共查询到20条相似文献,搜索用时 78 毫秒
1.
Zhengxing Zhang Joseph Lau Hsiou-Ting Kuo Chengcheng Zhang Nadine Colpo François Bénard Kuo-Shyan Lin 《Bioorganic & medicinal chemistry letters》2017,27(10):2094-2098
The potent and selective prostanoid EP4 receptor antagonist CJ-042794 was radiolabeled with 18F, and evaluated for imaging EP4 receptor expression in cancer with positron emission tomography (PET). The fluorination precursor, arylboronic acid pinacol ester 4, was prepared in 4 steps with 42% overall yield. 18F-CJ-042794 was synthesized via a copper-mediated 18F-fluorination reaction followed by base hydrolysis, and was obtained in 1.5 ± 1.1% (n = 2) decay-corrected radiochemical yield. PET/CT imaging and biodistribution studies in mice showed that 18F-CJ-042794 was excreted through both renal and hepatobiliary pathways with significant retention in blood. The EP4-receptor-expressing LNCaP prostate cancer xenografts were clearly visualized in PET images with 1.12 ± 0.08%ID/g (n = 5) uptake value and moderate tumour-to-muscle contrast ratio (2.73 ± 0.22) at 1 h post-injection. However, the tumour uptake was nonspecific as it could not be blocked by co-injection of cold standard, precluding the application of 18F-CJ-042794 for PET imaging of EP4 receptor expression in cancer. 相似文献
2.
Geng-Ying Li Daria D. Vaulina Jia-Je Li Olga S. Fedorova Hsin-Ell Wang Ren-Shyan Liu Raisa N. Krasikova Chuan-Lin Chen 《Bioorganic & medicinal chemistry letters》2017,27(15):3460-3463
Given the ever-present demand for improved PET radiotracer in oncology imaging, we have synthesized 2-(3,4-dimethoxyphenyl)-6-(2-[18F]fluoroethoxy)benzothiazole ([18F]FEDBT), a fluorine-18-containing fluoroethylated benzothiazole to explore its utility as a PET imaging tracer. [18F]FEDBT was prepared via kryptofix-mediated nucleophilic substitution of the tosyl group precursor. Fractionated ethanol-based solid-phase (SPE cartridge-based) purification afforded [18F]FEDBT in 60% radiochemical yield (EOB), with radiochemical purity in excess of 98% and the specific activity was 35 GBq/μmol. The radiotracer displayed clearly higher cellular uptake ratio in various breast cancer cell lines MCF7, MDA-MB-468 and MDA-MB-231. However, both biodistribution and microPET studies have showed an higher abdominal accumulation of [18F]FEDMBT and the tumor/muscle ratio of 1.8 was observed in the MDA-MB-231 xenograft tumors mice model. Further the lipophilic improvement is needed for the reducement of hepatobilliary accumulation and to promote the tumor uptake for PET imaging of breast cancer. 相似文献
3.
Bouvet V Wuest M Tam PH Wang M Wuest F 《Bioorganic & medicinal chemistry letters》2012,22(6):2291-2295
A new synthesis of O-(2-[18F]fluoroethyl)-l-tyrosine [18F]FET was developed using a NanoTek® microfluidic synthesis system (Advion BioSciences, Inc.). Optimal reaction conditions were studied through screening different reaction parameters like temperature, flow rate, reaction time, concentration of the labeling precursor, and the applied volume ratio between the labeling precursor and [18F]fluoride. [18F]FET was obtained after HPLC purification with 50% decay-corrected radiochemical yield starting from as little as 40 μg of labeling precursor. Small animal PET studies in EMT-6 tumor bearing mice showed radioactivity accumulation in the tumor (SUV60min 1.21 ± 0.2) resulting in an slightly increasing tumor-to-muscle ratio over time. 相似文献
4.
