共查询到20条相似文献,搜索用时 31 毫秒
1.
《International journal of radiation applications and instrumentation. Part B, Nuclear medicine and biology》1988,15(2):123-126
Tumor accumulation of S-adenosyl-l-[methyl-11C]methionine ([11C]SAM) was investigated in mice bearing mammary carcinoma (FM3A) and in rats bearing ascitic hepatoma (AH109A). After injection of [11C]SAM the blood clearance of 11C radioactivity was rapid. The 11C level was relatively high in both tumors. The uptake ratios of tumor to organ increased with time in several organs, especially in brain and muscle. In FM3A tumor tissue the 11C was incorporated with time into the acid-precipitable fraction and 38% of the 11C was detected in this fraction at 60 min after injection. This fraction reflects the amount of 11C-methyl group transferred into macromolecules in tumor tissue. In AH109A-bearing rats the metabolisms of [11C]SAM and l-[methyl-11C]methionine ([11C]Met), in vivo precursor of SAM, were compared. Tumor uptake of [11C]SAM was about two thirds of that of [11C]Met at 20 min after injection. At this time, for the [11C]SAM 27 and 8% of the 11C in the AH109A tissue were detected in the acid-precipitable and the lipid fractions, respectively. The corresponding figures for [11C]Met were 61% and 2%. In the liver considerable amounts of 11C were observed in the lipid fraction for both tracers.These results show that [11C]SAM has potential as a tracer for tumor localization with positron emission tomography (PET) and suggest that in tumor studies combining [11C]Met and PET, it should be taken into account that the 11C-labeled methyl group of [11C]Met is not only incorporated into protein but also other macromolecules and lipids via [11C]SAM. 相似文献
2.
《Bioorganic & medicinal chemistry letters》2020,30(6):126998
[Thiocarbonyl-11C]disulfiram ([11C]DSF) was synthesized via iodine oxidation of [11C]diethylcarbamodithioic acid ([11C]DETC), which was prepared from [11C]carbon disulfide and diethylamine. The decay-corrected isolated radiochemical yield (RCY) of [11C]DSF was greatly affected by the addition of unlabeled carbon disulfide. In the presence of carbon disulfide, the RCY was increased up to 22% with low molar activity (Am, 0.27 GBq/μmol). On the other hand, [11C]DSF was obtained in 0.4% RCY with a high Am value (95 GBq/μmol) in the absence of carbon disulfide. The radiochemical purity of [11C]DSF was always >98%. The first PET study on [11C]DSF was performed in mice. A high uptake of radioactivity was observed in the liver, kidneys, and gallbladder. The uptake level and distribution pattern in mice were not significantly affected by the Am value of the [11C]DSF sample used. In vivo metabolite analysis showed the rapid decomposition of [11C]DSF in mouse plasma. 相似文献
3.
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
4.
《International journal of radiation applications and instrumentation. Part B, Nuclear medicine and biology》1991,18(3):281-288
Buprenorphine and diprenorphine were radiolabeled with 11C and their distributions in the baboon brain were studied using positron emission tomography (PET). Specific binding was demonstrated in the striatum (but not in the cerebellum) by pretreating the baboon with (−)naloxone. The absolute striatal uptakes and time courses were similar for these two radioligands but the ratio of radioactivity in the striatum to cerebellum in the baboon was higher for [11C]diprenorphine than for [11C]buprenorphine. Analysis of baboon plasma indicated that both [11C]diprenorphine and [11CJbuprenorphine are rapidly metabolized. Analysis of radioactivity in mouse brain indicated that these two radioligands are stable to metabolic transformation. At 30 min after injection, 86–90% of extracted radioactivity was due to unchanged 11C-labeled radioligands. These results suggest that both [11C]diprenorphine and [11C]buprenorphine may be useful radioligands for studying opioid receptors in humans, although [11C]diprenorphine may be a better radioligand than [11C]buprenorphine for this purpose because of its more rapid clearance from the cerebellum. 相似文献
5.
