Generator-produced copper-62-PTSM as a myocardial PET perfusion tracer compared with nitrogen-13-ammonia (original) (raw)
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Circulation, 2009
Background-Positron-emission tomography (PET) tracers for myocardial perfusion are commonly labeled with short-lived isotopes that limit their widespread clinical use. 18 F-BMS-747158-02 ( 18 F-BMS) is a novel pyridaben derivative that was evaluated for assessment of myocardial perfusion by comparison with 13 N-ammonia ( 13 NH 3 ) and with radioactive microspheres in a pig model. Methods and Results-Fourteen pigs injected with 500 MBq of 13 NH 3 or 100 to 200 MBq of 18 F-BMS underwent dynamic PET at rest and during pharmacological stress. In 8 of these pigs, 18 F-BMS was injected during stress combined with transient, 2.5-minute constriction of the left anterior descending coronary artery. Radioactive microspheres were coinjected with 18 F-BMS. Ratios of myocardial tracer uptake to surrounding tissues were determined, and myocardial blood flow was quantified by compartmental modeling. Both tracers showed high and homogeneous myocardial uptake. Compared with 13 NH 3 , 18 F-BMS showed higher activity ratios between myocardium and blood (rest 2.5 versus 4.1; stress 2.1 versus 5.8), liver (rest 1.2 versus 1.8; stress 0.7 versus 2.0), and lungs (rest 2.5 versus 4.2; stress 2.9 versus 6.4).
Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 1993
Positron emission tomography has been shown to provide quantitative estimates of myocardial blood flow using 13N-ammonia and 15O-water. In a validation study, myocardial blood flow was noninvasively determined in 11 open-chest anesthetized dogs using dynamic positron emission tomography. The radiopharmaceuticals 13N-ammonia and 15O-water were intravenously administered and measurements were carried out at rest and following pharmacological vasodilation to assess blood flow over a range from 53 to 580 ml/100 g/min. Quantification of blood flow based on tracer kinetic modeling of 13N-ammonia data correlated closely with myocardial blood flow determined by microspheres (y = 0.944 x +7.22, r = 0.986) and with the 15O-water injection technique y = 1.054 x -15.8 (r = 0.99). The use of 13N-ammonia with positron emission tomography enables the accurate quantification of myocardial blood flow. Using this technique, uncomplicated study protocols simplify the measurement procedures while provi...
Circulation, 1993
Background. Noninvasive assessment of regional myocardial perfusion at rest and after stress is important for the objective evaluation of the effects of coronary artery disease and its response to therapy. Centers that do not have cyclotrons rely on generator-produced radioisotopes for assessment of regional myocardial perfusion with positron emission tomography (PET). The aim of the present study was to develop and implement an approach to quantify regional myocardial perfusion using copper(II) pyruvaldehyde bis-(N4-thiosemicarbazone) (PTISM) labeled with the generator-produced, positron-emitting radionuclide 62Cu (t1,2=9.7 minutes). Methods and Results. Regional perfusion was estimated from dynamic PET scans after intravenous administration of 62Cu-PTSM in 21 studies in 13 intact dogs evaluated over a wide range of myocardial flow values. In 15 interventions in nine dogs, regional perfusion was also estimated with H215O. Regional perfusion with 62Cu-PISM was estimated from dynamic blood and tissue time-activity curves, along with the model parameter k, (forward rate of transport) and the PET parameter FBM (fraction of blood pool activity observed in tissue), using a two-compartment kinetic model. Arterial blood activity was corrected for red blood cell-associated '2Cu. In 44 comparisons, estimates of regional perfusion with 62Cu-PISM correlated well with estimates obtained with concomitantly administered radiolabeled microspheres (y=0.90x-f-0.15, r=0.95, p<0.05) over a flow range from 0.23 to 6.14 ml/g per minute. In five healthy human volunteers evaluated at rest with H215O and 62Cu-PTSM, regional perfusion estimated with 62Cu-PTSM was not significantly different from that obtained with H2`50 (1.05+±0.36 versus 0.96±0.28 ml/g per minute). '2Cu-PTSM provided high-quality images of the heart. Conclusions. The results of this study demonstrate that quantification of regional myocardial perfusion is feasible using generator-produced 62Cu-PTSM. Since 62Cu-PTSM can be used to estimate perfusion in the brain, kidney, and tumors as well as in the heart, it is an attractive tracer for centers that rely on generator-produced tracers for the evaluation of perfusion with PET. (Circulation 1993;87:173-183) KEY WORDs * blood flow, myocardial * radionuclides * radiotracers * modeling, mathematical Q uantification of regional myocardial perfusion in absolute terms (i.e., ml/g per minute) is important for the objective evaluation of myocardial perfusion and perfusion reserve in patients with coronary artery disease, assessment of the effects of therapy, and the evaluation of patients in whom abnormalities of myocardial perfusion are homogeneous (i.e.,