Tiantian Mou Huihui Jing Wenjiang Yang Wei Fang Cheng Peng Feng Guo Xianzhong Zhang Yan Pang Yunchuan Ma 《Bioorganic & medicinal chemistry》2010,18(3):1312-1320
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-[18F]fluroethoxy)ethoxy]benzyloxy]-4-chloro-2H-pyridazin-3-one ([18F]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-[19F]fluroethoxy)ethoxy]benzyloxy]-4-chloro-2H-pyridazin-3-one ([19F]FP2OP) were synthesized and characterized by IR, 1H NMR, 13C NMR and MS analysis. By substituting tosyl of precursor OTs-P2OP with 18F, the radiolabeled complex [18F]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 [18F]F? Kryptofix 2.2.2./K2CO3 solution, the total reaction time for [18F]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 [18F]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 [18F]FP2OP in blood and urine at 30 min. Ex vivo autoradiography demonstrates that [18F]FP2OP may have high affinity with MC-I and that can be blocked by [19F]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: [18F]FP2OP was synthesized with high radiochemical yield. The promising biological properties of [18F]FP2OP suggest high potential as MPI agent for positron emission tomography in the future. 相似文献
5.
《Médecine Nucléaire》2023,47(4):200-207
ObjectiveOur aim in this retrospective study was to compare the diagnostic accuracy of 68Ga-FAPI-04 PET/CT and 18F-FDG PET/CT in detecting bone metastases of various cancers and to evaluate the potential usefulness of 68Ga-FAPI-04 PET/CT in detecting metastatic bone disease.Material and methodOur retrospective study included 44 patients diagnosed with bone metastases due to various cancers between January 2021 and February 2022. All patients underwent 68Ga-FAPI-04 PET/CT and 18F-FDG PET/CT imaging within 14 days. In the semi-quantitative analysis of the skeletal system, all regions with higher uptake than background activity were considered pathological. SUVmax and Metastasis-to-background ratio (TBR) values were calculated from metastatic sites.ResultsA total of 827 bone metastases were detected in our study. The diagnostic accuracies of FAPI PET/CT and 18F-FDG PET/CT were 91.8% and 81.5%, respectively (P < 0.001). When all bone metastases were compared, the SUVmax of 68Ga-FAPI-04 PET/CT was statistically significantly higher than that of 18F-FDG PET/CT (median 6.15 vs. 5.2; P < 0.001). When FDG and FAPI SUVmax values were compared according to metastasis types, FAPI SUVmax and TBR values in osteolytic, medullary and mixed type bone metastases were found to be statistically significantly higher than FDG (P-values: < 0.001, < 0.001, < 0.001, respectively). There was no statistically significant difference between FDG and FAPI SUVmax values in osteoblastic bone metastases (P = 0.26).ConclusionIt has been shown that 68Ga-FAPI-04 PET/CT is superior to 18F-FDG PET/CT in detecting metastatic bone disease and may have more clinical impact on disease management. 相似文献
6.
Vattoly J. Majo Victoria Arango Norman R. Simpson Jaya Prabhakaran Suham A. Kassir Mark D. Underwood Mihran Bakalian Peter Canoll J. John Mann J.S. Dileep Kumar 《Bioorganic & medicinal chemistry letters》2013,23(14):4191-4194
Radiosynthesis and in vitro evaluation of [18F](S)-1-(4-((5-cyclopropyl-1H-pyrazol-3-yl)amino)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N-(6-fluoropyridin-3-yl)-2-methylpyrrolidine-2-carboxamide ([18F]BMS-754807 or [18F]1) a specific IGF-1R inhibitor was performed. [18F]1 demonstrated specific binding in vitro to human cancer tissues. Synthesis of reference standard 1 and corresponding bromo derivative (1a), the precursor for radiolabeling were achieved from 2,4-dichloropyrrolo[2,1-f][1,2,4]triazine (4) in three steps with 50% overall yield. The radioproduct was obtained in 8% yield by reacting 1a with [18F]TBAF in DMSO at 170 °C at high radiochemical purity and specific activity (1–2 Ci/μmol, N = 10). The proof of concept of IGF-IR imaging with [18F]1 was demonstrated by in vitro autoradiography studies using pathologically identified surgically removed grade IV glioblastoma, breast cancer and pancreatic tumor tissues. These studies indicate that [18F]1 can be a potential PET tracer for monitoring IGF-1R. 相似文献
7.
