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Objective: To compare the diagnostic performance of three-dimensional (3D) positron emission mammography (PEM) versus whole body positron emission tomography (WBPET) for breast cancer. Methods: A total of 410 women with normal breast or benign or highly suspicious malignant tumors were randomized at 1 : 1 ratio to undergo 3D-PEM followed by WBPET or WBPET followed by 3D-PEM. Lumpectomy or mastectomy was performed on eligible participants after the scanning. Results: The sensitivity and specificity of 3D-PEM were 92.8% and 54.5%, respectively. WBPET showed a sensitivity of 95.7% and specificity of 56.8%. After exclusion of the patients with lesions beyond the detecting range of the 3D-PEM instrument, 3D-PEM showed higher sensitivity than WBPET (97.0% versus 95.5%, P = 0.913), particularly for small lesions (<1 cm) (72.0% versus 60.0%, P = 0.685). Conclusions: The 3D-PEM appears more sensitive to small lesions than WBPET but may fail to detect lesions that are beyond the detecting range. This study was approved by the Ethics Committee (E2012052) at the Tianjin Medical University Cancer Institute and Hospital (Tianjin, China). The instrument positron emission mammography (PEMi) was approved by China State Food and Drug Administration under the registration number 20153331166.

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To improve the stability of (18) F-labeled pyridaben analogs for myocardial perfusion imaging, three new analogs of pyridaben ([(18) F]FPTP2, [(18) F]FPTP-P2, and [(18) F]FPTP-P3) were synthesized with 'side chain' modifications. The radiolabeled tracers and corresponding non-radioactive compounds were obtained by substituting tosyl group with (18/19) F. The effect of structure modification on myocardial targeting and physicochemical properties of new tracers were evaluated in vitro and in vivo. The total radiosynthesis time of these tracers was approximately 70-90 min with high decay-corrected radiochemical yields (36-65%) and good radiochemical purity (> 98%). These lipophilic tracers exhibited obvious improved stability in water. Studies of their biodistribution in normal Kunming mice demonstrated that [(18) F]FPTP2 exhibited very high initial heart uptake (39.70 ± 2.81 %ID/g at 2 min after injection) and low background in the liver, blood, and soft tissues. The heart-to-liver, heart-to-lung, and heart-to-blood ratios were 3.59, 19.34, and 67.34 at 15 min postinjection, respectively. Favorable myocardial targeting property and remarkable improvement of stability of [(18) F]FPTP2 suggest that the substitution of the phenyl 'sidechain' with other non-phenyl rings has no effect on the myocardial targeting property of (18) F-labeled pyridaben analogs.

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INTRODUCTION: Cardiac myosin is a potential molecular target for heart failure imaging since its changes can be used to assess the function of heart. In this study, two analogues of Omecamtiv Mecarbil, which is the first selective activator of cardiac myosin, were synthesized and radio-labeled with (18)F. Then the radio-compounds were evaluated as potential cardiac myosin imaging agent. METHODS: The labeling precursor and the nonradioactive compounds were synthesized and characterized by IR, (1)H NMR, (13)C NMR and MS analysis. By substituting bromo of precursors with (18)F, the radiolabeled compounds [(18)F]8 and [(18)F]10 were prepared and further evaluated for their in vitro physicochemical properties, stabilities, protein binding assay and ex vivo biodistribution. RESULTS: Starting with [(18)F]F(-) Kryptofix 2.2.2./K2CO3 solution, the total reaction time for [(18)F]8 and [(18)F]10 was about 40 min respectively, with final high-performance liquid chromatography purification included. Typical decay-corrected radiochemical yield stayed at 12.47% ± 3.30% (n=8), the radiochemical purity, 98% or more. Their specific activity was estimated as 50 GBq/µmol. Both [(18)F]8 and [(18)F]10 could be stable after incubation in water at room temperature and in serum or binding buffer at 37 °C for 3h. Biodistribution in normal mice showed that both [(18)F]8 and [(18)F]10 have good heart uptake at 2 min post-injection time. Compound [(18)F]10 has better heart retention and higher heart to background ratios than those of [(18)F]8. In vitro protein binding assay demonstrates that [(18)F]10 may have high affinity with myosin from bovine heart. CONCLUSION: [(18)F]8 and [(18)F]10 were synthesized with good radiochemical yield and high radiochemical purity (>98%). One of the compounds ([(18)F]10) has higher bovine heart myosin binding affinity and better heart/liver ratio. It will be further evaluated as a potent cardiac myosin imaging agent in normal and systolic heart failure model with positron emission tomography in the future.

