Amelia Moore - Academia.edu (original) (raw)

Papers by Amelia Moore

Seminars in Nuclear Medicine, 2009

Quantitative bone scan imaging has a useful role in research for examining the pathophysiology of... more Quantitative bone scan imaging has a useful role in research for examining the pathophysiology of metabolic bone diseases and the response of patients to treatment. The advantage of nuclear medicine imaging as a way of measuring the rate of bone remodeling is that either the whole skeleton or discrete regions of interest (ROIs) may be studied depending on whether there is diffuse or localized disease. This article reviews methods of quantifying (99m)Tc-methylene diphosphonate ((99m)Tc-MDP) kinetics based on a standard bone scan examination by measuring the plasma clearance of tracer to the whole skeleton and/or selected ROIs drawn on the bone scan image. Although the measurement of bone plasma clearance requires blood sampling to find the input curve for free (eg, nonprotein bound) (99m)Tc-MDP, we argue that plasma clearance studies give a more physiological approach in a better accord with the underlying changes in bone turnover than conventional measurements of whole-body retention or bone uptake. We describe 3 methods of measuring whole-skeleton (99m)Tc-MDP plasma clearance (K(bone)): (1) the area under the curve (AUC) method based on taking 6 blood samples at 5, 15, 60, 120, 180, and 240 minutes and measuring the plasma concentration of free (99m)Tc-MDP by ultrafiltration using a 30-kDa filter. The AUC method requires a simultaneous measurement of glomerular filtration rate using (51)Cr-EDTA as a cotracer; (2) the modified Brenner method, which measures K(bone) by drawing a soft-tissue ROI over the adductor muscles and plotting the soft tissue counts at 1, 2, 3, and 4 hours against the AUC values at the corresponding time points; (3) the Patlak method based on combining gamma camera measurements of whole-body retention with plasma data and measuring K(bone) from the slope of the Patlak plot fitted to the 2, 3, and 4 hours data points. Unlike the first 2 methods, the Patlak plot can also be used to measure regional values of K(bone) for any chosen ROI. Initial studies have shown good agreement between the 3 methods of measuring K(bone), and highly significant correlations between the change in K(bone) values during treatment and the corresponding changes in serum and urinary measurements of biochemical markers of bone formation and bone resorption.

Eur J Nucl Med Mol Imaging, 2003

It is widely believed that measurement of the area under the plasma clearance curve (AUC) followi... more It is widely believed that measurement of the area under the plasma clearance curve (AUC) following a single intravenous injection of chromium-51 labelled ethylene diamine tetra-acetic acid ( 51 Cr-EDTA) is a gold standard method for determining glomerular filtration rate (GFR). However, there are reports that 51 Cr-EDTA may have a significant extrarenal clearance. The aim of this study was to identify the non-renal component of 51 Cr-EDTA plasma clearance contributing to the AUC measurement of GFR. Seventy healthy postmenopausal women (mean age 60 years, range 45-79 years) were injected with 3 MBq 51 Cr-EDTA and 0.25 MBq iodine-125 labelled human serum albumin and 11 blood samples taken between 0 and 4 h through an indwelling venous cannula. For the first 21 subjects, two complete urine collections were made 0-2 h and 2-4 h after injection, and for the final 49 patients, four 1-h urine collections were made. The mean 51 Cr-EDTA total plasma clearance was 84 ml/min (range 50-132 ml/min). The mean ratio (SEM) of urine to total clearance determined from the cumulative 1-, 2-, 3-and 4-h data was 0.903 (0.018), 0.891 (0.013), 0.898 (0.011) and 0.899 (0.010) respectively and remained constant despite the mean urine concentration decreasing from 122% to 15%/litre during this period. A least squares fit to data from the 238 individual urine collections was used to determine the fraction of the total plasma clearance attributable to renal clearance, α 0 , and the residual urine volume, ∆V. The results were α 0 =0.910 (95% CI: 0.889-0.932) and ∆V=14 ml (95% CI: -4 to +34 ml). The overestimation of the true renal clearance of 51 Cr-EDTA by the AUC method is believed to be due to the failure of the plasma clearance curve to reach the true terminal exponential by 2 h after injection as usually assumed. As a result, conventional measurements of GFR using 51 Cr-EDTA overestimate the true renal clearance of tracer by approximately 10%.