Min Wang Mingzhang Gao Qi-Huang Zheng 《Bioorganic & medicinal chemistry letters》2013,23(19):5259-5263
N-Desmethyl-loperamide and loperamide were synthesized from α,α-diphenyl-γ-butyrolactone and 4-(4-chlorophenyl)-4-hydroxypiperidine in five and four steps with 8% and 16% overall yield, respectively. The amide precursor was synthesized from 4-bromo-2,2-diphenylbutyronitrile and 4-(4-chlorophenyl)-4-hydroxypiperidine in 2 steps with 21–57% overall yield. [11C]N-Desmethyl-loperamide and [11C]loperamide were prepared from their corresponding amide precursor and N-desmethyl-loperamide with [11C]CH3OTf through N-[11C]methylation and isolated by HPLC combined with solid-phase extraction (SPE) in 20–30% and 10–15% radiochemical yields, respectively, based on [11C]CO2 and decay corrected to end of bombardment (EOB), with 370–740 GBq/μmol specific activity at EOB. 相似文献
6.
《International journal of radiation applications and instrumentation. Part B, Nuclear medicine and biology》1987,14(6):587-592
[11C]Cyanoimipramine has been prepared by methylation of the desmethyl cyanoimipramine with [11C]methyl iodide. The chemically and radiochemically pure labelled product was obtained with a high specific activity (> 300 mCi/μmol). When 11C (or 3H)-cyanoimipramine was intravenously administered in mice, high accumulations were shown in brain and lung. Thirty minutes after injection of the tracer, differences were found in the radioactivity between the cerebral cortex and the cerebellum. The regional distribution of radioactivity in the rat brain 30 min after i.v. injection of [11C]cyanoimipramine was also examined, and the radioactivity was high in receptor rich areas (striatum, cerebral cortex etc.) but low in receptor poor area (cerebellum). The in vivo stability of [3H]cyanoimipramine was quite stable in the mouse brain for at least 30 min. Thirty minutes after injection, the radioactivity in the cerebral cortex of the carrier-added state was reduced as compared with the carrier-free state. Taken together, the in vivo specific binding of [3H]cyanoimipramine in the cerebral cortex was estimated at about 40–50% of the total radioactivity. Furthermore, the distribution of [3H]cyanoimipramine in the mice forced to swim was examined. Significant changes in the distribution of [3H]cyanoimipramine were observed in the cerebral cortex. 相似文献
7.
《International journal of radiation applications and instrumentation. Part B, Nuclear medicine and biology》1988,15(4):365-371
As a tracer for in vivo studies on benzodiazepine receptors, 7-chloro-1,3-dihydro-5-(2-fluorophenyl)-1-[11C]methyl-2H-1, 4-benzodiazepin-2-one, [11C]fludiazepam, was synthesized by the methylation of norderivative with [11C]CH3I, and purified by high-performance liquid chromatography. Within 60 min [11C]fludiazepam was obtained for injection in high radiochemical yields and in high radiochemical purity with a specific activity of up to 230mCi/μmol.After i.v. injection of [11C]fludiazepam in rats the radioactivity was rapidly incorporated into many tissues and the blood clearance of the radioactivity was very rapid. The brain uptake was high and decreased gradually. The adrenal uptake was the highest and decreased with high loading doses. The effect of the loading dose on the uptake was also found in the heart and lungs. By autoradiography using [11C]fludiazepam, a higher accumulation was visualized in the cortex and thalamus than in other regions. 相似文献
8.
《Bioorganic & medicinal chemistry letters》2014,24(15):3622-3625
Retinoids are a class of chemical compounds which include both natural dietary vitamin A (retinol) metabolites and active synthetic analogs. Both experimental and clinical studies have revealed that retinoids regulate a wide variety of essential biological processes. In this study, we synthesized 11C-labeled all-trans-retinoic acid (ATRA), the most potent biologically active metabolite of retinol and used in the treatment of acute promyelocytic leukemia. The synthesis of 11C-labeled ATRA was accomplished by a combination of rapid Pd(0)-mediated C-[11C]methylation of the corresponding pinacol borate precursor prepared by 8 steps and hydrolysis. [11C]ATRA will prove useful as a PET imaging agent, particularly for elucidating the improved therapeutic activity of ATRA (natural retinoid) for acute promyelocytic leukemia by comparing with the corresponding PET probe [11C]Tamibarotene (artificial retinoid). 相似文献
9.
