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1.
《International journal of radiation applications and instrumentation. Part B, Nuclear medicine and biology》1992,19(2):167-173
11,17β-Dihydroxy-6-methyl-17α -(3-[18F]fluoro-prop-1 -ynyl)androsta-1,4,6-trien-3-one ([18F]RU 52461), an 18F-analog of RU 28362, was synthesized by bromide displacement with [18F]fluoride in 12–30% overall radiochemical yield (decay-corrected) within 140 min from end of bombardment (EOB). The specific activity was 900–1500 mCi/μmol (33.3–55.5 GBq/μmol) at the end of synthesis (EOS). Biodistribution studies indicated high adrenal and pituitary retention, and uniformly low uptake of [18F]RU 52461 in all other brain regions of the rat. Except for the pituitary, no specific receptor-mediated uptake of [18F]RU 52461 could be demonstrated using saturating doses of unlabeled RU 52461 in rat brain. While no change was observed throughout the brain areas in adrenalectomized rats and in animals coinjected with dexamethasone, when compared to controls. PET studies revealed extremely low levels of radioactivity in baboon brain. Therefore, [18F]RU 52461 does not appear to cross the blood-brain barrier, suggesting that this radiopharmaceutical is not suitable to visualize the brain glucocorticoid binding sites by PET. 相似文献
2.
Xinmiao Lu Cheng Wang Xiao Li Peilin Gu Lina Jia Lan Zhang 《Bioorganic & medicinal chemistry》2019,27(3):545-551
Epidermal growth factor receptor (EGFR) has emerged as an attracting target in the field of imaging and treatment for non-small cell lung cancer (NSCLC). Radiolabeled EGFR-tyrosine kinase inhibitors (EGFR-TKIs) specifically targeting EGFR are deemed as promising probes for the imaging of NSCLC. This study aimed to label icotinib (one kind of EGFR-TKI) with 18F through click reaction to develop a new EGFR-targeting PET probe-18F-icotinib. 18F-icotinib was obtained in 44.81% decay-corrected yield in 100?min synthesis time with 34?GBq/μmol specific activity and >99% radiochemical purity at the end of synthesis. The identity of the product was confirmed by co-injection with 18F-icotinib and 19F-icotinib. The Log P was 1.28?±?0.04 (n?=?6). The tracer displayed excellent stability after incubation for 4?h in vitro. 18F-icotinib showed satisfying binding ability to A549 NSCLC cells, which could be inhibited by icotinib. PET imaging studies demonstrated a specific uptake of the radiotracer (0.90?±?0.24% ID/g) in A549 tumor-bearing mice, while lower uptake was observed in heart, lung and spleen at 1.5?h post injection. Inmunohistochemical staining confirmed that the A549 tumor was EGFR-positive. Therefore, we considered that 18F-icotinib was a highly promising compound for EGFR-based tumor PET imaging. 相似文献
3.
~(18)F-FDG PET/CT常规代谢成像反应肿瘤的葡萄糖代谢及乏氧情况,而~(18)F-FDG PET/CT早期动态成像能反映PET/CT成像早期肿瘤的灌注情况。由于肿瘤的异质性,在早期动态~(18)F-FDG PET/CT成像,即~(18)F-FDG PET/CT灌注成像中,存在独立于常规60 min~(18)F-FDG PET/CT代谢成像的SUVmax(最大标准摄取值)高摄取区。因此,在临床工作中应用~(18)F-FDG PET/CT早期动态成像,能够进一步对实体肿瘤的活性区域进行评估,能够更好评价患者预后、完善治疗方案。当前~(18)F-FDG早期动态成像已经应用在肝癌、肾癌以及膀胱癌等实体肿瘤诊断中。早期动态~(18)F-FDG PET/CT成像结合常规标准~(18)F-FDG PET/CT代谢成像,对实体肿块进行一站式成像方法,能够更好的对肿瘤进行评估。 相似文献
4.
