Objectives: Focal lesions in infants with congenital hyperinsulinism (HI) represent areas of adenomatosis that express a paternally derived ATP-sensitive potassium channel mutation due to embryonic loss of heterozygosity for the maternal 11p region. This study evaluated the accuracy of 18 F-fluoro-L-dihydroxyphenylalanine ([ 18 F]DOPA) positron emission tomography (PET) scans in diagnosing focal vs. diffuse disease and identifying the location of focal lesions.Design: A total of 50 infants with HI unresponsive to medical therapy were studied. Patients were injected iv with [18 F]DOPA, and PET scans were obtained for 50 -60 min. Images were coregistered with abdominal computed tomography scans. PET scan interpretations were compared with histological diagnoses. Results

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Central nervous system (CNS) demyelination represents the pathological hallmark of multiple sclerosis (MS) and contributes to other neurological conditions. Quantitative and specific imaging of demyelination would thus provide critical clinical insight. Here, we investigated the possibility of targeting axonal potassium channels to image demyelination by positron emission tomography (PET). These channels, which normally reside beneath the myelin sheath, become exposed upon demyelination and are the target of the MS drug, 4-aminopyridine (4-AP). We demonstrate using autoradiography that 4-AP has higher binding in non-myelinated and demyelinated versus well-myelinated CNS regions, and describe a fluorine-containing derivative, 3-F-4-AP, that has similar pharmacological properties and can be labeled with 18F for PET imaging. Additionally, we demonstrate that [18F]3-F-4-AP can be used to detect demyelination in rodents by PET. Further evaluation in Rhesus macaques shows higher binding in non-myelinated versus myelinated areas and excellent properties for brain imaging. Together, these data indicate that [18F]3-F-4-AP may be a valuable PET tracer for detecting CNS demyelination noninvasively.

The characteristics of the fission step following a binary deep-inelastic interaction have been reconstructed for three-body events detected in the reactions 100 Mo + 100 Mo at 18.7A MeV and 120 Sn -f-120 Sn at 18.AA MeV. The observed anisotropy of the in-plane angular distributions points to the fast decay of a rotating (and strongly deformed) nuclear object formed at the end of the deep-inelastic interaction. The derived time scale of the process indicates that asymmetric divisions are faster than symmetric ones. PACS numbers: 25.70.Lm, 25.70.Gh Interest in nuclear fission in general and particularly in the determination of its characteristic time scale has been revived after a series of recent measurements of prescission neutrons (see Ref.[1], and references therein).As compared to particle emission, nuclear fission is expected to be a slower process, due to the complex change of collective degrees of freedom involved in it [2]. Experimentally, this expectation was repeatedly confirmed by the observation of isotropic in-plane angular distributions in a large number of fusion-fission reactions, as well as in the sequential fission decay of heavy reaction products [3]. This fact points to the nucleus undergoing, on the average, at least one full rotation before scission and sets a lower limit of several 10~2 1 s for the fission time scale. Recent studies on neutron emission in fusion-fission reactions have argued that the motion towards scission is highly viscous and leads to fission times of the order of 10 -20 s to 10 -19 s [1,4-6]. This time seems to decrease with increasing mass asymmetry, as reported in recent works based on the detection of neutrons [1,7,8] or light charged particles [9] in coincidence with heavy fragments.Some indications of short time scales (« 10~2 1 s) were obtained also from fragment correlations in sequential fissionlike decays following collisions at intermediate bombarding energies [10,11] and from "proximity" modulations of the relative velocity of sequential-fission fragments in the 129 Xe+ 122 Sn collision at 12.5,4 MeV [12]. In this latter case, anisotropic in-plane angular distributions were also observed, pointing to three-body events characterized by a preferential collinearity of the three fragments, with the lighter fission fragment roughly located in between the other two.This Letter presents for the first time evidence that the in-plane angular distribution of a fissionlike decay evolves from a "well behaved" isotropic shape for symmetric splits towards a strong anisotropy for the most asymmetric splits. Moreover, a novel and independent method of estimating the time scale of the process is suggested, based on the analysis of the shape of the in-plane angular distribution.Two symmetric systems were investigated, namely, 100 Mo + 100 Mo at 18.7A MeV and 120 Sn + 120 Sn at 18.4A MeV. Heavy fragments (A > 20) were detected with twelve position-sensitive gas detectors covering about 75% of the forward hemisphere [13,14]. Prom the measured velocity vectors, primary (pre-e...

