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While there are several myocardial tracers available for PET imaging, only three are presently used for clinical imaging: rubidium-82 (Rb-82), N-13 ammonia (N-13), and fluorine-18 (18F) fluorodeoxyglucose (FDG). For complete review of PET isotopes, see Chapter 3.
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Rubidium (Rb)-82 is a potassium analog radiopharmaceutical that is produced with commercially available generators which can be stored on site. It is produced by the decay of strontium-82 (82Sr) which has a half-life of 25.5 days. Rb-82 has a half-life of 75 seconds. The extraction fraction of Rb-82 is estimated to be 65% to 75%, substantially higher than SPECT technetium agents.
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The use of Rb-82 is provided by an on-site generator and delivery system, which can be stored conveniently in the camera room. The generator is replaced every 4 to 6 weeks and supplied at a fixed cost, independent of the number of studies performed. Because of the cost involved with the generator, consideration for PET use in a facility should include adequate patient volumes. When in use, the generator is replenished quickly, within 10 minutes via 82Sr to Rb-82 decay. This permits minimal downtime between stress and rest imaging, allowing efficient utilization of the generator. The protocol for stress imaging requires the use of a pharmacologic stress agent because of the short half-life of Rb-82.
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Advantages of Rb-82 include the ability to have rapid acquisition times for rest and stress imaging and continuous availability. Another advantage was studied by Parkash et al.3 They used Rb-82 with PET/CT imaging and were able to detect smaller perfusion abnormalities and more accurate detecting multivessel disease. This suggests that PET may be able to detect multivessel disease more accurately than with SPECT-imaging techniques.4
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There are also disadvantages to Rb-82 imaging. Due to the half-life of 82Sr, the same generator is used for 4 to 6 weeks, but with reduced activity during the last weeks, which can impact image quality, with cameras using 2D acquisition. This limitation, however, can be overcome by 3D imaging.5 The short half-life of rubidium limits its clinical use to pharmacologic stress and not exercise.
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N-13 has been used as a cardiac tracer for over 20 years. Implementation requires the presence of an on-site cyclotron as it has a half-life of 9.96 minutes. N-13 has an extraction fraction of up to 80%. The overall trapping of N-13 is dependent on a properly functioning metabolism and trapping may be decreased in myocytes that are ischemic.6,7 Advantages of N-13 ammonia include the high tomographic counts and a clear blood-to-myocardial delineation. Because of the longer half-life, exercise is possible, in contrast to rubidium. Limitations include the finding that even in normal subjects, the retention of N-13 in the lateral wall is 10% less than other segments creating false-positive results.8 Prominent liver activity in some studies can complicate interpretation of the inferior wall.9 Finally, the necessity for on-site or close proximity cyclotron availability due to short half-life limits its practical use. This has severely limited its use, with perhaps 15 to 20 laboratories using this agent according to recent data. This may change with the availability of a small cyclotron designed for ammonia production only that is much more manageable and can be placed onsite.
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Fluorine-18 Fluorodeoxyglucose
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FDG is fluorine-labeled with 2-deoxyglucose. It is cyclotron produced and decays into O-18 oxygen. When it decays, its positron range is very short (0.5 mm). This fact, combined with its half-life of 109.8 minutes, allows it to provide images with the highest spatial resolution of any of the commonly used radionuclides.
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FDG is a glucose analog and is brought into the myocardium via diffusion across glucose-specific transporters that are located on the myocytes. Once in the cell, it is transformed into FDG-6-P. There are low levels of glucose-6-phosphatase to reverse this step; there the FDG-6-P is essentially trapped in the myocardial cell. The use of F-18-FDG is further elaborated on the viability discussion later in the chapter as well as Chapter 21. Active research is underway to validate F-18 Flurpiridaz, a blood flow agent for the detection of CAD.