional radioactivity concentration between FBP and OSEM for [11C]raclopride and [11C]DASB. Only +2.4 - +3.2%, but still a significant difference in BP of [11C]raclopride between FBP and OSEM was observed in the striatum. There was no significant difference in BP between FBP and OSEM in other than the striatum for [11C]raclopride and in all regions for [11C]DASB. In addition, there was no significant difference in root mean square error between FBP and OSEM when BP was calculated. The BP values were similar between FBP and OSEM algorithms with [11C]raclopride and [11C]DASB. This study indicates that OSEM can be used for human neurotransmission PET studies for calculating BP although OSEM was not necessarily superior to FBP in the present study.

Dopamine Storage Capacity in Caudate and Putamen of Patients with Early Parkinson's Disease: Correlation with Asymmetry of Motor Symptoms

Conventional graphical analysis of positron emission tomography (PET) recordings of the cerebral uptake of the DOPA decarboxylase substrate [(18)F]fluorodopa (FDOPA) assumes irreversible trapping of [(18)F]fluorodopamine formed in the brain. However, 4-h long PET recordings allow the estimation of a rate constant for elimination of [(18)F]fluorodopamine from the brain (k(loss)), from which can be calculated an effective distribution volume (EDV(1)), which is an index of [(18)F]fluorodopamine storage capacity. We earlier developed a method employing 2-h long FDOPA recordings for the estimation of k(loss) and EDV, here defined as EDV(2). This method is based on subtraction of the calculated brain concentrations of the FDOPA metabolite O-methyl-FDOPA, rather than the subtraction of the entire radioactivity in a reference region. We now extend this method for the parametric mapping of these parameters in the brain of healthy aged volunteers and patients with Parkinson's disease (PD), with asymmetry of motor symptoms. For parametric mapping, we use a novel application of a multilinear solution for the two-tissue compartment FDOPA model. We also test a new application of the Logan graphical analysis for mapping of the FDOPA distribution volume at equilibrium. The estimates of k(loss) and EDV(2) were more sensitive for the discrimination of biochemical abnormality in the putamen of patients with early PD relative to healthy aged subjects, than was the conventional net influx estimate. Of the several methods, multilinear estimates of EDV(2) were most sensitive for discrimination of PD and normal putamen. However, k(loss) was most sensitive for detecting biochemical asymmetry in the putamen of PD patients, and only k(loss) also detected in the caudate of PD patients a decline in the retention of [(18)F]fluorodopamine relative to healthy aged control subjects.

Radiation effects in wild terrestrial vertebrates – the EPIC collection

The paper presents data on radiation effects in populations of wild vertebrate animals inhabiting contaminated terrestrial ecosystems. The data were extracted from the database “Radiation effects on biota”, compiled within the framework of the EC Project EPIC (2000–2003). The data collection, based on publications in Russian, demonstrates radiation effects in the areas characterized with high levels of radionuclides (Kyshtym radioactive trace; “spots” of enhanced natural radioactivity in the Komi region of Russia; territories contaminated from the Chernobyl fallout). The data covers a wide range of exposures from acute accidental irradiation to lifetime exposures at relatively low dose rates. Radiation effects include mortality, changes in reproduction, decrease of health, ecological effects, cytogenetic effects, adaptation to radiation, and others. Peculiarities of radiation effects caused by different radionuclides are described, also the severity of effects as they appear in different organisms (e.g. mice, frogs, birds, etc.).

Gamma-emitting radionuclides in the shallow marine sediments off the Sindh coast, Arabian Sea

Determination of gamma emitting radionuclides in shallow marine sediments off the Sindh coast has been carried out using a gamma spectrometry technique. The activity concentration measured in various sediment samples off the Sindh coast has been found to vary from 15.93 +/- 5.22 to 30.53 +/- 4.70 Bq kg(-1) for 226Ra, from 11.72 +/- 1.22 to 33.94 +/- 1.86 Bq kg(-1) for 228Ra and from 295.22 +/- 32.83 to 748.47 +/- 28.75 Bq kg(-1) for 40K. The calculated mean values of radium equivalent activity, absorbed dose rate and effective dose are 98 Bq kg(-1), 49 nGy h(-1) and 0.06 mSv y(-1), respectively. No artificial radionuclide was detected in the samples measured from the study area. As no data on radioactivity of the coastal environment of Pakistan are available, the data presented here will serve as baseline information on radionuclide concentration in shallow sea sediments off the Sindh coast. The data will also be useful for tracking pollution inventories from unusual radiological events (if any) in the territorial waters of the study area. Further, the information presented will contribute to modelling of a regional radioactivity database from the perspectives of the International Atomic Energy Agency's Asia-Pacific Marine Radioactivity Database and Global Marine Radioactivity Database.

Cerebral Metabolic Dysfunction and Impaired Vigilance in Recently Abstinent Methamphetamine Abusers

Methamphetamine (MA) abusers have cognitive deficits, abnormal metabolic activity and structural deficits in limbic and paralimbic cortices, and reduced hippocampal volume. The links between cognitive impairment and these cerebral abnormalities are not established. We assessed cerebral glucose metabolism with [F-18]fluorodeoxyglucose positron emission tomography in 17 abstinent (4 to 7 days) methamphetamine users and 16 control subjects performing an auditory vigilance task and obtained structural magnetic resonance brain scans. Regional brain radioactivity served as a marker for relative glucose metabolism. Error rates on the task were related to regional radioactivity and hippocampal morphology. Methamphetamine users had higher error rates than control subjects on the vigilance task. The groups showed different relationships between error rates and relative activity in the anterior and middle cingulate gyrus and the insula. Whereas the MA user group showed negative correlations involving these regions, the control group showed positive correlations involving the cingulate cortex. Across groups, hippocampal metabolic and structural measures were negatively correlated with error rates. Dysfunction in the cingulate and insular cortices of recently abstinent MA abusers contribute to impaired vigilance and other cognitive functions requiring sustained attention. Hippocampal integrity predicts task performance in methamphetamine users as well as control subjects.