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UNLABELLED: In this study the (18)F-labeled pyridaben analogs 2-tertbutyl-4-chloro-5-(4-(2-(18)F-fluoroethoxy))benzyloxy-2H-pyridazin-3-one ((18)F-FP1OP) and 2-tertbutyl-4-chloro-5-(4-(2-(2-(2-(18)F-fluoroethoxy)ethoxy)ethoxy))benzyloxy-2H-pyridazin-3-one ((18)F-FP3OP) were synthesized, characterized, and evaluated as potential myocardial perfusion imaging (MPI) agents with PET. METHODS: The tosylate labeling precursors of 2-tert-butyl-4-chloro-5-(4-(2-tosyloxy-ethoxy))-benzyloxy-2H-pyridazin-3-one (OTs-P1OP), 2-tert-butyl-4-chloro-5-(4-(2-(2-(2-tosyloxy-ethoxy)ethoxy)ethoxy))-benzyloxy-2H-pyridazin-3-one (OTs-P3OP), and the corresponding nonradioactive compounds ((19)F-FP1OP and (19)F-FP3OP) were synthesized and characterized by infrared, (1)H nuclear magnetic resonance, (13)C nuclear magnetic resonance, and mass spectrometry analysis. (18)F-FP1OP and (18)F-FP3OP were obtained by 1-step nucleophilic substitution of tosyl with (18)F and evaluated as MPI agents in vitro (physicochemical properties, stability), ex vivo (autoradiography), and in vivo (toxicity and biodistribution in normal mice; cardiac PET in healthy Chinese mini swine and in acute myocardial infarction and chronic myocardial ischemia models). RESULTS: The total radiosynthesis time of both tracers, including final high-pressure liquid chromatography purification, was about 70-90 min. Typical decay-corrected radiochemical yields were about 50%, and the radiochemical purities were more than 98% after purification. (18)F-FP1OP had lower hydrophilicity and higher water stability than that of (18)F-FP3OP. In biodistribution studies, both (18)F-FP1OP and (18)F-FP3OP had high heart uptake (31.13 ± 6.24 and 31.10 ± 3.72 percentage injected dose per gram at 2 min after injection, respectively) and high heart-to-liver, heart-to-lung, and heart-to-blood ratios at all time points after injection. Further autoradiography evaluation of (18)F-FP1OP showed that the heart uptake could be blocked effectively by rotenone or nonradioactive (19)F-FP1OP. Clear cardiac PET images of (18)F-FP1OP were obtained in healthy Chinese mini swine at 2, 15, 30, 60, and 120 min after injection, and the uptake of perfusion deficit areas was much lower than in normal tissue in both acute myocardial infarction and chronic myocardial ischemia models. CONCLUSION: The (18)F-labeled pyridaben analogs reported in this study have high heart uptake and low background uptake in both the mouse model and the Chinese mini swine model. The tracer with the shorter radiolabeling side chain ((18)F-FP1OP) has better stability, faster clearance from the major organs, and a higher heart-to-liver ratio than the other tracer ((18)F-FP3OP). On the basis of the promising biologic properties, this mitochondrial complex I-targeted tracer ((18)F-FP1OP) is worthy to be developed as an MPI agent and to be compared with the other PET MPI agents in the future.

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Galactosylated chitosan (GC) was prepared by reacting lactobionic acid with water-soluble chitosan. GC was labeled with fluorine-18 by conjugation with N-succinimidyl-4-(18)F-fluorobenzoate ([(18)F]SFB) under a slightly basic condition. After rapid purification with HiTrap desalting column, [(18)F]FB-GC was obtained with high radiochemical purity (>97%) determined by radio-HPLC. The total reaction time for [(18)F]FB-GC was about 150 min. Typical decay-corrected radiochemical yield was about 4-8%. Ex vivo biodistribution in normal mice showed that [(18)F]FB-GC had moderate activity accumulation in liver with very good retention (11.13+/-1.63, 10.97+/-1.90 and 10.77+/-0.95%ID/g at 10, 60, 120 min after injection, respectively). The other tissues except kidney showed relative low radioactivity accumulation. The high liver/background ratio affords promising biological properties to get clear images. The specific binding of this radiotracer to the ASGP receptor was confirmed by blocking experiment in mice. Compared with the non-blocking group the hepatic uptake of [(18)F]FB-GC significantly declined in all selected time points. The better liver retention properties of [(18)F]FB-GC than that of albumin based imaging agents may improve imaging quality and simplify pharmacokinetic model of liver function in the future application with PET imaging.

