Quantitative evaluation of manganese-52m as a myocardial perfusion tracer in pigs using positron emission tomography

Buck, Alfred; Nguyen, Ngoc; Burger, Cyrill; Ziegler, Sibylle; Frey, L.; Weigand, Gabriele; Erhardt, W.; Senekowitsch–Schmidtke, Reingard; Pellikka, Raimo; Bläuenstein, Peter; Locher, J. T.; Schwaiger, Markus

doi:10.1007/bf01249625

Cited by 20 publications

(13 citation statements)

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“…19,26 And third, protein binding complicates the use of Mn 2þ for blood flow measurement. Buck et al 62 used the radiotracer, 52m Mn, for positron emission tomography (PET) measurement of myocardial blood flow from first pass profiles and found that qualitative but not quantitative assessment of blood flow could be obtained. A true 4-fold increase in blood flow was underestimated as a 2.6-fold increase.…”

Section: Intravenous Administration Of Mn 2þ Ionmentioning

confidence: 99%

“…Mn 2þ is highly diffusible and its tissue distribution is flow-limited. 62 However, the driving force for diffusive extravasation is the low and largely unknown unbound fraction of Mn 2þ , not the total concentration that may be measured in the blood over time by external imaging. Unchelated Mn 2þ is rapidly cleared from the circulation via the liver.…”

Section: Intravenous Administration Of Mn 2þ Ionmentioning

confidence: 99%

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Applications of manganese‐enhanced magnetic resonance imaging (MEMRI) to imaging of the heart

Wendland

2004

NMR in Biomedicine

101

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The use of manganese-based MRI contrast materials, either manganese salts or chelates, has spanned the entire timeframe of cardiac MRI. However interest in Mn compounds for cardiac MRI has been sporadic because of concerns over cardiotoxicity associated with significant concentration of free Mn 2þ and notable success of gadolinium chelates in cardiac application. Initial strategies to overcome cardiotoxicity included chelation of Mn 2þ to reduce the concentration of the free ion in vivo, and addition of Ca 2þ in combination with Mn 2þ to competitively reduce binding of Mn 2þ to Ca 2þ channels in the heart. Both approaches met with mixed success, but were subsequently discontinued in favor of gadolinium-based approaches. However Mn 2þ -based media potentially offer unique advantages for characterizing heart pathology over conventional Gd-based contrast media because Mn 2þ is taken up by heart cells and retained for hours. Cellular uptake occurs through calcium channels so contrast on delayed images may be interpreted according to regional or global functional status. Since Mn 2þ is retained in the heart, Mn-based media can be administered outside the magnet and the contrast pattern measured hours later to provide assessment of uptake. A key issue is whether sufficient accumulation of Mn 2þ in heart cells for imaging can occur without cardiotoxicity, and findings to date indicate this is possible. This review examines the current status of Mn 2þ -enhanced MRI of heart with particular focus on the hypothesis that Mn 2þ uptake can be interpreted in terms of heart function. Copyright # 2004 John Wiley & Sons, Ltd.KEYWORDS: magnetic resonance imaging; manganese; contrast media; myocardial ischemia; myocardial function; myocardial perfusion OVERVIEW Manganese (II) was the first MRI contrast agent. Lauterbur et al. 1 found that administration of inorganic salts of divalent Mn increased R 1 , particularly in liver, kidney, and heart. 2 In the heart increased R 1 of tissue was proportional to quantity of Mn 2þ accumulated within it, 1,2 and both quantity of Mn 2þ and R 1 enhancement were reduced in myocardium distal to an occluded artery. Mn 2þ was considered a promising contrast material for use in cardiac MRI because of its potent R 1 enhancement, its fairly rapid uptake by heart cells and its only moderate toxicity. Manganese is an essential trace mineral with a stable physiologic pool and a physiological system for handling it. Most notably, manganese is essential to aerobic organisms because Mn 2þ is required by mitochondrial superoxide dismutase (SOD). 3 The important issue was the moderate toxicity. In addition to manganese poisoning, which caused parkinsonism-like symptoms after chronic overexposure, Mn 2þ was known to block normal calcium fluxes in the heart, which caused a prominent cardiotoxicity. A dose of 0.1 mmol/kg administered by rapid intravenous injection kills rats, 2 stopping the heart within a few minutes. After a few early encouraging MRI studies with low doses of MnCl 2 , 2,4,5 Wolf and Ba...

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Section: Intravenous Administration Of Mn 2þ Ionmentioning

confidence: 99%

Section: Intravenous Administration Of Mn 2þ Ionmentioning

confidence: 99%

Applications of manganese‐enhanced magnetic resonance imaging (MEMRI) to imaging of the heart

Wendland

2004

NMR in Biomedicine

101

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“…The SUV is widely used in oncologic imaging and normalizes tissue uptake with weight of the patient and injected dose. Most of the earlier human and animal-model studies using SPECT or PET flow tracers showed that measurements of tracer retention underestimate MBF, indicating that high myocardial tracer extraction is a prerequisite for the simplified quantification strategies to work (12,18,(26)(27)(28)(29). The extraction of flurpiridaz F 18 in an isolated perfused rat heart has been shown to be high, independently of the flow (30).…”

mentioning

confidence: 99%

Simplified Quantification of Myocardial Flow Reserve with flurpiridaz F 18: Validation with Microspheres in a Pig Model