Changning Wang Christian K. Moseley Stephen M. Carlin Colin M. Wilson Ramesh Neelamegam Jacob M. Hooker 《Bioorganic & medicinal chemistry letters》2013,23(11):3389-3392
EMPA is a selective antagonist of orexin 2 (OX2) receptors. Previous literature with [3H]-EMPA suggest that it may be used as an imaging agent for OX2 receptors; however, brain penetration is known to be modest. To evaluate the potential of EMPA as a PET radiotracer in non-human primate (as a step to imaging in man), we radiolabeled EMPA with carbon-11. Radiosynthesis of [11C]N-ethyl-2-(N-(6-methoxypyridin-3-yl)-2-methylphenylsulfonamido)-N-(pyridin-3-ylmethyl)acetamide ([11C]EMPA), and evaluation as a potential PET tracer for OX2 receptors is described. Synthesis of an appropriate non-radioactive O-desmethyl precursor was achieved from EMPA with sodium iodide and chlorotrimethylsilane. Selective O-methylation using [11C]CH3I in the presence of cesium carbonate in DMSO at room temp afforded [11C]EMPA in 1.5–2.5% yield (non-decay corrected relative to trapped [11C]CH3I at EOS) with ?95% chemical and radiochemical purities. The total synthesis time was 34–36 min from EOB. Studies in rodent suggested that uptake in tissue was dominated by nonspecific binding. However, [11C]EMPA also showed poor uptake in both rats and baboon as measured with PET imaging. 相似文献
5.
S-11C-methyl-l-cysteine (LMCYS) is an attractive amino acid tracer for clinical tumor positron emission tomography (PET) imaging. d-isomers of some radiolabeled amino acids are potential PET tracers for tumor imaging. In this work, S-11C-methyl-d-cysteine (DMCYS), a d-amino acid isomer of S-11C-methyl-cysteine for tumor imaging was developed and evaluated. DMCYS was prepared by 11C-methylation of the precursor d-cysteine, with an uncorrected radiochemical yield over 50 % from 11CH3I within a total synthesis time from 11CO2 about 12 min. In vitro competitive inhibition studies showed that DMCYS uptake was primarily transported through the Na+-independent system L, and also the Na+-dependent system B0,+ and system ASC, with almost no system A. In vitro incorporation experiments indicated that almost no protein incorporation was found in Hepa 1–6 hepatoma cell lines. Biodistribution studies demonstrated higher uptake of DMCYS in pancreas and liver at 5 min post-injection, relatively lower uptake in brain and muscle, and faster radioactivity clearance from most tissues than those of l-isomer during the entire observation time. In the PET imaging of S180 fibrosarcoma–bearing mice and turpentine-induced inflammatory model mice, 2-18F-fluoro-2-deoxy-d-glucose (FDG) exhibited significantly high accumulation in both tumor and inflammatory lesion with low tumor-to-inflammation ratio of 1.40, and LMCYS showed low tumor-to-inflammation ratio of 1.64 at 60 min post-injection. By contrast, DMCYS showed moderate accumulation in tumor and very low uptake in inflammatory lesion, leading to relatively higher tumor-to-inflammation ratio of 2.25 than 11C-methyl-l-methionine (MET) (1.85) at 60 min post-injection. Also, PET images of orthotopic transplanted glioma models demonstrated that low uptake of DMCYS in normal brain tissue and high uptake in brain glioma tissue were observed. The results suggest that DMCYS is a little better than the corresponding l-isomers as a potential PET tumor-detecting agent and is superior to MET and FDG in the differentiation of tumor from inflammation. 相似文献
6.
Katsushi Kumata Yiding Zhang Masayuki Fujinaga Takayuki Ohkubo Wakana Mori Tomoteru Yamasaki Masayuki Hanyu Lin Xie Akiko Hatori Ming-Rong Zhang 《Bioorganic & medicinal chemistry》2018,26(17):4817-4822
DAA1106 (N-(2,5-dimethoxybenzyl)-N-(5-fluoro-2-phenoxyphenyl)acetamide), is a potent and selective ligand for the translocator protein (18?kDa, TSPO) in brain mitochondrial fractions of rats and monkey (Ki?=?0.043 and 0.188?nM, respectively). In this study, to translate [18F]DAA1106 for clinical studies, we performed automated syntheses of [18F]DAA1106 using the spirocyclic iodonium ylide (1) as a radiolabelling precursor and conducted preclinical studies including positron emission tomography (PET) imaging of TSPO in ischemic rat brains. Radiofluorination of the ylide precursor 1 with [18F]F?, followed by HPLC separation and formulation, produced the [18F]DAA1106 solution for injection in 6% average (n?=?10) radiochemical yield (based on [18F]F?) with >98% radiochemical purity and molar activity of 60–100?GBq/μmol at the end of synthesis. The synthesis time was 87?min from the end of bombardment. The automated synthesis achieved [18F]DAA1106 with sufficient radioactivity available for preclinical and clinical use. Biodistribution study of [18F]DAA1106 showed a low uptake of radioactivity in the mouse bones. Metabolite analysis showed that >96% of total radioactivity in the mouse brain at 60?min after the radiotracer injection was unmetabolized [18F]DAA1106. PET study of ischemic rat brains visualized ischemic areas with a high uptake ratio (1.9?±?0.3) compared with the contralateral side. We have provided evidence that [18F]DAA1106 could be routinely produced for clinical studies. 相似文献
7.