Xia Wang Yan Li Winnie Deuther-Conrad Fang Xie Xin Chen Meng-Chao Cui Xiao-Jun Zhang Jin-Ming Zhang Jörg Steinbach Peter Brust Bo-Li Liu Hong-Mei Jia 《Bioorganic & medicinal chemistry》2013,21(1):215-222
We report the synthesis and evaluation of a series of fluoro-oligo-ethoxylated 4-benzylpiperazine derivatives as potential σ1 receptor ligands. In vitro competition binding assays showed that 1-(1,3-benzodioxol-5-ylmethyl)-4-(4-(2-fluoroethoxy)benzyl)piperazine (6) exhibits low nanomolar affinity for σ1 receptors (Ki = 1.85 ± 1.59 nM) and high subtype selectivity (σ2 receptor: Ki = 291 ± 111 nM; Kiσ2/Kiσ1 = 157). [18F]6 was prepared in 30–50% isolated radiochemical yield, with radiochemical purity of >99% by HPLC analysis after purification, via nucleophilic 18F? substitution of the corresponding tosylate precursor. The log DpH 7.4 value of [18F]6 was found to be 2.57 ± 0.10, which is within the range expected to give high brain uptake. Biodistribution studies in mice demonstrated relatively high concentration of radiotracers in organs known to contain σ1 receptors, including the brain, lungs, kidneys, heart, and spleen. Administration of haloperidol 5 min prior to injection of [18F]6 significantly reduced the concentration of radiotracers in the above-mentioned organs. The accumulation of radiotracers in the bone was quite low suggesting that [18F]6 is relatively stable to in vivo defluorination. The ex vivo autoradiography in rat brain showed high accumulation of radiotracers in the brain areas known to possess high expression of σ1 receptors. These findings suggest that [18F]6 is a suitable radiotracer for imaging σ1 receptors with PET in vivo. 相似文献
8.
Tomoteru Yamasaki Masayuki Fujinaga Yoko Shimoda Wakana Mori Yiding Zhang Hidekatsu Wakizaka Masanao Ogawa Ming-Rong Zhang 《Bioorganic & medicinal chemistry letters》2017,27(17):4114-4117
Cannabinoid receptor type 1 (CB1) is mainly expressed in the brain, as well as being expressed in functional relevant concentrations in various peripheral tissues. 1-(4-Chlorophenyl)-3-(3-(6-(pyrrolidin-1-yl)pyridin-2-yl)phenyl)urea (PSNCBAM-1, 1) was developed as a potent allosteric antagonist for CB1 and its oral administration led to reductions in the appetite and body weight of rats. Several analogs of 1 (compounds 2 and 3) were recently identified through a series of structure-activity relationship studies. Herein, we report the synthesis of radiolabeled analogs of these compounds using [11C]COCl2 and an evaluation of their potential as PET ligands for CB1 imaging using in vitro and in vivo techniques. [11C]2 and [11C]3 were successfully synthesized in two steps using [11C]COCl2. The radiochemical yields of [11C]2 and [11C]3 were 17 ± 8% and 20 ± 9% (decay-corrected to the end of bombardment, based on [11C]CO2). The specific activities of [11C]2 and [11C]3 were 42 ± 36 and 37 ± 13 GBq/μmol, respectively. The results of an in vitro binding assay using brown adipose tissue (BAT) homogenate showed that the binding affinity of 2 for CB1 (KD = 15.3 µM) was much higher than that of 3 (KD = 26.0 µM). PET studies with [11C]2 showed a high uptake of radioactivity in BAT, which decreased in animals pretreated with AM281 (a selective antagonist for CB1). In conclusion, [11C]2 may be a useful PET ligand for imaging peripheral CB1 in BAT. 相似文献
9.
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
10.
