Aprotic solvents are usually preferred for the SN2 reactions, because nucleophilicity and hence SN2 reactivity are severely retarded by the influence of the partial positive charge of protic solvents. In this work, we introduce a remarkable effect of using tertiary alcohols as a reaction medium for nucleophilic fluorination with alkali metal fluorides. In this novel synthetic method, the nonpolar protic tert-alcohol enhances the nucleophilicity of the fluoride ion dramatically in the absence of any kind of catalyst, greatly increasing the rate of the nucleophilic fluorination and reducing formation of byproducts (such as alkenes, alcohols, or ethers) compared with conventional methods using dipolar aprotic solvents. The great efficacy of this method is a particular advantage in labeling radiopharmaceuticals with [18F]fluorine (t1/2 = 110 min) for positron emission tomographic (PET) imaging, and it is illustrated by the synthesis of four [18F]fluoride-radiolabeled molecular imaging probes-[18F]FDG, [18F]FLT, [18F]FP-CIT, and [18F]FMISO-in high yield and purity and in shorter times compared to conventional syntheses.

Parkinson disease (PD), progressive supranuclear palsy (PSP), and multiple-system atrophy (MSA) are known to affect dopaminergic neurons of the brain stem and striatum with different preferential involvement. Here we investigated differences in striatal subregional dopamine transporter loss in PD, PSP, and MSA and assessed the diagnostic value of 18 F-fluorinated-N-3-fluoropropyl-2-b-carboxymethoxy-3-b-(4-iodophenyl)nortropane ( 18 F-FP-CIT) PET in differentiating PSP and MSA from PD. Methods: Forty-nine patients with PD, 19 patients with PSP, 24 patients with MSA, and 21 healthy people (healthy controls) were examined with 18 F-FP-CIT PET. The PET images were spatially normalized and analyzed with 12 striatal subregional volume-of-interest (VOI) templates (bilateral ventral striatum [VS], anterior caudate [AC], posterior caudate, anterior putamen, posterior putamen [PP], and ventral putamen [VP]) and 1 occipital VOI template. The nondisplaceable binding potential (BP ND ) and intersubregional ratio (ISR; defined as the ratio of the BP ND of one striatal subregion to that of another striatal subregion) of subregional VOIs were calculated. Results: The BP ND of all VOIs in the PD, MSA, and PSP groups were significantly lower than those in the healthy controls (P , 0.05). The BP ND of AC and the AC/VS ISR in the PSP group were significantly lower than those in the PD group. The BP ND of VP was significantly lower, but the PP/VP ISR was significantly higher in the MSA group than in the PD group. At the cutoff value for the AC/VS ISR (,0.7), the sensitivity and specificity for differentiating PSP from PD were 94% and 92%, respectively. At the cutoff value for the PP/VP ISR (.0.65), the sensitivity and specificity for differentiating MSA from PD were 90% and 45%, respectively. The diagnostic accuracy of visual analysis was similar to that of quantitative analysis for differentiating PSP from PD but was significantly higher for differentiating MSA from PD. Conclusion: Compared with PD, PSP and MSA showed more prominent and earlier dopamine transporter loss in the AC and VP, respectively. These findings could be useful for suggesting PSP or MSA in parkinsonian cases without characteristic atypical features.

SVaD without abnormal amyloid imaging was more common than expected. Patients with SVaD with and without abnormal amyloid imaging differed in clinical and MRI features, although there was considerable overlap.

[1] An accurate description of the irregularity region defined by a plasma bubble is critically important in understanding the dynamics of the region and its effects on radio scintillation. Here we describe a plasma depletion region as a ''depletion shell'' and show how two-dimensional optical images from space can be used to define the shape of the depletion shell. Our simple model calculation demonstrates that the space-based optical observation can detect the plasma-depleted magnetic flux tubes only near the F-peak height. The backward C-shape in bubble images from optical observations is the trace of the plasma depletion shell near the F-peak height. The westward tilt of bubbles at the magnetic equator can also be explained by this shell structure. The in situ measurement of the ion velocity at night in the topside shows the decrease of the eastward plasma drift with an increase of latitude. The formation of the plasma depletion shell is consistent with the latitudinal/altitudinal shear in the zonal plasma flow.