We have used computer simulations to compare two designs for a PET scanner dedicated to breast imaging with a whole-body PET scanner. The new designs combine high spatial resolution, high sensitivity, and good energy resolution to detect small, low-contrast masses. The detectors are position sensitive NaI(Tl) scintillators. The first design is a ring scanner surrounding the breast and the second consists of two planar detectors placed on opposite sides of the breast. We have employed standard performance measures to compare the different designs: contrast, percentage standard deviation of the background, and signal-to-noise ratios of reconstructed images. The results of the simulations show that both of the proposed designs have better lesion detectability than a whole-body scanner. The results also show that contrast is higher in the ring breast system but that the noise is lower in the planar breast system. Overall, the ring system yields images with the best signal-to-noise ratios, although the planar system offers practical advantages for imaging the breast and axilla.

In recent years it has been shown that PET is capable of obtaining in vivo metabolic images of small animals. These serve as models to study the development and progress of diseases within humans. Imaging small animals requires not only image resolution better than 2 mm, but also high sensitivity in order to image ligands with low specific activity or radiochemical yields. Toward achieving these goals, we have developed a discrete 2 2 10 mm 3 GSO Anger-logic detector for use in a high resolution, high sensitivity, and high count-rate animal PET scanner. This detector uses relatively large 19 mm diameter photomultiplier tubes (PMT), but nevertheless achieves good spatial and energy resolution. The scanner (A-PET) has a port diameter of 21 cm, transverse field-of-view of 12.8 cm, axial length of 11.6 cm, and operates in 3-D volume imaging mode. The absolute coincidence sensitivity is 1.3% for a point source. Due to the use of large PMTs in an Anger design, the encoding ratio (number of crystals/PMT) is high, which reduces the complexity and leads to a cost-effective scanner. Simulation results show that this scanner can achieve high NEC rates for small cylindrical phantoms due to its high sensitivity and low deadtime. Initial measurements show that our design goals for spatial resolution and sensitivity were realized in the prototype scanner.

Abstract. Events with 2, 3 and 4 heavy fragments (A > 20) detected in the reactions ~~176 + l~176 at 18.7, 23.7 A" MeV and ~2~ + ~Z~ at 18.4 A' MeV were analyzed by means of an improved version of the kinematic coincidence method. The phase-space distributions prove that 3-(and possibly 4-) body events predominantly originate from a two-step mechanism and are compatible with the hypothesis of a binary deep-inelastic interaction followed by the further fissionlike decay of one (or both) of the primary fragments. The characteristics of the fission step -mass asymmetry, relative velocity, in-plane and out-of-plane angles -have been reconstructed for the 3-body events and indications are found that nonequilibrium effects at the end of the deep-inelastic phase may influence the fissionlike decay.

Purpose The primary purpose of this study was to assess the biodistribution and radiation dose resulting from administration of 18F-EF5, a lipophilic 2-nitroimidazole hypoxia marker in ten cancer patients. For three of these patients (with glioblastoma) unlabeled EF5 was additionally administered to allow the comparative assessment of 18F-EF5 tumor uptake with EF5 binding, the latter measured in tumor biopsies by fluorescent anti-EF5 monoclonal antibodies. Methods 18F-EF5 was synthesized by electrophilic addition of 18F2 gas, made by deuteron bombardment of a neon/fluorine mixture in a high-pressure gas target, to an allyl precursor in trifluoroacetic acid at 0° then purified and administered by intravenous bolus. Three whole-body images were collected for each of ten patients using an Allegro (Philips) scanner. Gamma counts were determined in blood, drawn during each image, and urine, pooled as a single sample. PET images were analyzed to determine radiotracer uptake in several tissues and the resulting radiation dose calculated using OLINDA software and standard phantom. For three patients, 21 mg/kg unlabeled EF5 was administered after the PET scans, and tissue samples obtained the next day at surgery to determine EF5 binding using immunohistochemistry techniques (IHC). Results EF5 distributes evenly throughout soft tissue within minutes of injection. Its concentration in blood over the typical time frame of the study (~3.5 h) was nearly constant, consistent with a previously determined EF5 plasma half-life of ~13 h. Elimination was primarily via urine and bile. Radiation exposure from labeled EF5 is similar to other 18F-labeled imaging agents (e.g., FDG and FMISO). In a de novo glioblastoma multiforme patient, focal uptake of 18F-EF5 was confirmed by IHC. Conclusion These results confirm predictions of biodistribution and safety based on EF5's characteristics (high biological stability, high lipophilicity). EF5 is a novel hypoxia marker with unique pharmacological characteristics allowing both noninvasive and invasive measurements.