Quantitative studies of bone using 99mTc-methylene diphospho- nate (MDP) reflect bone remodeling.... more Quantitative studies of bone using 99mTc-methylene diphospho- nate (MDP) reflect bone remodeling. The simplest method of evaluating 99mTc-MDP kinetics involves taking multiple blood samples and measuring total clearance (Ktotal) from the area un- der the plasma curve (AUC) and deriving bone clearance (Kbone) by subtracting glomerular filtration rate (GFR) from Ktotal. How- ever, the accuracy of the AUC method is

pared with the GFR method for the 5-, 10-, and 30-kDa filters were 0.894 0.010, 0.943 0.009, and ... more pared with the GFR method for the 5-, 10-, and 30-kDa filters were 0.894 0.010, 0.943 0.009, and 0.987 0.010. In study 2, the mean percentages (SD) of free 99mTc-MDP at 15 min and 4 h were 75.3% 8.0% and 48.8% 9.5%, with a precision error of 2.3%. The percentages of free MDP at 150 min and 4 h were

18F-fluoride positron emission tomography (18F-PET) studies to measure bone plasma clearance prov... more 18F-fluoride positron emission tomography (18F-PET) studies to measure bone plasma clearance provide a unique way of investigating regional bone formation that gives insight into the changes that occur during treatment at specific regional sites of interest that is not possible to obtain with biochemical markers of bone turnover. Quantitative 18F-PET studies are often performed using a protocol that involves a 60-minute dynamic scan. However, with a single injection of 18F-fluoride the region of interest (ROI) is restricted to the 15 cm axial field of view of the PET scanner so, for example, the lumbar spine or hip may be studied, but not both sites in the same examination. We present whole body 18F-PET studies of the skeleton using a new method [1] that enables estimation of regional 18F-fluoride bone plasma clearance from a series of short (5-minute) scans acquired at multiple sites of the skeleton following a single injection of tracer.

Nuclear medicine communications, 2007

The measurement of protein binding is essential for accurate quantitative studies of skeletal kin... more The measurement of protein binding is essential for accurate quantitative studies of skeletal kinetics using Tc-methylene diphosphonate (Tc-MDP). In this study, the dependence of Tc-MDP protein binding on total plasma clearance (Ktotal) and serum albumin concentration was investigated using data from two groups of patients. The first group (study 1) consisted of 71 patients referred for a Tc-MDP bone scan examination. The second group (study 2) consisted of 100 subjects referred for a determination of glomerular filtration rate (GFR) and injected with 3 MBq Tc-MDP and 3 MBq Cr-EDTA. Free Tc-MDP was measured using ultrafiltration and the percentage of free Tc-MDP analysed for the effect of Ktotal and serum albumin concentration using multivariate regression analysis. When the percentage of free Tc-MDP was analysed for the effect of Ktotal and serum albumin, highly significant relationships were found at the 2, 3 and 4 h time points. Subjects with higher values of Ktotal or serum albu...

Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 2006

Quantitative studies of bone using (99m)Tc-methylene diphosphonate (MDP) reflect bone remodeling.... more Quantitative studies of bone using (99m)Tc-methylene diphosphonate (MDP) reflect bone remodeling. The simplest method of evaluating (99m)Tc-MDP kinetics involves taking multiple blood samples and measuring total clearance (K(total)) from the area under the plasma curve (AUC) and deriving bone clearance (K(bone)) by subtracting glomerular filtration rate (GFR) from K(total). However, the accuracy of the AUC method is uncertain because of assumptions that the terminal exponential is reached by 2 h and that the rate constant k(4), representing the backflow of tracer from bone to plasma, is negligibly small. The aim of this study was to validate the accuracy of the AUC method by comparing K(bone) values obtained by that method with those obtained by gamma-camera imaging. Seventy-one patients were injected with 600 MBq of (99m)Tc-MDP. For the first 22 patients, whole-body images were acquired at 15 min and at 1, 2, 3, and 4 h after injection, whereas the remaining 49 were imaged at 15 mi...

