Measurements of Myocardial Fatty Acid Metabolism With PET and [F-18]FluorbetaOx in Humans With Heart Failure With and Without Diabetes: Comparison With [C-11]Palmitate

A single center, open-label baseline controlled imaging study to designed to assess whether Positron Emission Tomography (PET) measurements of myocardial Fatty Acid (FA) metabolism performed with [18F]FluorbetaOx correlates with measurements using [11C]palmitate. This study involves the investigational use of a PET radioactive tracer, fluorine-18 radiolabeled fatty acid analog, [18F]FluorbetaOx designed to measure beta oxidation of fatty acids in the myocardium. The investigators propose to evaluate the feasibility of the method in heart failure patients with dilated non-ischemic cardiomyopathy (DCM) with or without type-2 diabetes mellitus (T2DM) and obese subjects (Body Mass Index of ≥ 30kg/m2) with or without T2DM and normal healthy subjects to provide a wide range of perturbations in myocardial FA metabolism.
Specific objectives include:
To assess the diagnostic quality of [18F]FluorbetaOx PET images and kinetics at the proposed 10 millicurie (mCi) dose.
To quantitatively determine the relationship between PET measurements of myocardial FA metabolism obtained with [18F]FluorbetaOx and those using [11C]Palmitate.
To calculate human dosimetry based on the human biodistribution of [18F]FluorbetaOx.
Correlate measurements of myocardial FA metabolism with changes in left ventricular (LV)structure and function performed on a clinically indicated echocardiography at 6-9 months after imaging.

开始日期2012-09-13

申办/合作机构

Washington University School of Medicine

100 项与 [18F]FluorbetaOx 相关的临床结果

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100 项与 [18F]FluorbetaOx 相关的转化医学

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100 项与 [18F]FluorbetaOx 相关的专利（医药）

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项与 [18F]FluorbetaOx 相关的文献（医药）

1999-06-01·Journal of nuclear medicine : official publication, Society of Nuclear Medicine

Characterization of [18F]fluoroetanidazole, a new radiopharmaceutical for detecting tumor hypoxia.

Article

作者: Rasey, J S ; Chin, L K ; Hofstrand, P D ; Tewson, T J

Fluorinated derivatives of etanidazole are being explored as probes for tumor hypoxia. Our research group has synthesized [18F]fluoroetanidazole (FETA) and now reports the oxygen dependency of binding to cells in vitro, the biodistribution of the tracer in tumor-bearing mice and the analysis of metabolites in their plasma and urine.METHODSFour cultured rodent cell lines (V79, 36B10, EMT6 and RIF1) were incubated with [18F]FETA for various times under graded O2 concentrations. We also compared the biodistributions of [18F]FETA and [18F]fluoromisonidazole (FMISO) at 2 and 4 h postinjection in C3H mice bearing KHTn tumors (130-430 mg). Reverse-phase high-performance liquid chromatography was used to distinguish metabolites from parent drugs in urine and plasma of mice injected with [18F]FETA or [18F]FMISO.RESULTSIn cells labeled in vitro, O2 levels of 600-1300 ppm inhibited binding by 50% relative to uptake under anoxic conditions (<10 ppm). These inhibitory values are not statistically different from those reported for [18F]FMISO in the same cell lines (700-1500 ppm). In the biodistribution studies, uptake in heart, intestine, kidney and tumor was similar for both tracers 4 h after injection, whereas retention of [18F]FETA in liver and lung was significantly lower. Less uptake of [18F]FETA in liver suggests that this nitroimidazole is metabolized less than [18F]FMISO. The brain-to-blood ratios indicate that [18F]FETA readily crosses the blood-brain barrier. High-performance liquid chromatography of urine demonstrated that 10% of [18F]FETA-derived activity was in metabolites at 2 h postinjection, with 15% in metabolites by 4 h; comparable values for [18F]FMISO were 36% and 57%, respectively.CONCLUSIONWe conclude from these data that [18F]FETA holds promise as a new hypoxia tracer in patients, having oxygen dependency of binding similar to [18F]FMISO in vitro and displaying less retention in liver and fewer metabolites in vivo.

