Browsing by Author "Ng, Yen"

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    Equivalence of arterial and venous blood for [11C]CO2-metabolite analysis following intravenous administration of 1-[11C]acetate and 1-[11C]palmitate
    (Elsevier, 2013-04) Ng, Yen; Moberly, Steven P.; Mather, Kieren J.; Brown-Proctor, Clive; Hutchins, Gary D.; Green, Mark A.; Department of Cellular & Integrative Physiology, IU School of Medicine
    PURPOSE: Sampling of arterial blood for metabolite correction is often required to define a true radiotracer input function in quantitative modeling of PET data. However, arterial puncture for blood sampling is often undesirable. To establish whether venous blood could substitute for arterial blood in metabolite analysis for quantitative PET studies with 1-[(11)C]acetate and 1-[(11)C]palmitate, we compared the results of [(11)C]CO2-metabolite analyses performed on simultaneously collected arterial and venous blood samples. METHODS: Paired arterial and venous blood samples were drawn from anesthetized pigs at 1, 3, 6, 8, 10, 15, 20, 25 and 30min after i.v. administration of 1-[(11)C]acetate and 1-[(11)C]palmitate. Blood radioactivity present as [(11)C]CO2 was determined employing a validated 10-min gas-purge method. Briefly, total blood (11)C radioactivity was counted in base-treated [(11)C]-blood samples, and non-[(11)C]CO2 radioactivity was counted after the [(11)C]-blood was acidified using 6N HCl and bubbled with air for 10min to quantitatively remove [(11)C]CO2. RESULTS: An excellent correlation was found between concurrent arterial and venous [(11)C]CO2 levels. For the [(11)C]acetate study, the regression equation derived to estimate the venous [(11)C]CO2 from the arterial values was: y=0.994x+0.004 (r(2)=0.97), and for the [(11)C]palmitate: y=0.964x-0.001 (r(2)=0.9). Over the 1-30min period, the fraction of total blood (11)C present as [(11)C]CO2 rose from 4% to 64% for acetate, and 0% to 24% for palmitate. The rate of [(11)C]CO2 appearance in venous blood appears similar for the pig model and humans following i.v. [(11)C]-acetate administration. CONCLUSION: Venous blood [(11)C]CO2 values appear suitable as substitutes for arterial blood samples in [(11)C]CO2 metabolite analysis after administration of [(11)C]acetate or [(11)C]palmitate ADVANCES IN KNOWLEDGE AND IMPLICATIONS FOR PATIENT CARE: Quantitative PET studies employing 1-[(11)C]acetate and 1-[(11)C]palmitate can employ venous blood samples for metabolite correction of an image-derived tracer arterial input function, thereby avoiding the risks of direct arterial blood sampling.
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    Impaired Cardiometabolic Responses to Glucagon-Like Peptide 1 in Obesity and Type 2 Diabetes Mellitus
    (Springer, 2013) Moberly, Steven P.; Mather, Kieren J.; Berwick, Zachary C.; Owen, Meredith K.; Goodwill, Adam G.; Casalini, Eli D.; Hutchins, Gary D.; Green, Mark A.; Ng, Yen; Considine, Robert V.; Perry, Kevin M.; Chisholm, Robin L.; Tune, Johnathan D.; Cellular and Integrative Physiology, School of Medicine
    Glucagon-like peptide 1 (GLP-1) has insulin-like effects on myocardial glucose uptake which may contribute to its beneficial effects in the setting of myocardial ischemia. Whether these effects are different in the setting of obesity or type 2 diabetes (T2DM) requires investigation. We examined the cardiometabolic actions of GLP-1 (7-36) in lean and obese/T2DM humans, and in lean and obese Ossabaw swine. GLP-1 significantly augmented myocardial glucose uptake under resting conditions in lean humans, but this effect was impaired in T2DM. This observation was confirmed and extended in swine, where GLP-1 effects to augment myocardial glucose uptake during exercise were seen in lean but not in obese swine. GLP-1 did not increase myocardial oxygen consumption or blood flow in humans or in swine. Impaired myocardial responsiveness to GLP-1 in obesity was not associated with any apparent alterations in myocardial or coronary GLP1-R expression. No evidence for GLP-1-mediated activation of cAMP/PKA or AMPK signaling in lean or obese hearts was observed. GLP-1 treatment augmented p38-MAPK activity in lean, but not obese cardiac tissue. Taken together, these data provide novel evidence indicating that the cardiometabolic effects of GLP-1 are attenuated in obesity and T2DM, via mechanisms that may involve impaired p38-MAPK signaling.