Mingzhang Gao Min Wang Kathy D. Miller Gary D. Hutchins Qi-Huang Zheng 《Bioorganic & medicinal chemistry》2010,18(6):2099-2106
Cannabinoids have been recently proposed as a new family of potential antitumor agents, and cannabinoid receptor 2 (CB2) is believed to be over-expressed in tumor cells. This study was designed to develop new radioligands for imaging of CB2 receptor in cancer using biomedical imaging technique positron emission tomography (PET). Carbon-11-labeled 2-oxoquinoline and 2-chloroquinoline derivatives, [11C]6a–d and [11C]9a–d, were prepared by O-[11C]methylation of their corresponding precursors using [11C]CH3OTf under basic conditions and isolated by a simplified solid-phase extraction (SPE) method in 40–50% radiochemical yields based on [11C]CO2 and decay corrected to end of bombardment (EOB). The overall synthesis time from EOB was 15–20 min, the radiochemical purity was >99%, and the specific activity at end of synthesis (EOS) was 111–185 GBq/μmol. Radioligand binding assays indicated compounds 6f, 6b, and 9f display potent in vitro binding affinities with nanomolar Ki values and at least 100–2000-fold selectivity for CB2. 相似文献
8.
PurposeA standardized method for quantification is required for analyzing PET data, but such standards have not been established for tau PET imaging. The Centiloid scale has recently been proposed as a standard method for quantifying amyloid deposition on PET imaging. Therefore, the present study aimed to apply the Centiloid scale to 18F-THK5351 PET imaging in Alzheimer’s disease (AD).MethodsWe acquired 18F-THK5351 PET, 11C-PiB PET, and MR images from 47 cognitively normal (CN) individuals and 28 patients with AD with mild to moderate dementia. PET images were spatially normalized to Montreal Neurological Institute space. The PET signals were then normalized using the signal in the reference volume of interest (VOI). Target VOI for specific 18F-THK5351 retention in AD was extracted by voxel-wise comparison of PET images between the 47 CN individuals and 16 AD patients with moderate dementia. Scale anchor points were defined by the CN individuals as 0-anchor points and by that of the average of the typical AD patients as 100-anchor points.ResultsSpecific retention of 18F-THK5351 was predominant in the angular gyrus, inferior temporal cortex, and parieto-occipital regions in patients with AD. Standardized uptake value ratio (SUVR) of 1.227 and 1.797 were defined as 0- and 100-anchor points, respectively. 18F-THK5351 PET data could be expressed using the Centiloid scale, with the SUVR of the 18F-THK5351 PET images converted to Centiloid using our VOI, the standard Centiloid reference VOI, and the following equation: Centiloid = 169.0 × SUVR–204.6.ConclusionCentiloid methods can be applied to tau PET imaging using 18F-THK5351. 相似文献
9.
M. Zuhayra A. Alfteimi C. Von Forstner U. Lützen B. Meller E. Henze 《Bioorganic & medicinal chemistry》2009,17(21):7441-7448
O-(2-[18F]fluoroethyl)-l-tyrosine ([18F]FET) is one of the first 18F-labeled amino acids for imaging amino acid metabolism in tumors. This tracer overcomes the disadvantages of [18F]fluorodeoxyglucose, [18F]FDG, and [11C]methionine, [11C]MET. Nevertheless, the various synthetic methods providing 18F[FET] exhibit a big disadvantage concerning the necessity of two purification steps during the synthesis including HPLC purification, which causes difficulties in the automation, moderate yields, and long synthesis times >60 min.A new approach for the synthesis of [18F]FET is developed starting from 2-bromoethyl triflate as precursor. After optimization of the synthesis parameters including the distillation step of [18F]-FCH2CH2Br combined with the final purification of [18F]FET using a simple solid phase extraction instead of an HPLC run the synthesis [18F]FET could be significantly simplified, shortened, and improved. The radiochemical yield (RCY) was about 45% (not decay corrected and calculated relative to [18F]F− activity that was delivered from the cyclotron). Synthesis time was only 35 min from the end of bombardment (EOB) and the radiochemical purity was >99% at the end of synthesis (EOS). Thus, this simplified synthesis for [18F]FET offers a very good option for routine clinical use. 相似文献
10.