Min Wang Karmen K. Yoder Mingzhang Gao Bruce H. Mock Xiao-Ming Xu Andrew J. Saykin Gary D. Hutchins Qi-Huang Zheng 《Bioorganic & medicinal chemistry letters》2009,19(19):5636-5639
Fully automated synthesis and initial PET evaluation of a TSPO radioligand, [11C]PBR28 (N-(2-[11C]methoxybenzyl)-N-(4-phenoxypyridin-3-yl)acetamide), are reported. These results facilitate the potential preclinical and clinical PET studies of [11C]PBR28 in animals and humans. 相似文献
10.
Koichi Kato Ming-Rong Zhang Katsuyuki Minegishi Kazutoshi Suzuki 《Bioorganic & medicinal chemistry letters》2009,19(13):3439-3441
The nitroaldol reaction of nitro[11C]methane and formaldehyde using EtOH and EtONa efficiently provided 2-nitro[11C]ethanol in 3 min. The nitro group reduction in the presence of NiCl2 and NaBH4 in MeOH followed by purification using semi-preparative HPLC using 10% EtOH aqueous solution as an eluent proved to be a practical and accessible method for the synthesis of 2-amino[2-11C]ethanol. 相似文献
11.
Gao M Lola CM Wang M Miller KD Sledge GW Zheng QH 《Bioorganic & medicinal chemistry letters》2011,21(11):3222-3226
Vandetanib (ZD6474) and its chlorine analogue chloro-Vandetanib are potent and selective vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors with low nanomolar IC50 values. [11C]Vandetanib and [11C]chloro-Vandetanib, new potential PET agents for imaging of VEGFR in cancer, were first designed, synthesized and labeled at nitrogen and oxygen positions from their corresponding N- and O-des-methylated precursors, in 40-50% decay corrected radiochemical yield and 370-555 GBq/μmol specific activity at end of bombardment (EOB). 相似文献
12.
Jaya Prabhakaran Kiran Kumar Solingapuram Sai Anirudh Sattiraju Akiva Mintz J. John Mann J.S. Dileep Kumar 《Bioorganic & medicinal chemistry letters》2019,29(6):778-781
Dysfunction of GSK3 is implicated in the etiology of many brain, inflammatory, cardiac diseases, and cancer. PET imaging would enable in vivo detection and quantification of GSK3 and can impact the choice of therapy, allow non-invasive monitoring of disease progression and treatment effects. In this report, the synthesis and evaluation of a high affinity GSK3 ligand, [11C]2-(cyclopropanecarboxamido)-N-(4-methoxypyridin-3-yl)isonicotinamide, ([11C]CMP, (3), (IC50?=?3.4?nM, LogP?=?1.1) is described. [11C]CMP was synthesized in 25?±?5% yield by radiomethylating the corresponding phenolate using [11C]CH3I. The radioligand exhibited modest uptake in U251 human glioblastoma cell lines with ~50% specific binding. MicroPET studies in rats indicated negligible blood–brain barrier (BBB) penetration of [11C]CMP, despite its high affinity and suitable logP value for BBB penetration. However, administration of cyclosporine prior to [11C]CMP injection showed significant improvement in brain radioactivity uptake and the tracer binding. This finding indicates that [11C]CMP might be a P-gp efflux substrate and therefore has some limitations for routine in vivo PET evaluations in brain. 相似文献
13.