Sherif¹,

Nekolla²,

Saraste³

et al. 2011

J Nucl Med

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The novel PET flow tracer flurpiridaz F 18 shows high myocardial extraction and slow washout. flurpiridaz F 18 PET data analysis with tracer kinetic modeling provides accurate absolute myocardial blood flow (MBF) measurements but requires in-scanner injection and complex processing. We evaluated the hypothesis that myocardial retention and standardized uptake values (SUVs) based on late uptake provide accurate estimates of myocardial flow reserve (MFR) and, thus, might allow simplified quantification after tracer injection outside the scanner. Methods: Nine pigs had dynamic PET scans after repeated injections of flurpiridaz F 18 at rest and combined adenosine and dobutamine stress. flurpiridaz F 18 PET with a 3-compartment model and coinjected radioactive microspheres were used to delineate MBF. These quantitative measurements were compared with myocardial retention (%/min) and SUV of flurpiridaz F 18 after summing data over 5-10, 5-12, 5-15, 10-15, and 10-20 min after tracer injection. Results: MBF ranged from 0.5 to 2.8 mL/min/g. There was a good correlation between both flurpiridaz F 18 retention and SUVs from 5 to 12 min after injection and MBF measured using 3-compartment modelor microsphere-derived MBF (r 5 0.73, P , 0.05, and r 5 0.68, P , 0.05, respectively, for retention; r 5 0.88, P , 0.001, and r 5 0.92, P , 0.001, respectively, for SUV). At later time points, retention and SUV underestimated stress microsphere flow (at 10-20 min: r 5 0.41, P 5 not significant, and r 5 0.46, P 5 not significant, respectively, for retention; r 5 0.41, P 5 not significant, and r 5 0.65, P , 0.05, respectively, for SUV). When measured 5-12 min after injection, there was a close agreement between MFR measured with either flurpiridaz F 18 retention or SUV and MFR measured using microspheres (mean difference, 20.08 6 0.36 and 20.18 6 0.25, respectively). Conclusion: Myocardial retention and SUVs of the 18 F-labeled flow tracer flurpiridaz F 18 accurately reflect the MFR. These simplified analysis methods may facilitate the combination of quantitative assessment of perfusion reserve and rapid clinical imaging protocols. Myocardi al perfusion imaging with SPECT and PET is a standard tool for detection of coronary artery disease, risk stratification of patients, and guidance of therapeutic interventions (1-4). Usually, myocardial perfusion is analyzed in a qualitative manner, so that only relative perfusion changes can be detected. Absolute quantification of myocardial blood flow (MBF) and the subsequent calculation of myocardial flow reserve (MFR; the ratio of MBF at stress and rest) are a goal of essentially all invasive and noninvasive imaging approaches (4-8). Compared with qualitative analysis, quantitative assessment of perfusion can improve the accuracy with which coronary artery disease is detected. It can reduce the number of false-negative results in patients with multivessel disease, for which qualitative analysis often cannot uncover globally reduced perfusion or uncovers only the coronary territory supplied by the...

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“…Based on the same mechanism, another Mn PET radionuclide, 52m Mn ( t 1/2 = 21 min) in the form of “free” radionuclide has been used in myocardial imaging in pigs [16]. In this study, 52m Mn-PET data indicated high ratios of myocardium/lung and myocardium/blood; however, 52m Mn failed to provide a quantitative evaluation of the heart during imaging because of prominent liver uptake [16]. Likewise, even when chelated, high liver uptake as well as bile, bowel, kidneys and pancreatic uptake were observed during a biodistribution study using 54 Mn-DTPA in dogs [17].…”

Section: Longer-lived Positron Emitting Radionuclidesmentioning

confidence: 99%

“…Within the blood, the majority of Mn is bound to globulin and albumin [18]. Nonetheless, the blood retention of radiomanganese is low and does not significantly affect imaging quality [16,19] possibly due to rapid hepatobiliary clearance of Mn [20]. …”

Section: Longer-lived Positron Emitting Radionuclidesmentioning

confidence: 99%

Mapping biological behaviors by application of longer-lived positron emitting radionuclides

Zhou

Baidoo

Brechbiel

2013

Advanced Drug Delivery Reviews

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With the technological development of positron emission tomography (PET) and the advent of novel antibody-directed drug delivery systems, longer-lived positron-emitting radionuclides are moving to the forefront to take important roles in tracking the distribution of biotherapeutics such as antibodies, and for monitoring biological processes and responses. Longer half-life radionuclides possess advantages of convenient on-site preparation procedures for both clinical and non-clinical applications. The suitability of the long half-life radionuclides for imaging intact monoclonal antibodies (mAbs) and their respective fragments, which have inherently long biological half-lives, has attracted increased interest in recent years. In this review, we provide a survey of the recent literature as it applies to the development of nine-selected longer-lived positron emitters with half-lives of 9–140 hours (e.g., 124I, 64Cu, 86Y and 89Zr), and describe the biological behaviors of radionuclide-labeled mAbs with respect to distribution and targeting characteristics, potential toxicities, biological applications, and clinical translation potentials.

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Quantitative evaluation of manganese-52m as a myocardial perfusion tracer in pigs using positron emission tomography

Cited by 20 publications

References 21 publications

Applications of manganese‐enhanced magnetic resonance imaging (MEMRI) to imaging of the heart

Applications of manganese‐enhanced magnetic resonance imaging (MEMRI) to imaging of the heart

Simplified Quantification of Myocardial Flow Reserve with flurpiridaz F 18: Validation with Microspheres in a Pig Model

Mapping biological behaviors by application of longer-lived positron emitting radionuclides

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