S. Gonzalez Olivier Mundler Christophe Doddoli Fabrice Barlesi Thomas Tessonnier Bardia Farman Serge Cammilleri Laurent Boyer Eric Guedj Laurent Tessonnier 《Médecine Nucléaire》2018,42(4):206-213
Purpose
To evaluate diagnostic impact of routinely use of respiratory gated (RG) 18FDG PET/CT to distinguish benign and malignant lung nodules.Methods
We analyzed retrospectively data of 76 patients referred for metabolic characterization of lung nodules who underwent whole body 18FDG PET/CT scan followed by RG PET/CT (deep-inspiration breath-hold, DIBH). RG was prospectively planned without knowledge of WB PET/CT results. Independent reading of PET/CT scans with or without respiratory gating was separately conducted by two nuclear medicine physicians. Uptake of lung nodules was evaluated visually (positive if nodule's uptake superior to pulmonary background uptake), and quantitatively (SUVmax, SUVmean, metabolic volume, tumor to background ratio). Reference standard was obtained for all patients by histology (n = 37) or clinico-radiological follow-up (n = 39). Sub-groups were also evaluated (nodule < 15 mm, lower lobe nodules).Results
Nodules were classified positives without RG scans in 43/76 (59.7%) patients and with RG scans in 41/75 (54.6%) patients. Results were discordant for 5/75 (6.7%) patients. According to the reference standard, 35/39 cancers were correctly identified by PET/CT without RG, and 34/38 by RG PET/CT. Without RG PET, sensitivity, specificity and accuracy were 89.7%, 78.4% and 84.2% respectively. With RG PET, sensitivity, specificity and accuracy were 89.5%, 81.1% and 85.3% respectively, not statistically different. Concerning quantitative analysis, results were not statistically better with RG than without RG and were not better than visual analysis. Sub-groups analysis showed no added value of RG scans in specific groups (lower lobes and smaller nodules).Conclusion
Routinely use of RG did not help in the diagnosis of neoplastic lung nodules. Others evaluations are needed to assess the contribution of RG for others selective indications (therapeutic evaluation, radiotherapy planning, characterization of liver lesions). 相似文献11.
Shuting Zhang Xiao Wang Yong He Rui Ding Hang Liu Jingli Xu Man Feng Guixia Li Ming Wang Cheng Peng Chuanmin Qi 《Bioorganic & medicinal chemistry》2010,18(7):2394-2401
This article reported the synthesis and bioevaluation of two [18F] labeled benzimidazole derivatives, 4-(5-(2-[18F] fluoro-4-nitrobenzamido)-1-methyl-1H-benzimidazol-2-yl) butanoic acid ([18F] FNBMBBA, [18F]a1) and 3-(2-fluoroethyl)-7-methyl-2-propyl-3H-benzimidazole-5-carboxylic acid ([18F] FEMPBBA, [18F]b1) for PET tumor imaging. The preparation [18F] FEMPBBA was completed in 1 h with overall radiochemical yield of 50–60% (without decay corrected). Biodistribution assay in S180 tumor bearing mice of both compounds were carried out, and the results are both meaningful. [18F] FEMPBBA which can be taken as a revision of [18F] FNBMBBA got an excellent result, and has significant advantages in some aspects compared with L-[18F] FET and [18F]-FDG in the same animal model, especially in tumor/brain uptake ratio. The tumor/brain uptake ratio of [18F] FEMPBBA gets to 4.81, 7.15, and 9.8 at 30 min, 60 min and 120 min, and is much higher than that of L-[18F] FET (2.54, 2.92 and 2.95) and [18F]-FDG (0.61, 1.02, 1.33) at the same time point. The tumor/muscle and tumor/blood uptake ratio of [18F] FEMPBBA is also higher than that of L-[18F] FET at 30 min and 60 min. This result indicates compound [18F] FEMPBBA is a promising radiotracer for PET tumor imaging. 相似文献
12.