Hervé Boutin Christian Prenant Renaud Maroy James Galea Andrew D. Greenhalgh Alison Smigova Christopher Cawthorne Peter Julyan Shane M. Wilkinson Samuel D. Banister Gavin Brown Karl Herholz Michael Kassiou Nancy J. Rothwell 《PloS one》2013,8(2)
Purpose
Neuroinflammation is involved in several brain disorders and can be monitored through expression of the translocator protein 18 kDa (TSPO) on activated microglia. In recent years, several new PET radioligands for TSPO have been evaluated in disease models. [18F]DPA-714 is a TSPO radiotracer with great promise; however results vary between different experimental models of neuroinflammation. To further examine the potential of [18F]DPA-714, it was compared directly to [11C]PK11195 in experimental cerebral ischaemia in rats.Methods
Under anaesthesia, the middle cerebral artery of adult rats was occluded for 60 min using the filament model. Rats were allowed recovery for 5 to 7 days before one hour dynamic PET scans with [11C]PK11195 and/or [18F]DPA-714 under anaesthesia.Results
Uptake of [11C]PK11195 vs [18F]DPA-714 in the ischemic lesion was similar (core/contralateral ratio: 2.84±0.67 vs 2.28±0.34 respectively), but severity of the brain ischemia and hence ligand uptake in the lesion appeared to vary greatly between animals scanned with [11C]PK11195 or with [18F]DPA-714. To solve this issue of inter-individual variability, we performed a direct comparison of [11C]PK11195 and [18F]DPA-714 by scanning the same animals sequentially with both tracers within 24 h. In this direct comparison, the core/contralateral ratio (3.35±1.21 vs 4.66±2.50 for [11C]PK11195 vs [18F]DPA-714 respectively) showed a significantly better signal-to-noise ratio (1.6 (1.3–1.9, 95%CI) fold by linear regression) for [18F]DPA-714.Conclusions
In a clinically relevant model of neuroinflammation, uptake for both radiotracers appeared to be similar at first, but a high variability was observed in our model. Therefore, to truly compare tracers in such models, we performed scans with both tracers in the same animals. By doing so, our result demonstrated that [18F]DPA-714 displayed a higher signal-to-noise ratio than [11C]PK11195. Our results suggest that, with the longer half-life of [18F] which facilitates distribution of the tracer across PET centre, [18F]DPA-714 is a good alternative for TSPO imaging. 相似文献14.
Synthesis of (R,S)-[4-11C]baclofen via Michael addition of nitromethane labeled with short-lived 11C
Koichi Kato Ming-Rong Zhang Kazutoshi Suzuki 《Bioorganic & medicinal chemistry letters》2009,19(21):6222-6224
The synthesis of (R,S)-[4-11C]baclofen, the first 11C-labeled GABAB agonist, was demonstrated via Michael addition of nitro[11C]methane as a key step. A tetrabutylammonium fluoride promoted Michael addition of nitro[11C]methane to methyl p-chlorocinnamate, followed by the nitro-group reduction in the presence of NiCl2 and NaBH4 in aqueous MeOH and alkaline hydrolysis yielded (R,S)-[4-11C]baclofen in 36.4 ± 1.8% radiochemical conversion in three steps within 20 min. 相似文献
15.
Here we present a protocol for labeling aliphatic carboxylic acids with the positron-emitting radionuclide 11C (t(1/2) = 20.4 min) at the carboxyl position using [11C]carbon monoxide via photoinitiated free radical-mediated carbonylation. A solution of an alkyl iodide in a homogenous binary organic solvent-water mixture is introduced into a high-pressure photochemical reactor containing [11C]carbon monoxide. Then the reactor contents are pressurized to 40 MPa and irradiated with ultraviolet light for 6 min. The labeled product is purified using HPLC. All manipulations with radioactivity including the labeling synthesis are carried out on an automated Synthia system. In a typical case, 3.19 GBq of purified [1-(11)C]1,10-decanedicarboxylic acid (with a specific radioactivity of 188 GBq/micromol) can be obtained within 35 min after the end of a 10-microAh bombardment. Compared to previous labeling methods, this protocol is compatible with a wider range of functional groups, utilizes less-sensitive precursors, and is less subject to isotopic dilution. 相似文献
16.
《International journal of radiation applications and instrumentation. Part B, Nuclear medicine and biology》1992,19(1):27-32
The l-[methyl-11C]methionine ([11C]Met) uptake by rat AH109A tumor was decreased irradiation-dose dependently from the control to 5, 10 and 20 Gy. After 10 Gy irradiation, the [11C]Met uptake decreased earlier than the tumor volume reduction, and later, it significantly increased earlier than the recurrent growth. Double tracer autoradiography with [14C]Met and 4-[18F]fluoroantipyrine showed a decrease in the [14C]Met tumor uptake without change of blood flow after irradiation. The [11C]Met uptake representing amino acid metabolism is a sensitive indicator for monitoring radiotherapeutic effect on tumor. 相似文献
17.