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    Performance of a 62Zn/62Cu microgenerator in kit-based synthesis and delivery of [62Cu]Cu–ETS for PET perfusion imaging
    (Elsevier B.V., 2014-09) Ng, Yen; Lacy, Jeffrey L.; Fletcher, James W.; Green, Mark A.; Department of Radiology and Imaging Sciences, IU School of Medicine
    The performance of a commercially produced 62Zn/62Cu microgenerator system, and an associated kit-based radiopharmaceutical synthesis method, was evaluated for clinical site production of [62Cu]Cu-ETS (ethylglyoxal bis(thiosemicarbazonato)copper(II)), an investigational agent for PET perfusion imaging. Using 37 generators, containing 1.84 ± 0.23 GBq 62Zn at 9:00 AM on the day of clinical use, a total of 45 patient doses of [62Cu]Cu-ETS (672 ± 172 MBq) were delivered without difficulty. 62Cu elution yields were high (approximately 90%), accompanied by extremely low 62Zn breakthrough (<0.001%). Radiopharmaceutical preparation, from the start-of-elution to time-of-injection, consumed less than five minutes. The 62Zn/62Cu microgenerator was a dependable source of short-lived positron-emitting 62Cu, and the kit-based synthesis proved to be rapid, robust, and highly reliable for “on-demand” delivery of [62Cu]Cu-ETS for PET perfusion imaging.
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    Whole-body PET/CT evaluation of tumor perfusion using generator-based 62Cu-ethylglyoxal bis(thiosemicarbazonato)copper(II): validation by direct comparison to 15O-water in metastatic renal cell carcinoma
    (Society of Nuclear Medicine and Molecular Imaging (SNMMI), 2015) Fletcher, James W.; Logan, Theodore F.; Eitel, Jacob A.; Mathias, Carla J.; Ng, Yen; Lacy, Jeffrey L.; Hutchins, Gary D.; Green, Mark A.; Radiology and Imaging Sciences, School of Medicine
    This study was undertaken to demonstrate the feasibility of whole-body (62)Cu-ethylglyoxal bis(thiosemicarbazonato)copper(II) ((62)Cu-ETS) PET/CT tumor perfusion imaging in patients with metastatic renal carcinoma and to validate (62)Cu-ETS as a quantitative marker of tumor perfusion by direct comparison with (15)O-water perfusion imaging. Methods: PET/CT imaging of 10 subjects with stage IV renal cell cancer was performed after intravenous administration of (15)O-water (10-min dynamic list-mode study) with the heart and at least 1 tumor in the PET field of view, followed 10 min later by intravenous (62)Cu-ETS (6-min list-mode study). Whole-body (62)Cu imaging was then performed from 6 to 20 min at 2-3 min/bed position. Blood flow (K1) was quantified with both agents for normal and malignant tissues in the 21.7-cm dynamic field of view. The required arterial input functions were derived from the left atrium and, in the case of (62)Cu-ETS, corrected for partial decomposition of the agent by blood with data from an in vitro analysis using a sample of each patient's blood. This imaging protocol was repeated at an interval of 3-4 wk after initiation of a standard clinical treatment course of the antiangiogenic agent sunitinib. Results: All subjects received the scheduled (62)Cu-ETS doses for the dynamic and subsequent whole-body PET/CT scans, but technical issues resulted in no baseline (15)O-water data for 2 subjects. Direct comparisons of the perfusion estimates for normal tissues and tumor metastases were made in 18 paired baseline and treatment studies (10 subjects; 8 baseline studies, 10 repeated studies during treatment). There was an excellent correlation between the blood flow estimates made with (62)Cu-ETS and (15)O-water for normal tissues (muscle, thyroid, myocardium) and malignant lesions (pulmonary nodules, bone lesions); the regression line was y = 0.85x + 0.15, R(2) = 0.83, for the 88 regions analyzed. Conclusion: (62)Cu-ETS provided high-quality whole-body PET/CT images, and (62)Cu-ETS measures of blood flow were highly and linearly correlated with (15)O-water-derived K1 values (mL(-1) ⋅ min(-1) ⋅ g). This tracer is suitable for use as a PET tracer of tumor perfusion in patients with metastatic renal cell carcinoma.