《Bioorganic & medicinal chemistry letters》2020,30(12):127187
The asialoglycoprotein receptor (ASGPR) is abundantly expressed on the surface of hepatocytes where it recognizes and endocytoses glycoproteins with galactosyl and N-acetylgalactosamine groups. Given its hepatic distribution, the asialoglycoprotein receptor can be targeted by positron imaging agents to study liver function using PET imaging. In this study, the positron imaging agent [18F]FPGal was designed to specifically target hepatic asialoglycoprotein receptor and its effectiveness was assessed in in vitro and in vivo models. The radiosynthesis of [18F]FPGal required 50 min with total radiochemical yields of [18F]FPGal from [18F]fluoride as 10% (corrected radiochemical yield). The Kd of [18F]FPGal to ASGPR in HepG2 cells was 1.99 ± 0.05 mM. Uptake values of 0.55% were observed within 30 min of incubation with HepG2 cells, which could be blocked by 200 mM d(+)-galactose (<0.1%). In vivo biodistribution analysis showed that the liver accumulation of [18F]FPGal at 30 min was 4.47 ± 0.96% ID/g in normal mice compared to 1.33 ± 0.07% ID/g in hepatic fibrotic mice (P < 0.01). Reduced uptake in the hepatic fibrosis mouse models was confirmed through PET/CT images at 30 min. Compared to normal mice, the standard uptake value (SUV) in the hepatic fibrosis mice was significantly lower when assessed through dynamic data collection for 1 h. Therefore, [18F]FPGal is a feasible PET probe that provide insight into ASGPR related liver disease. 相似文献
11.
New complexes LnI2·18-crown-6 (Ln-Sm, Tm, Dy, Nd) and LnJ2·dibenzo-18-crown-6 (Ln-Sm, Tm) were synthesized using the solutions of LnI2 in THF. The compounds obtained oxidize quickly in air, but are relatively stable in an inert atmosphere. The Tm2+ complex is decomposed by light. The compounds obtained are poorly soluble in THF, the Sm2+ and Tm2+ compounds are soluble in CH3CN, forming solutions with a period of half oxidation of 170 h and 6 min, respectively. Iodide ions of the complexes can be substituted for Cl? during treatment of the compounds by solution of LiCl in THF. The reflection spectra of the compounds synthesized are similar to the absorption spectra of Ln2+ in THF, although a shift of bands towards the short wave region is observed.The study of the Ln2+ oxidation kinetics in H2O, CH3CN, THF in the presence of crown ethers has shown that their stability is influenced not only by the type of solvent, relative solubility and stability of complexes Ln2+ and Ln3+, but also by phenyl groups, and by decreasing stability of Dy2+ and Nd2+. 相似文献
12.
Purpose[18F]Fluoromethylcholine ([18F]FMCH) is a radiopharmaceutical used in positron emission tomography (PET) imaging for the study of prostate, breast, and brain tumors. It is usually synthesized in cyclotron facilities where 18F is produced by proton irradiation of [18O]H2O through 18O(p,n)18F reaction. Due to the activation of target materials, the bombardment causes unwanted radionuclidic impurities in [18O]H2O, that need to be removed during the radiopharmaceutical synthesis. Thus, the aim of this study is to quantify the radionuclide impurities in the 18F production process and in the synthesized [18F]FMCH, demonstrating the radionuclidic purity of this radiopharmaceutical.MethodsLong-lived radionuclide impurities were experimentally assessed using high-resolution gamma and liquid scintillation spectrometries, while short-lived impurities were monitored analyzing the decay curve of the irradiated [18O]H2O with an activity calibrator. As spectrometric radionuclide library, a Geant4 Monte Carlo simulation of the 18F-target assembly was previously performed.Results3H, 52,54Mn, 56,57,58Co, 95m,96Tc, 109Cd, and 184Re were found in the irradiated [18O]H2O, but no radionuclide was found in the non-irradiated [18O]H2O neither in the final [18F]FMCH solution with an activity concentration greater than the minimum detectable activity concentration. A total impurity activity <6.2 kBq was measured in the irradiated [18O]H2O, whereas a [18F]FMCH radionuclide purity >99.9999998% was estimated. Finally, the decay curve of the irradiated [18O]H2O revealed a very low maximum of 13N activity (<0.03% of 18F) even immediately after the end of bombardment.ConclusionsThis study demonstrated the radionuclidic purity of [18F]FMCH according to the EU Pharmacopeia. 相似文献
13.
