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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 providing excellent qualitative and quantitative information.

Objectives: The aim of this study was to define the temporal changes in the relationship between technetium-99m teboroxime tissue retention and myocardial blood flow in a canine model., Background: Technetium-99m teboroxime is a new neutral lipophilic myocardial perfusion agent. It is known to be highly extracted by the myocardium but to have a rapid clearance rate., Methods: A wide range of myocardial blood flow was induced in each experiment by regional coronary occlusion and dipyridamole infusion. Myocardial retention of technetium-99m teboroxime was determined by in vitro tissue counting at 1, 2 or 5 min after injection of the tracer. Tracer retention was correlated with microsphere-determined blood flow and the data were fitted to nonlinear functions., Results: Correlation coefficients for these functions were 0.92, 0.95 and 0.95 at 1, 2, and 5 min, respectively. At 1 min after injection, the relationship of technetium-99m teboroxime retention to blood flow was linear over a wide flow range, becoming nonlinear at flow rates greater than 4.5 ml/min per g. After 5 min the retention-flow relationship was linear only to 2.5 ml/min per g, above which little change in retention was noted. Normalized myocardial retention, expressed as a percent of the retention at 1 ml/min per g, was also calculated. At flow rates of 1, 2, 3, 4 and 5 ml/min per g, normalized retention was 100, 169, 228, 277 and 317% at 1 min and 100, 171, 217, 239 and 237% at 5 min after injection., Conclusions: At 1 min after injection, the relationship of technetium-99m teboroxime myocardial retention to blood flow is well maintained over a wide range of flow. However, after only 5 min, tracer retention underestimates flow changes at moderate and high flow rates. Thus, rapid acquisition protocols are necessary to fully exploit the potential of this promising new tracer in the evaluation of myocardial perfusion.

Copper-62-labeled pyruvaldehyde bis(N-4-methylthiosemicarbazone) copper(II) (PTSM) is a generator-produced myocardial perfusion tracer. Animal studies have shown high myocardial tissue extraction and prolonged retention. The aim of this study was to define myocardial kinetics of 62Cu-PTSM and to determine its suitability for evaluating myocardial perfusion at rest and during pharmacological vasodilation in human subjects. In six healthy volunteers, 62Cu-PTSM was administered at baseline and during a 6-min adenosine infusion (140 micrograms/kg/min). Dynamic PET imaging with high temporal resolution was performed over 20 min. Good image quality was observed at rest and following adenosine. Myocardial kinetics demonstrated prolonged tissue retention with a clearance half-life of 105 +/- 49 min at rest and 101 +/- 65 min following adenosine (p = ns). Copper-62-PTSM tissue retention was quantified and showed only a 1.97-fold increase from rest to adenosine studies. This suggests attenuation of tracer retention at high flow rates. Copper-62-PTSM represents a promising new radiopharmaceutical for the evaluation of myocardial perfusion in the human heart.

Positron emission tomography (PET) represents an advanced imaging technology for the noninvasive evaluation of regional myocardial blood flow. Several blood flow tracers are available, including cyclotron-produced radiopharmaceuticals such as [15O]H2O and [13N]NH3 and generator-produced rubidium-82 ([82Rb]-) and copper-62 ([62Cu]-) pyruvaldehyde-bis-(N-4-methylthiosemicarbazone) (PTSM). 82Rb and [13N]NH3 are the most commonly employed tracers for the qualitative evaluation of regional myocardial perfusion. Their use allows the accurate detection of coronary artery disease in combination with pharmacologic stress. Initial comparative studies with thallium-201 (201Tl) single-photon emission computed tomography (SPECT) have shown that PET has a higher diagnostic accuracy. Beyond improved diagnostic performance, the quantitative flow measurements provided by PET represent an important advance in nuclear cardiology. The radiopharmaceuticals [15O]H2O and [13N]NH3 have been applied for the noninvasive determination of regional coronary reserve. Quantification of blood flow based on tracer kinetic modeling yields blood flow values in close agreement with determinations provided by invasive procedures. The noninvasive quantification of blood flow provides a useful research and clinical tool for the objective assessment of therapeutic interventions as well as pathophysiologic alterations of regional myocardial blood flow in various cardiac diseases.

L-3-[123I]iodo-alpha-methyltyrosine (123IMT) like tyrosine has been reported previously to have a high affinity for a transport system in the blood-brain-barrier (BBB). We examined the kinetic behavior of 124IMT in brain and plasma in two patients with glioblastoma using dynamic positron emission tomography (PET). 124IMT accumulated in brain and tumor tissue, reaching a maximum after 15 min, with a washout of 20% to 35% at 60 min postinjection. Animal experiments confirmed the accumulation of the intact tracer in murine brain, but there was no incorporation into proteins. SPECT studies with 123IMT in patients with different types of brain tumors showed increased uptake in 26 of 32 tumors. Although nonspecific uptake in tumors must be considered, the accumulation of IMT in normal brain and in some tumors with intact BBB suggests a specific uptake of IMT. As transport is the main determinant of initial amino acid uptake, 123IMT appears to be a suitable SPECT tracer of amino acid uptake although it is not incorporated into protein.