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51.
52.
Minn H Grönroos TJ Komar G Eskola O Lehtiö K Tuomela J Seppänen M Solin O 《Current pharmaceutical design》2008,14(28):2932-2942
Non-invasive detection of tumor hypoxia using radiolabeled 2-nitroimidazoles has been a major effort during the last two decades. Recent years have witnessed the introduction of several new compounds which are chemically related to [(18)F]fluoromisonidazole (FMISO) but show slight but distinct differences in biodistribution and metabolic clearance. Although [(18)F]FMISO has shown clinical potential it suffers from suboptimal oxygen dependent tissue contrast and newer agents seek to improve this essential feature. The limited data on other interesting tracers keeps the investigators busy at demonstrating the potential advantages over [(18)F]FMISO while efforts should start to concentrate on proving the clinical significance of such techniques in the form of outcome data from image-guided therapy modification. We review here our experiences with two hypoxia-avid agents [(18)F]fluoroerythronitromidazole (FETNIM) and [(18)F] 2-(2-nitro-1-H-imidazol-1-yl)-N-(2,2,3,3,3-pentafluoropropyl)-acetamide (EF5) and focus on the similarities and differences of these two tracers in comparison to other radiolabeled 2-nitroimidazoles. It is recognized that only [(18)F]FMISO has thus far shown clinical utility and newer tracers need to be tested against this circumstance. 相似文献
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54.
Blood metabolism of [methyl-
11C]choline; implications for in vivo imaging with positron emission tomography 总被引:1,自引:1,他引:0
Anne Roivainen Sarita Forsback Tove Grönroos Pertti Lehikoinen Meri Kähkönen Eija Sutinen Heikki Minn 《European journal of nuclear medicine and molecular imaging》2000,27(1):25-32
[methyl-11C]Choline (11C-choline) is a radioligand potentially useful for oncological positron emission tomography (PET). As a first step towards
the development of a kinetic model for quantification of 11C-choline uptake, blood metabolism of 11C-choline during PET imaging was studied in humans. High-performance liquid chromatography (HPLC) and thin-layer chromatography
(TLC) were used for the analysis of 11C-choline and its radioactive metabolites. Prior to human PET imaging we studied ex vivo the biodistribution and metabolism
of intravenously administered 11C-choline in rats. Our results revealed that the radioactivity accumulated particularly in kidney, lung, adrenal gland and
liver. Chromatographic analysis showed that the level of unmetabolized 11C-choline in rat plasma decreased from 42%±20% (mean±SD) at 5 min to 21%±10% at 15 min after injection. In accordance with
these findings, in humans the unmetabolized 11C-choline represents 62%±19% of the total radioactivity in arterial plasma at 5 min after injection and 27%±12% at 15 min.
In human venous plasma the corresponding values were 85%±12% and 48%±12% at 5 and 10 min, respectively. The major metabolite
observed in both human and rat plasma was identified as 11C-betaine. In human arterial plasma this maximally represented 82%±9% of the total radioactivity at 25 min after radiotracer
injection. By 20 min after injection, the 11C-choline and 11C-betaine in human arterial plasma reached a plateau, and their fractional activities remained nearly constant thereafter.
Although most of the circulating 11C-choline in blood is transported to tissues, it does not disappear totally from blood within the first 40 min after tracer injection.
Received 7 July and in revised form 16 September 1999 相似文献
55.
Yu Kyung Kim Dohsik Minn Do Young Song Chae Hoon Lee Nam Hee Ryoo Chang-Ho Jeon Kyung Eun Song Jang Soo Suh Soon Hee Chang 《Journal of Korean medical science》2021,36(43)
BackgroundIn Korea, the first community outbreak of coronavirus disease 2019 (COVID-19) occurred in Daegu on February 18, 2020. This study was performed to investigate the prevalence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) antibodies in healthcare workers (HCWs) at 6 major hospitals in Daegu.MethodsBlood specimens of 2,935 HCWs at 6 major hospitals in Daegu from January 2021 to February 2021 were collected. Every specimen was tested for antibody against SARS-CoV-2 using both Elecsys Anti-SARS-CoV-2 electrochemiluminescence immunoassay (Roche Diagnostics, Rotkreuz, Switzerland) and R-FIND COVID-19 IgG/M/A enzyme-linked immunosorbent assay kit (SG medical Inc., Seoul, Korea) as screening tests. If 1 or more of these screening test results was positive, 2 additional antibody tests were performed using Abbott Anti-SARS-CoV-2 IgG assay (Abbott, Abbott Park, IL, USA) and cPass SARS-CoV-2 Neutralization Antibody Detection Kit (GenScript USA Inc., Piscataway, NJ, USA). If 2 or more of the total 4 test results were positive, it was determined as positive for the antibody against SARS-CoV-2.ResultsAccording to the criteria of SARS-CoV-2 antibody positivity determination, 12 subjects were determined as positive. The overall positive rate of the SARS-CoV-2 antibody was 0.41% (12/2,935). Of the 12 subjects determined as positive, 7 were diagnosed with COVID-19, and the remaining 5 were nondiagnosed cases of COVID-19.ConclusionIn early 2021, the overall seroprevalence of SARS-CoV-2 antibody among HCW located in Daegu was 0.41%, and 0.17% excluding COVID-19 confirmed subjects. These results were not particularly high compared with the general public and were much lower than HCWs in other countries. 相似文献
56.
57.