Photoirradiation with a 150 W medium-pressure Hg lamp for 17 h in acetontrile as the solvent replaces the benzene ligand in the cationic complexes [(η6-C6H6)Ru(CH3CN)2(L)]2+ and [(η6-C6H6)Ru(CH3CN)(L2)]2+ (L=CH3CN, PPh3, L2=dppe, bipy) with acetonitrile. These replacements are equally clean to those reported before for analogous CpRu+ complexes. Crystal structures of the products obtained are included. 相似文献
14.
《Bioorganic & medicinal chemistry letters》2020,30(2):126785
Altered dynamics of microtubules (MT) are implicated in the pathophysiology of a number of brain diseases. Therefore, radiolabeled MT targeted ligands that can penetrate the blood brain barrier (BBB) may offer a direct and sensitive approach for diagnosis, and assessing the clinical potential of MT targeted therapeutics using PET imaging. We recently reported two BBB penetrating radioligands, [11C]MPC-6827 and [11C]HD-800 as specific PET ligands for imaging MTs in brain. The major metabolic pathway of the above molecules is anticipated to be via the initial labeling site, O-methyl, compared to the N-methyl group. Herein, we report the radiosynthesis of N-11CH3-MPC-6827 and N-11CH3-HD-800 and a comparison of their in vivo binding with the corresponding O-11CH3 analogues using microPET imaging and biodistribution methods. Both O-11CH3 and N-11CH3 labeled MT tracers exhibit high specific binding and brain. The N-11CH3 labeled PET ligands demonstrated similar in vivo binding characteristics compared with the corresponding O-11CH3 labeled tracers, [11C]MPC-6827 and [11C]HD-800 respectively. 相似文献
15.
《International journal of radiation applications and instrumentation. Part B, Nuclear medicine and biology》1989,16(7):741-746
Sodium thiocyanate (NaSCN) was labelled with carbon-11 for in vivo studies of anion kinetics using positron emission tomography (PET). The synthesis was complete in 35 min from end of bombardment using [11Qammonium cyanide as the labelled precursor. [11C]NaSCN was produced by the reaction of [11C]sodium cyanide with elemental sulfur and subsequently separated by semi-preparative high performance liquid chromatography (HPLC). Radiochemical yields (isolated) were of the order of 25%. The specific activity was 18 GBq/mmol and the radiochemical purity better than 99%. A PET study performed in a healthy volunteer showed distribution of [11C]SCN− to areas corresponding to cortical fluid spaces known to be accessible to inorganic ions such as Cl−. An accumulation of the tracer was observed during the 70 min investigation, indicating at least three compartments of distribution. 相似文献
16.
Hao-Wen Kao Chuan-Lin Chen Wen-Yi Chang Jenn-Tzong Chen Wuu-Jyh Lin Ren-Shyan Liu Hsin-Ell Wang 《Bioorganic & medicinal chemistry》2013,21(4):912-921
Quantification of the expression of asialoglycoprotein receptor (ASGPR), which is located on the hepatocyte membrane with high-affinity for galactose residues, can help assess ASGPR-related liver diseases. A hepatic fibrosis mouse model with lower asialoglycoprotein receptor expression was established by dimethylnitrosamine (DMN) administration. This study developed and demonstrated that 4-18F-fluoro-N-(6-((3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)oxy)hexyl)benzamide (18F-FBHGal), a new 18F-labeled monovalent galactose derivative, is an asialoglycoprotein receptor (ASGPR)-specific PET probe in a normal and a hepatic fibrosis mouse models. Immunoassay exhibited a linear correlation between the accumulation of GalH-FITC, a fluorescent surrogate of FBHGal, and the amount of ASGPR. A significant reduction in HepG2 cellular uptake (P <0.0001) was observed using confocal microscopy when co-incubated with 0.5 μM of asialofetuin, a well known ASGPR blocking agent. Animal studies showed the accumulation of 18F-FBHGal in fibrosis liver (14.84 ± 1.10 %ID/g) was appreciably decreased compared with that in normal liver (20.50 ± 1.51 %ID/g, P <0.01) at 30 min post-injection. The receptor indexes (liver/liver-plus-heart ratio at 30 min post-injection) of hepatic fibrosis mice derived from both microPET imaging and biodistribution study were significantly lower (P <0.01) than those of normal mice. The pharmacokinetic parameters (T1/2α, T1/2β, AUC and Cl) derived from microPET images revealed prolonged systemic circulation of 18F-FBHGal in hepatic fibrosis mice compared to that in normal mice. The findings in biological characterizations suggest that 18F-FBHGal is a feasible agent for PET imaging of hepatic fibrosis in mice and may provide new insights into ASGPR-related liver dysfunction. 相似文献
17.