Weiping Yu Larry Williams Vernon M. Camp Jeffrey J. Olson Mark M. Goodman 《Bioorganic & medicinal chemistry letters》2010,20(7):2140-2143
A new [18F] labeled amino acid anti-1-amino-2-[18F]fluoro-cyclobutyl-1-carboxylic acid 9 (anti-2-[18F]FACBC) was synthesized in 30% decay-corrected yield with high radiochemical purity over 99%. The cyclic sulfamidate precursor was very stable and highly reactive towards nucleophilic radiofluorination. Cell uptake assays with rat 9L gliosarcoma cells showed that [18F]9 was transported into tumor cells via multiple amino acid transport systems, including L and A systems. Biodistribution study in rats with intracranial 9L gliosarcoma tumors demonstrated that [18F]9 had a rapid and prolonged accumulation in tumors with 26:1 tumor to brain ratio at 120 min post-injection. In this model, [18F]9 is a potential PET tracer for brain tumor imaging. 相似文献
13.
Wenjiang Yang Tiantian Mou Wenyan Guo Huihui Jing Cheng Peng Xianzhong Zhang Yunchuan Ma Boli Liu 《Bioorganic & medicinal chemistry letters》2010,20(16):4840-4844
Galactosylated chitosan (GC) was prepared by reacting lactobionic acid with water-soluble chitosan. GC was labeled with fluorine-18 by conjugation with N-succinimidyl-4-18F-fluorobenzoate ([18F]SFB) under a slightly basic condition. After rapid purification with HiTrap desalting column, [18F]FB-GC was obtained with high radiochemical purity (>97%) determined by radio-HPLC. The total reaction time for [18F]FB-GC was about 150 min. Typical decay-corrected radiochemical yield was about 4–8%. Ex vivo biodistribution in normal mice showed that [18F]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 [18F]FB-GC significantly declined in all selected time points. The better liver retention properties of [18F]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. 相似文献
14.
K. Serdons T. Verduyckt D. Vanderghinste J. Cleynhens P. Borghgraef P. Vermaelen C. Terwinghe F. Van Leuven K. Van Laere H. Kung G. Bormans A. Verbruggen 《Bioorganic & medicinal chemistry letters》2009,19(3):602-605
2-(4′-[18F]fluorophenyl)-1,3-benzothiazole was synthesized as a fluorine-18 labelled derivative of the Pittsburg Compound-B (PIB), which has known affinity for amyloid β and promising characteristics as tracer for in vivo visualisation of amyloid deposits in patients suffering from Alzheimer’s disease (AD). Both the nitro-precursor 2-(4′-nitrophenyl)-1,3-benzothiazole and the non-radioactive reference compound were synthesized using a 1-step synthesis pathway. Labelling was achieved by direct aromatic nucleophilic substitution of the nitro-precursor using [18F]fluoride by heating for 20 min at 150 °C and with a radiochemical yield of 38%. The reference compound showed high affinity for amyloid in an in vitro competition binding study using human AD brain homogenates (Ki = 9.0 nM) and fluorescence imaging of incubated transgenic APP mouse brain slices confirmed binding to amyloid plaques. A biodistribution study in normal mice showed a high brain uptake at 2 min pi (3.20% ID/g) followed by a fast washout (60 min pi: 0.21% ID/g). A dynamic μPET study was performed in a transgenic APP and normal WT mouse, but, similar to [11C]PIB, no difference was seen in tracer retention between both kind of mice. The new 18F-labelled 2-phenylbenzothiazole showed excellent preclinical characteristics comparable with those of the 11C-labelled PIB. 相似文献
15.