Nuclear Medicine Communications, 2011

Introduction The use of image-derived arterial input functions (IDAIF) for the dynamic quantifica... more Introduction The use of image-derived arterial input functions (IDAIF) for the dynamic quantification of bone metabolism using 18 F-fluoride positron emission tomography 18 F-PET is an attractive alternative to direct arterial blood sampling.

Current Osteoporosis Reports, 2014

The functional imaging technique of dynamic fluorine-18 labeled sodium fluoride positron emission... more The functional imaging technique of dynamic fluorine-18 labeled sodium fluoride positron emission tomography ((18)F-NaF PET) allows the quantitative assessment of regional bone formation by measuring the plasma clearance of fluoride to bone at any site in the skeleton. (18)F-NaF PET provides a novel and noninvasive method of studying site-specific bone formation at the hip and spine, as well as areas of pure cortical or trabecular bone. The technique complements conventional measurements of bone turnover using biochemical markers and bone biopsy as a tool to investigate new treatments for osteoporosis, and holds promise of a future role as an early biomarker of treatment efficacy in clinical trials. This article reviews methods of acquiring and analyzing (18)F-NaF PET scan data, and outlines a simplified approach that uses 5-minute static PET scan images combined with venous blood samples to estimate (18)F-NaF plasma clearance at multiple sites in the skeleton with a single injection of tracer.

Nuclear Medicine Communications, 2012

Purpose We describe a semipopulation input function for evaluating bone plasma clearance from sta... more Purpose We describe a semipopulation input function for evaluating bone plasma clearance from static and dynamic 18 F-fluoride PET scans.

Radionuclide and Hybrid Bone Imaging, 2012

Seminars in Nuclear Medicine, 2009

Quantitative bone scan imaging has a useful role in research for examining the pathophysiology of... more Quantitative bone scan imaging has a useful role in research for examining the pathophysiology of metabolic bone diseases and the response of patients to treatment. The advantage of nuclear medicine imaging as a way of measuring the rate of bone remodeling is that either the whole skeleton or discrete regions of interest (ROIs) may be studied depending on whether there is diffuse or localized disease. This article reviews methods of quantifying (99m)Tc-methylene diphosphonate ((99m)Tc-MDP) kinetics based on a standard bone scan examination by measuring the plasma clearance of tracer to the whole skeleton and/or selected ROIs drawn on the bone scan image. Although the measurement of bone plasma clearance requires blood sampling to find the input curve for free (eg, nonprotein bound) (99m)Tc-MDP, we argue that plasma clearance studies give a more physiological approach in a better accord with the underlying changes in bone turnover than conventional measurements of whole-body retention or bone uptake. We describe 3 methods of measuring whole-skeleton (99m)Tc-MDP plasma clearance (K(bone)): (1) the area under the curve (AUC) method based on taking 6 blood samples at 5, 15, 60, 120, 180, and 240 minutes and measuring the plasma concentration of free (99m)Tc-MDP by ultrafiltration using a 30-kDa filter. The AUC method requires a simultaneous measurement of glomerular filtration rate using (51)Cr-EDTA as a cotracer; (2) the modified Brenner method, which measures K(bone) by drawing a soft-tissue ROI over the adductor muscles and plotting the soft tissue counts at 1, 2, 3, and 4 hours against the AUC values at the corresponding time points; (3) the Patlak method based on combining gamma camera measurements of whole-body retention with plasma data and measuring K(bone) from the slope of the Patlak plot fitted to the 2, 3, and 4 hours data points. Unlike the first 2 methods, the Patlak plot can also be used to measure regional values of K(bone) for any chosen ROI. Initial studies have shown good agreement between the 3 methods of measuring K(bone), and highly significant correlations between the change in K(bone) values during treatment and the corresponding changes in serum and urinary measurements of biochemical markers of bone formation and bone resorption.

Nuclear Medicine Communications, 2012

Aim The aim of this study was to evaluate the relationship between different quantification metho... more Aim The aim of this study was to evaluate the relationship between different quantification methods used for the measurement of bone plasma clearance (K i ) using 18 F-PET at the hip and lumbar spine.