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Using statistical parametric mapping (SPM), we evaluate the feasibility and accuracy of (18) F -2-deoxy-2-fluoro-D-glucose (FDG) positron emission tomography (PET) for clinical diagnosis with characteristic hypo-metabolic regions, and examine the consistency of cerebral hypo-metabolism in Alzheimer's disease (AD) cross multicenters at both the group and the individual levels. Four groups of scan data including 39 AD patients and 52 healthy control subjects derived from three centers were analyzed and comparisons between patient subgroups or individual patient and relevant control population were performed using Two Sample T-test. In the group analysis, the hypo-metabolic regions of AD patients obtained from different PET centers were similar and consistent. The common hypo-metabolic cerebral areas were located bilaterally in the posterior cingulate and medial parietal cortex, temporo-parietal cortex, prefrontal cortex, and the middle and inferior temporal gyrus (uncorrected, p<0.001). In the analysis of each individual subject, the location of declined posterior cingulate and medial parietal cortex, temporo-parietal cortex and temporal lobe were found highly consistent with relevant characteristic regions obtained in the group analysis and were selected for diagnostic purposes. Complete typical hypo-metabolic pattern was observed in 67% and 54% of AD patients in two sets of 3D scans, respectively. Only 27% and 33.3% patients showed full typical pattern in two sets of 2D scans. The results indicated that FDG PET measures and SPM can 4 provide a valuable reference for clinical diagnosis of AD patients. The potential influence of acquisition mode on the clinical diagnosis of AD was suggested for further evaluation.

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UNLABELLED: Myocardial extractions of pyridaben, a mitochondrial complex I (MC-I) inhibitor, is well correlated with blood flow. Based on the synthesis and characterization of pyridaben analogue 2-tert-butyl-5-[2-(2-[(18)F]fluroethoxy)ethoxy]benzyloxy]-4-chloro-2H-pyridazin-3-one ([(18)F]FP2OP), this study assessed its potential to be developed as myocardial perfusion imaging (MPI) agent. METHODS: The tosylate labeling precursor 2-(2-(4-(tert-butyl-5-chloro-6-oxo-1,6-dihydro-pyridazin-4-yloxymethyl)benzyloxy)ethoxy)ethyl ester (OTs-P2OP) and the nonradioactive 2-tert-butyl-5-[2-(2-[(19)F]fluroethoxy)ethoxy]benzyloxy]-4-chloro-2H-pyridazin-3-one ([(19)F]FP2OP) were synthesized and characterized by IR, (1)H NMR, (13)C NMR and MS analysis. By substituting tosyl of precursor OTs-P2OP with (18)F, the radiolabeled complex [(18)F]FP2OP was prepared and further evaluated for its in vitro physicochemical properties, in vivo biodistribution, the metabolic stability in mice, ex vivo autoradiography and cardiac PET/CT imaging. RESULTS: Starting with [(18)F]F(-) Kryptofix 2.2.2./K(2)CO(3) solution, the total reaction time for [(18)F]FP2OP was about 100 min, with final high-performance liquid chromatography purification included. Typical decay-corrected radiochemical yield stayed at 41+/-5.3%, the radiochemical purity, 98% or more. Biodistribution in mice showed that the heart uptake of [(18)F]FP2OP was 41.90+/-4.52%ID/g at 2 min post-injection time, when the ratio of heart/liver, heart/lung and heart/blood reached 6.83, 9.49 and 35.74, respectively. Lipophilic molecule was further produced by metabolized [(18)F]FP2OP in blood and urine at 30 min. Ex vivo autoradiography demonstrates that [(18)F]FP2OP may have high affinity with MC-I and that can be blocked by [(19)F]FP2OP or rotenone (a known MC-I inhibitor). Cardiac PET images were obtained in a Chinese mini-swine at 5, 15, 30 and 60 min post-injection time with high quality. CONCLUSION: [(18)F]FP2OP was synthesized with high radiochemical yield. The promising biological properties of [(18)F]FP2OP suggest high potential as MPI agent for positron emission tomography in the future.