S. John Gatley Ding-Wei Yu Joanna S. Fowler Robert R. MacGregor David J. Schlyer Stephen L. Dewey Alfred P. Wolf Thomas Martin Colleen E. Shea Nora D. Volkow 《Journal of neurochemistry》1994,62(3):1154-1162
Abstract: The psychostimulant drug of abuse, cocaine (benzoylecgonine methyl ester), is rapidly metabolized by cleavage of its two ester groups, to give benzoylecgonine (BE) and ecgonine methyl ester, and by N-demethylation, to give N-norcocaine (NC). The recent use of [N-methyl-11CH3]cocaine to image brain cocaine binding sites with positron emission tomography (PET) raises the question of whether PET images partially reflect the distribution and kinetics of labeled cocaine metabolites. We prepared [O-metty/-11CH3]cocaine by methylation of the sodium salt of BE with [11C]CH3l, and showed that PET baboon brain scans, as well as regional brain kinetics and plasma time-activity curves corrected for the presence of labeled metabolites, are nearly identical to those seen with [N-methyl-11CH3]cocaine. This strongly suggests that 11C metabolites do not significantly affect PET images, because the metabolite pattern is different for the two labeled forms of cocaine. In particular, nearly half the 11C in blood plasma at 30 min was [11C]CO2 when [N-methy/-11CH3]cocaine was administered, whereas [11C]CO2 was not formed from [O-methy/-11CH3]cocaine. Only a trace of [11C]NC was detected in plasma after [O-methyl-11CH3]cocaine administration. Nearly identical brain PET data were also obtained when 4′-[N-methy/-11CH3]fluorococaine and 4′-[18F]fluoro-cocaine (prepared by nucleophilic aromatic substitution from [18F]fluoride-and 4′-nitrococaine) were compared with [N-methy/-11CH3]cocaine. In vitro assays with rat brain membranes showed that cocaine and 4′-fluoroco-caine were equipotent at the dopamine reuptake site, but that 4′-fluorococaine was about 100 times more potent at the 5-hydroxytryptamine reuptake site. The studies with positron-emitting 4′-fluorococaines thus support the lack of significance of labeled metabolites or of binding to 5-hydroxytryptamine reuptake sites to PET images taken with [N-methy/-11CH3]cocaine. [11C]NC prepared by O-methylation of norbenzoylecgonine gave PET images with preferential uptake in striatum, but slower clearance from all brain regions than [O-methy/-11CH3]cocaine. [11C]BE prepared by N-methylation of norbenzoylecgonine did not show brain uptake. 相似文献
18.
Miguel Cortijo Ángela Valentín-Pérez Patrick Rosa Nicolas Daugey Thierry Buffeteau Elizabeth A. Hillard 《Chirality》2020,32(6):753-764
It has been recently shown that enantiomers of the helicoidal paddlewheel complex [Co3(dpa)4(CH3CN)2]2+ (dpa = the anion of 2,2′-dipyridylamine) can be resolved using the chiral [As2(tartrate)2]2− anion (AsT) and that these complexes demonstrate a strong chiroptical response in the ultraviolet-visible and X-ray energy regions. Here we report that the nickel congener, [Ni3(dpa)4(CH3CN)2]2+, can likewise be resolved using AsT. Depending on the stereochemistry of the enantiopure AsT anion, one or the other of the trinickel enantiomers crystallize from CH3CN and diethyl ether in space group P4212 as the (NBu4)2[Ni3(dpa)4(CH3CN)2](AsT)2·[solvent] salt. After resolution, the AsT salts were converted into the PF6− salts by anion exchange, with retention of the chirality of the trinickel complex. The enantiopure [Ni3(dpa)4(CH3CN)2](PF6)2·2CH3CN and [Co3(dpa)4(CH3CN)2](PF6)2·CH3CN·C4H10O compounds crystallize in space groups C2 and P21, respectively. Both the Ni(II) and Co(II) complex cations are stable towards racemization in CH3CN. Vibrational circular dichroism (VCD) data obtained in CD3CN demonstrate the expected mirror image spectra for the enantiomers, the observed peaks arising from the dpa ligand. The VCD response is significant, with Δε values up to 6 Lmol−1 cm−1 and vibrational dissymmetry factors on the order of 10−3. Density functional theory calculations well reproduce the experimental spectra, showing little difference between the peak position, sign, and intensity in the VCD for the cobalt and nickel complexes. These results suggest that VCD enhancement of these peaks is unlikely, and their remarkable intensity may be due to their rigid helicoidal structure. 相似文献
19.