Nuclear Medicine Communications, 2006

Nuclear Medicine Communications, 2002

Nuclear Medicine Communications, 2004

Seminars in Nuclear Medicine, 2009

Quantitative bone scan imaging has a useful role in research for examining the pathophysiology of... more Quantitative bone scan imaging has a useful role in research for examining the pathophysiology of metabolic bone diseases and the response of patients to treatment. The advantage of nuclear medicine imaging as a way of measuring the rate of bone remodeling is that either the whole skeleton or discrete regions of interest (ROIs) may be studied depending on whether there is diffuse or localized disease. This article reviews methods of quantifying (99m)Tc-methylene diphosphonate ((99m)Tc-MDP) kinetics based on a standard bone scan examination by measuring the plasma clearance of tracer to the whole skeleton and/or selected ROIs drawn on the bone scan image. Although the measurement of bone plasma clearance requires blood sampling to find the input curve for free (eg, nonprotein bound) (99m)Tc-MDP, we argue that plasma clearance studies give a more physiological approach in a better accord with the underlying changes in bone turnover than conventional measurements of whole-body retention or bone uptake. We describe 3 methods of measuring whole-skeleton (99m)Tc-MDP plasma clearance (K(bone)): (1) the area under the curve (AUC) method based on taking 6 blood samples at 5, 15, 60, 120, 180, and 240 minutes and measuring the plasma concentration of free (99m)Tc-MDP by ultrafiltration using a 30-kDa filter. The AUC method requires a simultaneous measurement of glomerular filtration rate using (51)Cr-EDTA as a cotracer; (2) the modified Brenner method, which measures K(bone) by drawing a soft-tissue ROI over the adductor muscles and plotting the soft tissue counts at 1, 2, 3, and 4 hours against the AUC values at the corresponding time points; (3) the Patlak method based on combining gamma camera measurements of whole-body retention with plasma data and measuring K(bone) from the slope of the Patlak plot fitted to the 2, 3, and 4 hours data points. Unlike the first 2 methods, the Patlak plot can also be used to measure regional values of K(bone) for any chosen ROI. Initial studies have shown good agreement between the 3 methods of measuring K(bone), and highly significant correlations between the change in K(bone) values during treatment and the corresponding changes in serum and urinary measurements of biochemical markers of bone formation and bone resorption.

Eur J Nucl Med Mol Imaging, 2003

It is widely believed that measurement of the area under the plasma clearance curve (AUC) followi... more It is widely believed that measurement of the area under the plasma clearance curve (AUC) following a single intravenous injection of chromium-51 labelled ethylene diamine tetra-acetic acid ( 51 Cr-EDTA) is a gold standard method for determining glomerular filtration rate (GFR). However, there are reports that 51 Cr-EDTA may have a significant extrarenal clearance. The aim of this study was to identify the non-renal component of 51 Cr-EDTA plasma clearance contributing to the AUC measurement of GFR. Seventy healthy postmenopausal women (mean age 60 years, range 45-79 years) were injected with 3 MBq 51 Cr-EDTA and 0.25 MBq iodine-125 labelled human serum albumin and 11 blood samples taken between 0 and 4 h through an indwelling venous cannula. For the first 21 subjects, two complete urine collections were made 0-2 h and 2-4 h after injection, and for the final 49 patients, four 1-h urine collections were made. The mean 51 Cr-EDTA total plasma clearance was 84 ml/min (range 50-132 ml/min). The mean ratio (SEM) of urine to total clearance determined from the cumulative 1-, 2-, 3-and 4-h data was 0.903 (0.018), 0.891 (0.013), 0.898 (0.011) and 0.899 (0.010) respectively and remained constant despite the mean urine concentration decreasing from 122% to 15%/litre during this period. A least squares fit to data from the 238 individual urine collections was used to determine the fraction of the total plasma clearance attributable to renal clearance, α 0 , and the residual urine volume, ∆V. The results were α 0 =0.910 (95% CI: 0.889-0.932) and ∆V=14 ml (95% CI: -4 to +34 ml). The overestimation of the true renal clearance of 51 Cr-EDTA by the AUC method is believed to be due to the failure of the plasma clearance curve to reach the true terminal exponential by 2 h after injection as usually assumed. As a result, conventional measurements of GFR using 51 Cr-EDTA overestimate the true renal clearance of tracer by approximately 10%.