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UNLABELLED: Asialoglycoprotein receptors (ASGP-R) are well known to exist on the mammalian liver, situate on the surface of hepatocyte membrane. Quantitative imaging of asialoglycoprotein receptors could estimate the function of the liver. (99m)Tc labeled galactosyl-neoglycoalbumin (NGA) and diethylenetriaminepentaacetic acid galactosyl human serum albumin (GSA) have been developed for SPECT imaging and clinical used in Japan. In this study, we labeled the NGA with (18)F to get a novel PET tracer [(18)F]FNGA and evaluated its hepatic-targeting efficacy and pharmacokinetics. METHODS: NGA was labeled with (18)F by conjugation with N-succinimidyl-4-(18)F-fluorobenzoate ([(18)F]SFB) under a slightly basic condition. The in vivo metabolic stability of [(18)F]FNGA was determined. Ex vivo biodistribution of [(18)F]FNGA and blocking experiment was investigated in normal mice. MicroPET images were acquired in rat with and without block at 5 min and 15 min after injection of the radiotracer (3.7MBq/rat), respectively. RESULTS: Starting with (18)F(-) Kryptofix 2.2.2./K(2)CO(3) solution, the total reaction time for [(18)F]FNGA is about 150 min. Typical decay-corrected radiochemical yield is about 8-10%. After rapid purified with HiTrap desalting column, the radiochemical purity of [(18)F]FNGA was more than 99% determined by radio-HPLC. [(18)F]FNGA was metabolized to produce [(18)F]FB-Lys in urine at 30 min. Ex vivo biodistribution in mice showed that the liver accumulated 79.18+/-7.17% and 13.85+/-3.10% of the injected dose per gram at 5 and 30 min after injection, respectively. In addition, the hepatic uptake of [(18)F]FNGA was blocked by pre-injecting free NGA as blocking agent (18.55+/-2.63%ID/g at 5 min pi), indicating the specific binding to ASGP receptor. MicroPET study obtained quality images of rat at 5 and 15 min post-injection. CONCLUSION: The novel ASGP receptor tracer [(18)F]FNGA was synthesized with high radiochemical yield. The promising biological properties of [(18)F]FNGA afford potential applications for assessment of hepatocyte function in the future. It may provide quantitative information and better resolution which particularly help to the liver surgery.

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This study reports the synthesis and characterization of N-(3-(4-(2-methoxyphenyl)piperazin-1-yl)propyl-4-[(18)F]fluorobenzamide ([(18)F]MPP3F). The total reaction time for [(18)F]MPP3F, including final high-performance liquid chromatography purification, was about 3h. Typical decay-corrected radiochemical yield was 18.4+/-3.1%. The radiochemical purity was >98%. Biodistribution in mice showed that [(18)F]MPP3F is a potential brain imaging agent for positron emission tomography. The brain uptake of [(18)F]MPP3F was 6.59+/-0.77% Injected Dose/g at 2 min post-injection time. A brain-to-blood ratio of 3.67 was reached at 15 min after injection.

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OBJECTIVE: To study the relationship between the scores of 3 neuropsychological scales: MMSE, extended scale of dementia (ESD) and Blessed dementia scale (BDS) and cerebral glucose metabolism in Alzheimer's disease (AD) indicated by positron emission tomography (PET). METHODS: Brain scanning was performed with SIEMENS ECAT 47 PET scanner among 21 AD patients, aged 60 - 83 (10 mild, 6 moderate, and 5 severe), and 15 healthy persons, aged 57 - 73. The ratio of mean radioactivity of cerebral lobe to that of cerebellum as semi-quantitative parameters was used to evaluate the cerebral glucose metabolism. Cognitive function was assessed by three neuropsycholigical scales: MMSE, ESD and BDS. RESULTS: The average MMSE score was 13.3 +/- 6.3 (range 2 - 25), the average ESD score was 120.5 +/- 54.8 (range 28 - 200), and the average BDS score was 4.7 +/- 3.1 (range 0.5 - 10) in the AD patients. The decreases of glucose metabolism in parietal, frontal and temporal lobes were significantly positively correlated with MMSE and ESD scores, and negatively correlated with BDS scores in AD patients (P < 0.05). The correlations between MMSE and ESD (r = 0.886), MMSE and BDS (r = -0.763), and ESD and BDS (r = -0.773) were significant in AD patients (all P < 0.01). Taking the ratio of radioactivity of cerebral lobe to that of cerebellum as an independent variable X, the MMSE, ESD and BDS scorsas dependent variable Y, three regression equations were established as follows: Y = 40.11 * X- 25.32, Y = 309.19 * X- 180.9, Y = 19.97 - 16.53 * X. The independent variable entering the three regression equations was always the ratio of radioactivity of left parietal lobe to that of cerebellum. The ratio of radioactivity of left parietal lobe to that of cerebellum was a significant predictor for cognitive dysfunction measured by MMSE, ESD and BDS in AD patients (P < 0.01). CONCLUSION: MMSE, ESD and BDS scores correlate well with impaired cerebral glucose metabolism in AD. The function of left parietal lobe may play an important role in the progress of the disease. MMSE, ESD and BDS are good measures for cognitive dysfunction.

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