1999-01-01·Nuclear Medicine and Biology

Comparative breast tumor imaging and comparative in vitro metabolism of 16α-[18F]Fluoroestradiol-17β and 16β-[18f]fluoromoxestrol in isolated hepatocytes

Article

作者: Thomas A Bonasera ; Farrokh Dehdashti ; Michael J Welch ; Stephanie D Jonson ; John A Katzenellenbogen ; Michael E Cristel

16beta-[18F]Fluoromoxestrol ([18]betaFMOX) is an analog of 16alpha-[18F]fluoroestradiol-17beta ([18F]FES), a radiopharmaceutical known to be an effective positron emission tomography (PET) imaging agent for estrogen receptor-positive (ER+) human breast tumors. Based on comparisons of target tissue uptake efficiency and selectivity in a rat model, [18F]betaFMOX was predicted to be as effective an imaging agent as [18F]FES. However, in a preliminary PET imaging study with [18F]FMOX of 12 patients, 3 of whom had ER+ breast cancer, no tumor localization of [18F]betaFMOX was observed. In search for an explanation for the unsuccessful [18F]betaFMOX clinical trial, we have examined the rate of metabolism of [18F]FMOX and [18F]FES in isolated rat, baboon, and human hepatocytes. We have also studied the effect of the serum protein sex hormone-binding globulin (SHBG), which binds [18F]FES better than [18F]betaFMOX, on these rates of metabolism. Immature rat hepatocytes were found to metabolize [18F]FES 31 times faster than [18F]betaFMOX, whereas mature rat cells metabolized [18F]FES only 3 times faster, and baboon and human hepatocytes only 2 times faster than [18F]betaFMOX. In the presence of SHBG, the metabolic consumption rate for [18F]FES in mature rat hepatocytes decreased by 26%. Thus, the very favorable target tissue uptake characteristics of [18F]betaFMOX determined in the rat probably result from its comparative resistance to metabolism (vis-a-vis [18F]FES) in this species, an advantage that is strongly reflected in comparative metabolism rates in rat hepatocytes. In the baboon and human, [18F]FES is extensively protein bound and protected from metabolism, an effect that may be reflected to a degree as a decrease in the rate of metabolism of this compound in baboon and human hepatocytes relative to [18F]betaFMOX. Thus in primates, SHBG may potentiate the ER-mediated uptake of [18F]FES in ER+ tumors by selectively protecting this ligand from metabolism and ensuring its delivery to receptor-containing cells. In addition to current screening methods for 18F-estrogens that involve evaluating in vivo ER-mediated uptake in the immature female rat, studies comparing the metabolism of the new receptor ligands in isolated hepatocytes, especially those from primates or humans, may assist in predicting the potential of these ligands for human PET imaging.

100 项与 [18F]FluorbetaOx 相关的药物交易

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适应症	最高研发状态	国家/地区	公司	日期
扩张型心肌病	临床1期	美国	Washington University School of Medicine	2012-09-13
2型糖尿病	临床1期	美国	Washington University School of Medicine	2012-09-13
心脏衰竭	临床1期	美国	Washington University School of Medicine	2012-09-13
肥胖	临床1期	美国	Washington University School of Medicine	2012-09-13

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT01648296 (CTgov)	早期临床1期	2型糖尿病 \| 心脏衰竭 \| 肥胖	50	[18F]FluorbetaOx (Dosimetry Group)	夢構構顧選糧獵鏇選衊(遞夢製遞憲繭艱繭網願) = 鏇餘願壓積鹹夢繭網製憲顧餘觸願鏇壓夢繭網 (齋簾選觸襯襯窪鏇醖窪, 淵製膚鏇衊艱窪網窪憲 ~ 襯築膚齋艱遞觸糧積艱) 更多	-	2019-11-27
				[18F]FluorbetaOx (Kinetic Dynamic Group)	夢構構顧選糧獵鏇選衊(遞夢製遞憲繭艱繭網願) = 廠醖艱願蓋觸醖觸衊簾憲顧餘觸願鏇壓夢繭網 (齋簾選觸襯襯窪鏇醖窪, 鹹範壓襯壓鏇構夢製廠 ~ 鑰鏇窪衊壓齋遞顧餘製) 更多