Quantitative studies of bone using 99mTc-methylene diphospho- nate (MDP) reflect bone remodeling.... more Quantitative studies of bone using 99mTc-methylene diphospho- nate (MDP) reflect bone remodeling. The simplest method of evaluating 99mTc-MDP kinetics involves taking multiple blood samples and measuring total clearance (Ktotal) from the area un- der the plasma curve (AUC) and deriving bone clearance (Kbone) by subtracting glomerular filtration rate (GFR) from Ktotal. How- ever, the accuracy of the AUC method is

pared with the GFR method for the 5-, 10-, and 30-kDa filters were 0.894 0.010, 0.943 0.009, and ... more pared with the GFR method for the 5-, 10-, and 30-kDa filters were 0.894 0.010, 0.943 0.009, and 0.987 0.010. In study 2, the mean percentages (SD) of free 99mTc-MDP at 15 min and 4 h were 75.3% 8.0% and 48.8% 9.5%, with a precision error of 2.3%. The percentages of free MDP at 150 min and 4 h were

18F-fluoride positron emission tomography (18F-PET) studies to measure bone plasma clearance prov... more 18F-fluoride positron emission tomography (18F-PET) studies to measure bone plasma clearance provide a unique way of investigating regional bone formation that gives insight into the changes that occur during treatment at specific regional sites of interest that is not possible to obtain with biochemical markers of bone turnover. Quantitative 18F-PET studies are often performed using a protocol that involves a 60-minute dynamic scan. However, with a single injection of 18F-fluoride the region of interest (ROI) is restricted to the 15 cm axial field of view of the PET scanner so, for example, the lumbar spine or hip may be studied, but not both sites in the same examination. We present whole body 18F-PET studies of the skeleton using a new method [1] that enables estimation of regional 18F-fluoride bone plasma clearance from a series of short (5-minute) scans acquired at multiple sites of the skeleton following a single injection of tracer.

Nuclear medicine communications, 2007

The measurement of protein binding is essential for accurate quantitative studies of skeletal kin... more The measurement of protein binding is essential for accurate quantitative studies of skeletal kinetics using Tc-methylene diphosphonate (Tc-MDP). In this study, the dependence of Tc-MDP protein binding on total plasma clearance (Ktotal) and serum albumin concentration was investigated using data from two groups of patients. The first group (study 1) consisted of 71 patients referred for a Tc-MDP bone scan examination. The second group (study 2) consisted of 100 subjects referred for a determination of glomerular filtration rate (GFR) and injected with 3 MBq Tc-MDP and 3 MBq Cr-EDTA. Free Tc-MDP was measured using ultrafiltration and the percentage of free Tc-MDP analysed for the effect of Ktotal and serum albumin concentration using multivariate regression analysis. When the percentage of free Tc-MDP was analysed for the effect of Ktotal and serum albumin, highly significant relationships were found at the 2, 3 and 4 h time points. Subjects with higher values of Ktotal or serum albu...

Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 2006

Quantitative studies of bone using (99m)Tc-methylene diphosphonate (MDP) reflect bone remodeling.... more Quantitative studies of bone using (99m)Tc-methylene diphosphonate (MDP) reflect bone remodeling. The simplest method of evaluating (99m)Tc-MDP kinetics involves taking multiple blood samples and measuring total clearance (K(total)) from the area under the plasma curve (AUC) and deriving bone clearance (K(bone)) by subtracting glomerular filtration rate (GFR) from K(total). However, the accuracy of the AUC method is uncertain because of assumptions that the terminal exponential is reached by 2 h and that the rate constant k(4), representing the backflow of tracer from bone to plasma, is negligibly small. The aim of this study was to validate the accuracy of the AUC method by comparing K(bone) values obtained by that method with those obtained by gamma-camera imaging. Seventy-one patients were injected with 600 MBq of (99m)Tc-MDP. For the first 22 patients, whole-body images were acquired at 15 min and at 1, 2, 3, and 4 h after injection, whereas the remaining 49 were imaged at 15 mi...