Quantitative Evaluation of Myocardial Blood Flow with [13N]Ammonia
Cardiology, 1997
To evaluate myocardial blood flow (MBF) and cardiac function with a single dose of 13 NH 3 , electrocardiographically (ECG) gated PET acquisition was performed after a dynamic PET scan was obtained. Gated blood-pool (GBP) imaging with C 15 O PET was also performed to compare the left ventricular ejection fraction (LVEF) obtained using the 2 methods. Methods: Six healthy volunteers and 34 patients with cardiovascular disease were studied. Each subject underwent dynamic PET scanning after a slow intravenous injection of approximately 740 MBq 13 NH 3 , followed by ECG gated PET scanning. MBF images were calculated by the Patlak plot method. Before obtaining the 13 NH 3 scan, the GBP image was obtained with a bolus inhalation of C 15 O. Twenty patients also underwent left ventriculography (LVG) to compare the value of the LVEF obtained using this technique with that determined using the gated PET method. Results: The mean regional value of MBF calculated for healthy volunteers in the resting condition was 0.61 Ϯ 0.10 mL/min/g. The LVEF obtained using GBP PET (EF CO) was consistent with that obtained using LVG. The LVEF calculated from gated 13 NH 3 scans (EF NH3) correlated well with EF CO , although EF NH3 slightly underestimated the LVEF (EF NH3 ϭ 0.97. EF CO Ϫ 2.94; r ϭ 0.87). EF NH3 was significantly different from EF CO in patients with a perfusion defect in the cardiac wall (EF NH3 ϭ 39% Ϯ 11% vs. EF CO ϭ 45% Ϯ 11%; n ϭ 19; P Ͻ 0.001), whereas no significant difference was found between them in subjects with no defect (EF NH3 ϭ 58% Ϯ 13% vs. EF CO ϭ 61% Ϯ 10%; n ϭ 21). Conclusion: Gated PET acquisition accompanied by obtaining a dynamic PET scan with a single dose of 13 NH 3 is a promising method for the simultaneous clinical evaluation of MBF and cardiac function. However, in patients with a defect in the cardiac wall, EF NH3 showed a tendency to underestimate the EF compared with EF CO .
European Journal of Nuclear Medicine, 2001
We simultaneously determined global myocardial blood flow (MBF) by the argon inert gas technique and by nitrogen-13 ammonia positron emission tomography (PET) to validate PET-derived MBF values in humans. A total of 19 patients were investigated at rest (n=19) and during adenosine-induced hyperaemia (n=16). Regional coronary artery stenoses were ruled out by angiography. The argon inert gas method uses the difference of arterial and coronary sinus argon concentrations during inhalation of a mixture of 75% argon and 25% oxygen to estimate global MBF. It can be considered as valid as the microspheres technique, which, however, cannot be applied in humans. Dynamic PET was performed after injection of 0.8±0.2 GBq 13 N-ammonia and MBF was calculated applying a two-tissue compartment model. MBF values derived from the argon method at rest and during the hyperaemic state were 1.03±0.24 ml min -1 g -1 and 2.64±1.02 ml min -1 g -1 , respectively. MBF values derived from ammonia PET at rest and during hyperaemia were 0.95±0.23 ml min -1 g -1 and 2.44±0.81 ml min -1 g -1 , respectively. The correlation between the two methods was close (y=0.92x+0.14, r=0.96; P<0.0001). No indication was found for limited extraction of ammonia in the myocardium. The high concordance of global MBF values derived with argon and ammonia indicates that the implicit correction of spillover and recovery effects, incorporated in the model by including an effective blood volume parameter, works correctly quantitatively. Our data provide the previously missing human validation of MBF measurements from 13 N-ammonia PET.
Diagnostic Value of 13N-Ammonia Myocardial Perfusion PET: Added Value of Myocardial Flow Reserve
Journal of Nuclear Medicine, 2012
The ability to obtain quantitative values of flow and myocardial flow reserve (MFR) has been perceived as an important advantage of PET over conventional nuclear myocardial perfusion imaging (MPI). We evaluated the added diagnostic value of MFR over MPI alone as assessed with 13 N-ammonia and PET/CT to predict angiographic coronary artery disease (CAD). Methods: Seventy-three patients underwent 1-d adenosine stress-rest 13 N-ammonia PET/CT MPI, and MFR was calculated. The added value of MFR as an adjunct to MPI for predicting CAD (luminal narrowing $ 50%) was evaluated using invasive coronary angiography as a standard of reference. Results: Per patient, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of MPI for detecting significant CAD were 79%, 80%, 91%, 59%, and 79%, respectively. Adding a cutoff of less than 2.0 for global MFR to MPI findings improved the values to 96% (P , 0.005), 80%, 93%, 89% (P , 0.005), and 92% (P , 0.005), respectively. Conclusion: The quantification of MFR in 13 N-ammonia PET/CT MPI provides a substantial added diagnostic value for detection of CAD. Particularly in patients with normal MPI results, quantification of MFR helps to unmask clinically significant CAD.