Seth A. Wander Dekuang Zhao Alexandra H. Besser Feng Hong Jianqin Wei Tan A. Ince Clara Milikowski Nanette H. Bishopric Andy J. Minn Chad J. Creighton Joyce M. Slingerland 《Breast cancer research and treatment》2013,138(2):369-381
Oncogenic PI3K/mTOR activation is frequently observed in human cancers and activates cell motility via p27 phosphorylations at T157 and T198. Here we explored the potential for a novel PI3K/mTOR inhibitor to inhibit tumor invasion and metastasis. An MDA-MB-231 breast cancer line variant, MDA-MB-231-1833, with high metastatic bone tropism, was treated with a novel catalytic PI3K/mTOR inhibitor, PF-04691502, at nM doses that did not impair proliferation. Effects on tumor cell motility, invasion, p27 phosphorylation, localization, and bone metastatic outgrowth were assayed. MDA-MB-231-1833 showed increased PI3K/mTOR activation, high levels of cytoplasmic p27pT157pT198 and increased cell motility and invasion in vitro versus parental. PF-04691502 treatment, at a dose that did not affect proliferation, reduced total and cytoplasmic p27, decreased p27pT157pT198 and restored cell motility and invasion to levels seen in MDA-MB-231. p27 knockdown in MDA-MB-231-1833 phenocopied PI3K/mTOR inhibition, whilst overexpression of the phosphomimetic mutant p27T157DT198D caused resistance to the anti-invasive effects of PF-04691502. Pre-treatment of MDA-MB-231-1833 with PF-04691502 significantly impaired metastatic tumor formation in vivo, despite lack of antiproliferative effects in culture and little effect on primary orthotopic tumor growth. A further link between cytoplasmic p27 and metastasis was provided by a study of primary human breast cancers which showed cytoplasmic p27 is associated with increased lymph nodal metastasis and reduced survival. Novel PI3K/mTOR inhibitors may oppose tumor metastasis independent of their growth inhibitory effects, providing a rationale for clinical investigation of PI3K/mTOR inhibitors in settings to prevent micrometastasis. In primary human breast cancers, cytoplasmic p27 is associated with worse outcomes and increased nodal metastasis, and may prove useful as a marker of both PI3K/mTOR activation and PI3K/mTOR inhibitor efficacy. 相似文献
58.
The regional and subcellular distributions of rat brain cytochrome P450 and cytochrome P450-dependent activities were examined. Cytochrome P450 was found to be mainly localized in mitochondria in all the six cerebral regions studied. The activities of the isoforms mostly implicated in drug metabolism, cytochromes P450 b and c, were measured by the dealkylation of two alkoxyresorufins, that are sensitive probe substrates for these isoforms. These activities have been measured in microsomal and mitochondrial fractions obtained from six different regions in male rat brains, as well as in microvessels. Resorufin derivatives dealkylation specific activities were higher in brain microsomal fractions than in hepatic ones in all the six regions examined when results were expressed per cytochrome P450 content. These brain microsomal specific activities were also higher than in mitochondrial fractions. Olfactory bulbs showed the highest cytochrome P450 content and activities in both microsomal and mitochondrial fractions. A sex-linked difference in cytochrome P450-dependent activities was also found. After an in vivo inducing pretreatment of rats, only 3-methylcholanthrene induced ethoxyresorufin O-deethylase activity, in the three preparations studied. These results provided (i) direct evidence that cytochromes P450 b and c isoforms are active in brain microsomal fractions, with regional and sex-linked differences, and (ii) the first demonstration of cytochrome P450-dependent activities in isolated rat brain microvessels. 相似文献
59.
60.
Tolvanen T Någren K Yu M Sutinen E Havu-Aurén K Jyrkkiö S Asola M Kotoneva E Nuutila P Minn H 《European journal of nuclear medicine and molecular imaging》2006,33(10):1178-1184
Purpose [N-methyl-11C]α-methylaminoisobutyric acid ([11C]MeAIB) is a promising positron emission tomography (PET) tracer for imaging hormonally regulated system A amino acid transport. Uptake of [11C]MeAIB is totally specific for amino acid transport since [11C]MeAIB is metabolically stable both extra- and intracellularly. The aim of this study was to measure cumulated radioactivity in different organs and estimate the absorbed radiation doses to humans with the Medical Internal Radiation Dosimetry (MIRD) method.Methods Radiation absorbed doses were calculated from PET images for 25 volunteers. Dynamic acquisition data were obtained for the thoracic, abdominal, femoral and head and neck regions. The median dose of intravenously injected [11C]MeAIB was 422±35 MBq, with a range of 295–493 MBq. After PET imaging the radioactivity in voided urine was measured. Experimental human data were used for residence time estimates. Radiation doses were calculated with commonly used software.Results The effective dose for a 70-kg adult was 0.004 mSv/MBq, corresponding to a 1.72 mSv effective dose from the PET study with injection of 430 MBq [11C]MeAIB. The highest absorbed doses were in the pancreas (0.018 mGy/MBq), kidneys (0.017 mGy/MBq), intestine (0.014 mGy/MBq), liver (0.008 mGy/MBq) and stomach (0.005 mGy/MBq). Only 0.57% of injected activity was excreted to urine within 1 h after injection.Conclusion Biodistribution of [11C]MeAIB in the abdominal region reflected the high activity of the transportation of amino acids via system A and these organs also had the highest radiation doses. An effective dose of 0.004 mSv/MBq is fully justified when [11C]MeAIB PET is performed to study system A activity in vivo. 相似文献