Nuclear Medicine Communications, 2011

Introduction The use of image-derived arterial input functions (IDAIF) for the dynamic quantifica... more Introduction The use of image-derived arterial input functions (IDAIF) for the dynamic quantification of bone metabolism using 18 F-fluoride positron emission tomography 18 F-PET is an attractive alternative to direct arterial blood sampling.

Current Osteoporosis Reports, 2014

The functional imaging technique of dynamic fluorine-18 labeled sodium fluoride positron emission... more The functional imaging technique of dynamic fluorine-18 labeled sodium fluoride positron emission tomography ((18)F-NaF PET) allows the quantitative assessment of regional bone formation by measuring the plasma clearance of fluoride to bone at any site in the skeleton. (18)F-NaF PET provides a novel and noninvasive method of studying site-specific bone formation at the hip and spine, as well as areas of pure cortical or trabecular bone. The technique complements conventional measurements of bone turnover using biochemical markers and bone biopsy as a tool to investigate new treatments for osteoporosis, and holds promise of a future role as an early biomarker of treatment efficacy in clinical trials. This article reviews methods of acquiring and analyzing (18)F-NaF PET scan data, and outlines a simplified approach that uses 5-minute static PET scan images combined with venous blood samples to estimate (18)F-NaF plasma clearance at multiple sites in the skeleton with a single injection of tracer.

Nuclear Medicine Communications, 2012

Purpose We describe a semipopulation input function for evaluating bone plasma clearance from sta... more Purpose We describe a semipopulation input function for evaluating bone plasma clearance from static and dynamic 18 F-fluoride PET scans.

Radionuclide and Hybrid Bone Imaging, 2012

Seminars in Nuclear Medicine, 2009

Quantitative bone scan imaging has a useful role in research for examining the pathophysiology of... more Quantitative bone scan imaging has a useful role in research for examining the pathophysiology of metabolic bone diseases and the response of patients to treatment. The advantage of nuclear medicine imaging as a way of measuring the rate of bone remodeling is that either the whole skeleton or discrete regions of interest (ROIs) may be studied depending on whether there is diffuse or localized disease. This article reviews methods of quantifying (99m)Tc-methylene diphosphonate ((99m)Tc-MDP) kinetics based on a standard bone scan examination by measuring the plasma clearance of tracer to the whole skeleton and/or selected ROIs drawn on the bone scan image. Although the measurement of bone plasma clearance requires blood sampling to find the input curve for free (eg, nonprotein bound) (99m)Tc-MDP, we argue that plasma clearance studies give a more physiological approach in a better accord with the underlying changes in bone turnover than conventional measurements of whole-body retention or bone uptake. We describe 3 methods of measuring whole-skeleton (99m)Tc-MDP plasma clearance (K(bone)): (1) the area under the curve (AUC) method based on taking 6 blood samples at 5, 15, 60, 120, 180, and 240 minutes and measuring the plasma concentration of free (99m)Tc-MDP by ultrafiltration using a 30-kDa filter. The AUC method requires a simultaneous measurement of glomerular filtration rate using (51)Cr-EDTA as a cotracer; (2) the modified Brenner method, which measures K(bone) by drawing a soft-tissue ROI over the adductor muscles and plotting the soft tissue counts at 1, 2, 3, and 4 hours against the AUC values at the corresponding time points; (3) the Patlak method based on combining gamma camera measurements of whole-body retention with plasma data and measuring K(bone) from the slope of the Patlak plot fitted to the 2, 3, and 4 hours data points. Unlike the first 2 methods, the Patlak plot can also be used to measure regional values of K(bone) for any chosen ROI. Initial studies have shown good agreement between the 3 methods of measuring K(bone), and highly significant correlations between the change in K(bone) values during treatment and the corresponding changes in serum and urinary measurements of biochemical markers of bone formation and bone resorption.

Nuclear Medicine Communications, 2012

Aim The aim of this study was to evaluate the relationship between different quantification metho... more Aim The aim of this study was to evaluate the relationship between different quantification methods used for the measurement of bone plasma clearance (K i ) using 18 F-PET at the hip and lumbar spine.

Nuclear Medicine Communications, 2006

Nuclear Medicine Communications, 2002

Nuclear Medicine Communications, 2004