Sylvie De Bruyne Leonie wyffels Lieselotte Moerman Johan Sambre Nicola A. Colabufo Francesco Berardi Roberto Perrone Filip De Vos 《Bioorganic & medicinal chemistry》2010,18(17):6489-6495
P-glycoprotein (P-gp) is an ATP-dependent efflux pump protecting the body against xenobiotics. The in vitro characterized modulator 6,7-dimethoxy-2-(6-methoxy-naphthalen-2-ylmethyl)-1,2,3,4-tetrahydroisoquinoline (MC80) of the P-gp pump was labelled with 11C and evaluated in vivo for its potential to image P-gp function and expression. Radiochemical pure (>98%) [11C]MC80 was obtained within 25 min starting from [11C]methyl iodide with radiochemical yield of 26%. Biodistribution studies in FVB mice demonstrated a high baseline brain uptake (7.66 ± 1.38%ID/g at 1 min pi). Cerebral uptake was increased in mdr1a knock-out mice as well as after CsA pretreatment. Pre-administration of an excess of non-radioactive MC80 caused a reduced uptake in several target organs including brain, pancreas and intestines. The results indicate that [11C]MC80 kinetics are modulated by P-gp. Reversed phase-HPLC analysis of brain revealed an excellent metabolic profile (>90% intact [11C]MC80). 相似文献
18.
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
19.
Kiran Kumar Solingapuram Sai Jaya Prabhakaran Anirudh Sattiraju J. John Mann Akiva Mintz J.S. Dileep Kumar 《Bioorganic & medicinal chemistry letters》2017,27(13):2895-2897
Radiosynthesis and evaluation of [11C]GSK1838705A in mice using microPET and determination of specificity in human GBM UG87MR cells are described herein. The radioligand was synthesized by reacting desmethyl-GSK1838705A with [11C]CH3I using GE FX2MeI module in ~5% yield (EOS), >95% radiochemical purity and a specific activity of 2.5 ± 0.5 Ci/μmol. MicroPET imaging in mice indicated that [11C]GSK1838705A penetrated blood brain barrier (BBB) and showed retention of radiotracer in brain. The radioligand exhibited high uptake in U87MG cells with >70% specific binding to IGF1R. Our experiments suggest that [11C]GSK-1838705A can be a potential PET radiotracer for the in vivo quantification of IGF1R expression in GBM and other brain tumors. 相似文献
20.
Jun Kosaka Hidehiko Takahashi Hiroshi Ito Akihiro Takano Yota Fujimura Ryohei Matsumoto Shoko Nozaki Fumihiko Yasuno Yoshiro Okubo Toshifumi Kishimoto Tetsuya Suhara 《Life sciences》2010,86(21-22):814-818
AimsAbnormality of cognitive function in schizophrenia has been suggested to be related to dopamine D1 receptor. However, the results of previous positron emission tomography (PET) studies of dopamine D1 receptor in schizophrenia were not consistent.Main methodsIn this study, six patients with schizophrenia in severe residual phase with chronic antipsychotic treatment and twelve healthy age-matched controls participated. Two different radioligands, [11C]NNC112 and [11C]SCH23390, for dopamine D1 receptor were used on the same subjects. Binding of the ligands was measured by PET, and statistical analysis was performed using one-way analysis of covariate (ANCOVA) with age as covariate.Key findingsGood correlations between binding potential values (BPND) and age were observed in all regions of interest (ROIs) with both ligands. ANCOVA with age as covariate of BPND values of all ROIs revealed that the patient group showed significantly lower BPND value compared with the control group in both ligands.SignificanceIn patients with chronic schizophrenia in severe residual phase with chronic antipsychotic treatment, the binding potential values of both ligands were significantly lower in the striatum and cortical regions than those of healthy controls. 相似文献