Purpose: (4S)-4-(3-[18F]fluoropropyl)-l-glutamate (BAY 94-9392, alias [18F]FSPG) is a new tracer to image xC− transporter activity with positron emission tomography (PET). We aimed to explore the tumor detection rate of [18F]FSPG in patients relative to 2-[18F]fluoro-2-deoxyglucose ([18F]FDG). The correlation of [18F]FSPG uptake with immunohistochemical expression of xC− transporter and CD44, which stabilizes the xCT subunit of system xC−, was also analyzed. Experimental Design: Patients with non–small cell lung cancer (NSCLC, n = 10) or breast cancer (n = 5) who had a positive [18F]FDG uptake were included in this exploratory study. PET images were acquired following injection of approximately 300 MBq [18F]FSPG. Immunohistochemistry was done using xCT- and CD44-specific antibody. Results: [18F]FSPG PET showed high uptake in the kidney and pancreas with rapid blood clearance. [18F]FSPG identified all 10 NSCLC and three of the five breast cancer lesions that were confirmed by pathology. [18F]FSPG detected 59 of 67 (88%) [18F]FDG lesions in NSCLC, and 30 of 73 (41%) in breast cancer. Seven lesions were additionally detected only on [18F]FSPG in NSCLC. The tumor-to-blood pool standardized uptake value (SUV) ratio was not significantly different from that of [18F]FDG in NSCLC; however, in breast cancer, it was significantly lower (P < 0.05). The maximum SUV of [18F]FSPG correlated significantly with the intensity of immunohistochemical staining of xC− transporter and CD44 (P < 0.01). Conclusions: [18F]FSPG seems to be a promising tracer with a relatively high cancer detection rate in patients with NSCLC. [18F]FSPG PET may assess xC− transporter activity in patients with cancer. Clin Cancer Res; 18(19); 5427–37. ©2012 AACR.

Purpose: To evaluate the usefulness of 3 ¶-deoxy-3 ¶-[18 F]fluorothymidine (FLT)-positron emission tomography (PET) for predicting response and patient outcome of gefitinib therapy in patients with adenocarcinoma of the lung. Experimental Design: Nonsmokers with advanced or recurrent adenocarcinoma of the lung were eligible. FLT-PET images of the thorax were obtained before and 7 days after the start of gefitinib (250 mg/d) therapy, the maximum standardized uptake values (SUVmax) of primary tumors were measured, and the percent changes in SUVmax were calculated. After 6 weeks of therapy, the responses were assessed by computed tomography of the chest. Results: Among 31 patients who were enrolled, we analyzed 28 patients for whom we had complete data. Chest computed tomography revealed partial response in 14 (50%), stable disease in 4 (14%), and progressive disease in 10 (36%) after 6 weeks of treatment. Pretreatment SUVmax of the tumors did not differ between responders and nonresponders. At 7 days after the initiation of therapy, the percent changes in SUVmax were significantly different (-36.0 F 15.4% versus 10.1 F 19.5%; P < 0.001). Decrease of >10.9% in SUVmax was used as the criterion for predicting response. The positive and negative predictive values were both 92.9%. The time to progression was significantly longer in FLT-PET responders than nonresponders (median, 7.9 versus 1.2 months; P = 0.0041). Conclusion: FLT-PETcan predict response to gefitinib 7 days after treatment in nonsmokers with advanced adenocarcinoma of the lung.The change in tumor SUVmax obtained by FLT-PETseems to be a promising predictive variable.Morphologic imaging techniques such as computed tomography (CT) have been standard methods for assessing tumor response to treatment. Changes in size, however, are often delayed; hence, morphologic imaging is usually repeated after at least 6 weeks of therapy. This causes difficulties in assessing the early treatment response and hinders rapid decisions by clinicians regarding a change in therapy for nonresponders. Moreover, in the case of cytostatic agents, tumors may not regress radiologically despite effective treatment. These limitations could be overcome by using functional imaging techniques such as positron emission tomography (PET), because metabolic and physiologic changes in the tumor are likely to precede changes in size (1). The most widely used PET tracer is [18 F]fluorodeoxyglucose (FDG), which reflects cell metabolism. However, FDG is not highly tumor specific and is also taken up by inflammatory cells such as macrophages (2).Recently, 3 ¶-deoxy-3 ¶-[ 18 F]fluorothymidine (FLT) was introduced as a PET tracer for imaging tumor proliferation. FLT is phosphorylated by thymidine kinase 1, the key enzyme of the salvage pathway of DNA synthesis, and then trapped in the cell with little further metabolism (3). Thymidine kinase 1 is selectively up-regulated during the S phase of the cell cycle (4). Therefore, FLT uptake is dependent on cell proliferation. In lung tumors, FLT up...

Our findings suggest that although deep CMBs are mainly linked to subcortical SVD, both subcortical SVD and amyloid-related pathologies (eg, CAA) contribute to the pathogenesis of lobar CMBs, at least in subjects with mixed lobar and deep CMBs. Furthermore, subcortical SVD and amyloid-related pathologies interact to increase the risk of lobar CMBs.

These findings indicate that FLT PET is useful for evaluating tumor grade and cellular proliferation in brain tumors. It displayed high sensitivity and good contrast in evaluating brain lesions that showed similar or decreased uptake compared with normal gray matter on FDG PET. FLT PET, however, did not appear to be sufficiently useful for differentiating tumors from nontumorous lesions.