《Bioorganic & medicinal chemistry》2016,24(21):5326-5339
Positron emission tomography (PET) using fluorine-18 (18F)-labeled 2-nitroimidazole radiotracers has proven useful for assessment of tumor oxygenation. However, the passive diffusion-driven cellular uptake of currently available radiotracers results in slow kinetics and low tumor-to-background ratios. With the aim to develop a compound that is actively transported into cells, 1-(6′-deoxy-6′-[18F]fluoro-β-d-allofuranosyl)-2-nitroimidazole (β-[18F]1), a putative nucleoside transporter substrate, was synthetized by nucleophilic [18F]fluoride substitution of an acetyl protected labeling precursor with a tosylate leaving group (β-6) in a final radiochemical yield of 12 ± 8% (n = 10, based on [18F]fluoride starting activity) in a total synthesis time of 60 min with a specific activity at end of synthesis of 218 ± 58 GBq/μmol (n = 10). Both radiolabeling precursor β-6 and unlabeled reference compound β-1 were prepared in multistep syntheses starting from 1,2:5,6-di-O-isopropylidene-α-d-allofuranose. In vitro experiments demonstrated an interaction of β-1 with SLC29A1 and SLC28A1/2/3 nucleoside transporter as well as hypoxia specific retention of β-[18F]1 in tumor cell lines. In biodistribution studies in healthy mice β-[18F]1 showed homogenous tissue distribution and excellent metabolic stability, which was unaffected by tissue oxygenation. PET studies in tumor bearing mice showed tumor-to-muscle ratios of 2.13 ± 0.22 (n = 4) at 2 h after administration of β-[18F]1. In ex vivo autoradiography experiments β-[18F]1 distribution closely matched staining with the hypoxia marker pimonidazole. In conclusion, β-[18F]1 shows potential as PET hypoxia radiotracer which merits further investigation. 相似文献
16.
Federica Pisaneschi Quang-De Nguyen Elham Shamsaei Matthias Glaser Edward Robins Maciej Kaliszczak Graham Smith Alan C. Spivey Eric O. Aboagye 《Bioorganic & medicinal chemistry》2010,18(18):6634-6645
The epidermal growth factor receptor (EGFR/c-ErbB1/HER1) is overexpressed in many cancers including breast, ovarian, endometrial, and non-small cell lung cancer. An EGFR specific imaging agent could facilitate clinical evaluation of primary tumors and/or metastases. To achieve this goal we designed and synthesized a small array of fluorine containing compounds based on a 3-cyanoquinoline core. A lead compound, 16, incorporating 2′-fluoroethyl-1,2,3-triazole was selected for evaluation as a radioligand based on its high affinity for EGFR kinase (IC50 = 1.81 ± 0.18 nM), good cellular potency (IC50 = 21.97 ± 9.06 nM), low lipophilicity and good metabolic stability. ‘Click’ labeling afforded [18F]16 in 37.0 ± 3.6% decay corrected radiochemical yield based on azide [18F]14 and 7% end of synthesis (EOS) yield from aqueous fluoride. Compound [18F]16 was obtained with >99% radiochemical purity in a total synthesis time of 3 h. The compound showed good stability in vivo and a fourfold higher uptake in high EGFR expressing A431 tumor xenografts compared to low EGFR expressing HCT116 tumor xenografts. Furthermore, the radiotracer could be visualized in A431 tumor bearing mice by small animal PET imaging. Compound [18F]16 therefore constitutes a promising radiotracer for further evaluation for imaging of EGFR status. 相似文献
17.
J.R. García Garzón 《Médecine Nucléaire》2013,37(3):78-82
18F-sodium fluoride uptake mechanism is based on the fluoride ion exchange, with a hydroxyl group of the hydroxyapatite being at the surface of the bone crystals and thus forming fluorapatite, especially at sites with a high rate of bone remodeling. 18F-fluoride shows a lower protein binding and faster plasma clearance with respect to 99mTc-diphosphonates (twice increased bone uptake). The adult dose range is 185–370 MBq, whereas in children it is advisable to adjust dose (0.057 mCi/kg). The acquisition time of the 18F-fluoride PET study is similar to that of 18F-FDG one (60 ± 30 minutes). The CT is required for attenuation correction (low amperage 30 mAs) but also allows artifact reduction and quantification. 18F-fluoride PET shows high sensitivity for detection of bone metastases, affecting its specificity. However, CT addition may increase specificity, resulting in a high accuracy of 18F-fluoride PET/CT. Given its uptake mechanism, its sensitivity is higher for mixed and blastic metastases rather than for lytic ones. Multiple studies have shown that the sensitivity of the 18F-fluoride is higher than bone scan, including whole-body bone SPECT. However, 18F-fluoride PET/CT should find their real indications in the current algorithms of clinical practice. 相似文献
18.