Huailei Jiang Aditya Bansal Ribu Goyal Kah-Whye Peng Stephen J. Russell Timothy R. DeGrado 《Bioorganic & medicinal chemistry》2018,26(1):225-231
Noninvasive imaging of iodide uptake via the sodium/iodide symporter (NIS) has received great interest for evaluation of thyroid cancer and reporter imaging of NIS-expressing viral therapies. In this study, we investigate 18F-labeled hexafluorophosphate (HFP or PF6?) as a high-affinity iodide analog for NIS imaging. 18F-HFP was synthesized by radiofluorination of phosphorus pentafluoride·N-methylpyrrolidine complex and evaluated in human NIS (hNIS)-expressing C6 glioma cells and a C6 glioma xenograft mouse model. 18F-HFP was obtained in radiochemical yield of 10?±?5%, radiochemical purity of >96% and specific radioactivity of 604?±?18?MBq/µmol. Specific uptake of 18F-HFP and high affinity of 19F-HFP were observed in hNIS+ C6-glioma cells. PET imaging showed robust uptake of 18F-HFP in NIS-expressing tissues (thyroid, stomach, and hNIS+ C6 glioma xenografts), and the uptake of 18F-HFP was blocked by NaClO4 pretreatment. Specific accumulation in hNIS-expressing xenograft (hNIS+) was observed relative to isogenic control tumor (hNIS?). Clearance of 18F-HFP was predominantly through renal excretion. The biodistribution showed consistent results with PET imaging. Minimal bone uptake was observed over 2?h period post-injection, indicating excellent in vivo stability of 18F-HFP. Although improvement in specific radioactivity is desirable, the results indicate that 18F-HFP is a promising candidate radiotracer for further evaluation for NIS imaging. 相似文献
20.
V. Huchet F. Paycha S. Balogova A. Halimi K. Kerrou O. Pascal F. Montravers J.-N. Talbot 《Médecine Nucléaire》2009,33(7):388-397
Fluorodeoxyglucose (18F) or FDG, the radioactive glucose analogue which is the reference radiopharmaceutical in oncologic PET, is not well suited for the detection of prostate cancer metastases the glucose metabolism of which is usually only slightly enhanced. Fluoride (18F) accumulates into the cortical bone, rapidly and intensely in reaction to a bony metastasis. In 2008, it has been granted a marketing authorisation in France, including imaging bone metastasis of prostate cancer. We report original clinical cases to illustrate its diagnostic performance. Whole-body MRI is developing and can also detect bone metastases. Recently diffusion-weighted MRI (DWI) has been proposed to increase the detection rate of metastases of the axial skeleton, which are largely predominant in prostate cancer. Using either hybrid PET/CT or MRI requires mobilising equipments, which are less available and more expensive than the gamma-cameras for classical bone scintigraphy, in the aim to achieve superior diagnostic performance. A clinical study protocol (STIC) has just been accepted for public funding. It aims to assess the impact on patient management of the discovery of the first macroscopic bony metastasis and the efficacy of diagnostic strategies including those innovations, individually and in association. In case of prostate cancer with a high risk of metastasis, but without any proven bone metastasis and no typical pattern on bone scintigraphy, fluoride (18F) PET/CT will be performed as well as whole-body MRI. Histopathology and/or data of a 6-month follow-up will be the standard of truth to evaluate the adequacy of impact on patient management and the benefit / cost ratio of those examinations. With this prospective national study, we hope to demonstrate in the real world a clinical role for this radiopharmaceutical, which was proposed several decades ago, but benefits from a renewed interest thanks to the development of PET/CT imaging. 相似文献