Journal of Nuclear Cardiology, 2005
Background. Measurement of myocardial blood flow (MBF) by dynamic nitrogen 13 ammonia (NH 3) positron emission tomography (PET) uses tracer kinetic modeling to analyze time-activity curves. We compared 2 commonly used models with 2 compartments (2C) and 3 compartments (3C) for quantification of MBF and coronary flow reserve (CFR). Methods and Results. Seventy-seven patients underwent NH 3 PET at rest and during hyperemia. Time-activity curves for blood pool and myocardial segments were obtained from short-axis images of dynamic sequences. Model fitting of the 2C and 3C models was performed to estimate regional MBF. MBF values calculated by 2C and 3C models were 0.98 ؎ 0.31 mL • min ؊1 • g ؊1 and 1.11 ؎ 0.37 mL • min ؊1 • g ؊1 , respectively, at rest (P < .0001) and 2.79 ؎ 1.18 mL • min ؊1 • g ؊1 and 2.46 ؎ 1.02 mL • min ؊1 • g ؊1 , respectively, during hyperemia (P < .01), resulting in a CFR of 3.02 ؎ 1.31 and 2.39 ؎ 1.15 (P < .0001), respectively. Significant correlation was observed between the 2 models for calculation of resting MBF (r ؍ 0.78), hyperemic MBF (r ؍ 0.68), and CFR (r ؍ 0.68). Conclusion. Measurements of MBF and CFR by 2C and 3C models are significantly related. However, quantification of MBF and CFR significantly differs between the methods. This difference needs to be considered when normal values are established or when measurements obtained with different methods need to be compared.
Evaluation of 68Ga-labeled tracers for PET imaging of myocardial perfusion in pigs
2012
We evaluated four potential gallium-68 (68 Ga)-labeled tracers for positron emission tomography (PET) imaging of myocardial perfusion in comparison with oxygen-15-labeled water ([ 15 O]water) in healthy pigs. Four hexadentate salicylaldimine ligands derived from bis(3-aminopropyl)ethylenediamine (BAPEN) that showed promise in previous rat experiments were selected for this study. Methods: Following an evaluation of myocardial blood flow with [ 15 O]water PET, the pigs (total n=14) underwent a dynamic 90-min PET study with one of four 68 Ga-labeled BAPEN derivatives (n=3-5 per tracer) either at rest or under adenosine stress. Serial arterial blood samples were collected during the imaging for the measurements of total radioactivity, radiometabolites, plasma protein binding and blood-to-plasma ratio for the 68 Ga chelates. Time-activity curves of the left ventricular blood pool and myocardium were derived from PET images, and metabolite-corrected arterial input function was used for kinetic modeling. Also, ex vivo biodistribution of 68 Ga radioactivity was analyzed. Results: All four 68 Ga tracers showed undesirably slow myocardial accumulation over time, but their in vivo stability, clearance from blood and the kinetics of the myocardium uptake varied. [ 68 Ga][Ga-(sal) 2 BAPDMEN] 1+ showed the highest myocardial uptake in PET images and tissue samples (myocardium-to-blood ratio 7.63±1.89, myocardium-to-lung ratio 3.03±0.33 and myocardium-to-liver ratio 1.80±0.82). However, there was no correlation between the myocardial perfusion measured with [ 15 O]water and the net uptake rates or K 1 values of the 68 Ga chelates. Conclusion: Our results revealed that myocardial accumulation of the 68 Ga chelates proposed for myocardial perfusion imaging with PET was slow and not determined by myocardial perfusion in a large animal model. These findings suggest that the studied tracers are not suitable for clinical imaging of myocardial perfusion.
Cardiac PET perfusion tracers: current status and future directions
Seminars in nuclear medicine, 2014
PET myocardial perfusion imaging (MPI) is increasingly being used for noninvasive detection and evaluation of coronary artery disease. However, the widespread use of PET MPI has been limited by the shortcomings of the current PET perfusion tracers. The availability of these tracers is limited by the need for an onsite ((15)O water and (13)N ammonia) or nearby ((13)N ammonia) cyclotron or commitment to costly generators ((82)Rb). Owing to the short half-lives, such as 76 seconds for (82)Rb, 2.06 minutes for (15)O water, and 9.96 minutes for (13)N ammonia, their use in conjunction with treadmill exercise stress testing is either not possible ((82)Rb and (15)O water) or not practical ((13)N ammonia). Furthermore, the long positron range of (82)Rb makes image resolution suboptimal and its low myocardial extraction limits its defect resolution. In recent years, development of an (18)F-labeled PET perfusion tracer has gathered considerable interest. The longer half-life of (18)F (109 minu...