Linhong He Da Li Chufeng Zhang Peng Bai Lijuan Chen 《Bioorganic & medicinal chemistry letters》2017,27(17):4171-4175
Described as a Btk inhibitor, ibrutinib also potently inhibits Bmx and EGFR, two good targets for lung cancer. Owing to its high CLogP (4.07) and low aqueous solubility (<0.01 mg/ml), resulting in unfavorable bioavailability, ibrutinib requires high dosages to achieve good clinical response in the treatment of non-small cell lung cancer (NSCLC). In our effort to improve the CLogP of ibrutinib by structural optimization led to the discovery of a potent anti-cancer agent B6, with beneficial physicochemical parameters (CLogP = 2.56, solubility in water ≈ 0.1 mg/ml) meeting the principles of oral drugs. B6 exhibited anti-proliferation activities against EGFR-expressing cells, especially the mutant ones, such as H1975 (L858R/T790M, IC50 = 0.92 ± 0.19 μM) and HCC827 (Del119 IC50 = 0.014 ± 0.01 μM). Moreover, B6 significantly slowed down H1975 tumor growth with anti-tumor rate of 73.9% (p < 0.01). Enzyme potencies assay demonstrated B6 moderately selectively inhibited Bmx (IC50 = 35.7 ± 0.1 nM) over other kinases. So, as a potent Bmx inhibitor, B6 has the potential to be an efficacious treatment for NSCLC with acquired drug resistance. 相似文献
19.
Alessandra Monaco Vincent Zoete Gian Carlo Alghisi Curzio Rüegg Olivier Michelin John Prior Leonardo Scapozza Yann Seimbille 《Bioorganic & medicinal chemistry letters》2013,23(22):6068-6072
The development of RGD-based antagonist of αvβ3 integrin receptor has enhanced the interest in PET probes to image this receptor for the early detection of cancer, to monitor the disease progression and the response to therapy. In this work, a novel prosthetic group (N-(4-fluorophenyl)pent-4-ynamide or FPPA) for the 18F-labeling of an αvβ3 selective RGD-peptide was successfully prepared. [18F]FPPA was obtained in three steps with a radiochemical yield of 44% (decay corrected). Conjugation to c(RGDfK(N3)) by the Cu(II) catalyzed Huisgen azido alkyne cycloaddition provided the [18F]FPPA-c(RGDfK) with a radiochemical yield of 29% (decay corrected), in an overall synthesis time of 140 min. 相似文献
20.
Kiran Kumar Solingapuram Sai Bhaskar C. Das Anirudh Sattiraju Frankis G. Almaguel Suzanne Craft Akiva Mintz 《Bioorganic & medicinal chemistry letters》2017,27(6):1425-1427
Retinoic acid receptor alpha (RAR-α) plays a significant role in a number of diseases, including neuroblastoma. Children diagnosed with high-risk neuroblastoma are treated 13-cis-retinoic acid, which reduces risk of cancer recurrence. Neuroblastoma cell death is mediated via RAR-α, and expression of RAR-α is upregulated after treatment. A molecular imaging probe that binds RAR-α will help clinicians to diagnose and stratify risk for patients with neuroblastoma, who could benefit from retinoid-based therapy. In this study, we report the radiolabeling, and initial in vivo evaluation of [18F]KBM-1, a novel RAR-α agonist. The radiochemical synthesis of [18F]KBM-1 was carried out through KHF2 assisted substitution of [18F]? from aryl-substituted pinacolatoesters-based retinoid precursor. In vitro cell uptake assay in human neuroblastoma cell line showed that the uptake of [18F]KBM-1 was significantly inhibited by all three blocking agents (KBM-1, ATRA, BD4) at all the selected incubation times. Standard biodistribution in mice bearing neuroblastoma tumors demonstrated increased tumor uptake from 5 min to 60 min post radiotracer injection and the uptake ratios for target to non-target (tumor: muscle) increased 2.2-fold to 3.7-fold from 30 min to 60 min post injection. Tumor uptake in subset of 30 min blocking group was 1.7-fold lower than unblocked. These results demonstrate the potential utility of [18F]KBM-1 as a RAR-α imaging agent. 相似文献