Review Article
Properties of an ideal PET perfusion tracer: New PET tracer cases and data

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Abstract

An ideal positron emission tomography (PET) tracer should be highly extractable by the myocardium and able to provide high-resolution images, should enable quantification of absolute myocardial blood flow (MBF), should be compatible with both pharmacologically induced and exercise-induced stress imaging, and should not require an on-site cyclotron. The PET radionuclides nitrogen-13 ammonia and oxygen-15 water require an on-site cyclotron. Rubidium-82 may be available locally due to the generator source, but greater utilization is limited because of its relatively low myocardial extraction fraction, long positron range, and generator cost. Flurpiridaz F 18, a novel PET tracer in development, has a high-extraction fraction, short positron range, and relatively long half-life (as compared to currently available tracers), and may be produced at regional cyclotrons. Results of early clinical trials suggest that both pharmacologically and exercise-induced stress PET imaging protocols can be completed more rapidly and with lower patient radiation exposure than with single-photon emission computerized tomography (SPECT) tracers. As compared to SPECT images in the same patients, flurpiridaz F 18 PET images showed better defect contrast. Flurpiridaz F 18 is a potentially promising tracer for assessment of myocardial perfusion, measurement of absolute MBF, calculation of coronary flow reserves, and assessment of cardiac function at the peak of the stress response.

Introduction

Positron emission tomography (PET) myocardial perfusion imaging (MPI) has been technically feasible for many years, but wide acceptance has been hindered by the requirement for an on-site cyclotron to generate the radiotracers, the drawbacks of available radiotracers, limited numbers of PET scanners, and financial considerations. With the increasing availability of better cameras, more consistent reimbursement, and the availability of tracers that do not require an on-site cyclotron, these limitations are being addressed.

Section snippets

PET Myocardial Perfusion Tracers

Nitrogen-13 ammonia (13NH3) and oxygen-15 water (H215O) are excellent PET tracers,1,2 but few clinical sites have the on-site cyclotron required to produce them. The introduction of rubidium-82 (82Rb),3 which can be produced locally with a generator, expanded the reach of PET MPI into more hospitals and imaging centers. Rubidium-82, however, is not an ideal tracer. The high and recurring cost of the generator requires a high patient volume to make its use cost-effective. Image resolution with 82

Clinical Studies with Flurpiridaz F 18

Phase 1 and Phase 2 clinical studies have been completed with flurpiridaz F 18, and Phase 3 studies are currently ongoing.

Preliminary Comparison of Flurpiridaz F 18 PET and 99mTc SPECT Imaging

The author summarizes here his experience with 9 patients enrolled at the UCLA Medical Center. Perfusion abnormalities were detected by both SPECT and PET in 6 patients who had abnormal angiography results. Angiography results from the remaining 3 patients were normal, and no perfusion abnormalities were detected with PET in any of the 3 patients. SPECT images demonstrated that 2 of the 3 angiographically normal patients had no perfusion abnormalities, but detected an abnormality in the third

Preliminary Results of Absolute Quantification of MBF Using Flurpiridaz F 18

Absolute quantification of MBF with PET represents a major advantage over SPECT MPI and is a potential “game-changer” in the noninvasive evaluation of CAD. Decades of studies with 13NH3 and H215O have shown that absolute quantification of MBF allows better identification of multivessel disease, assessment of the severity of microvascular disease, and also allows evaluation of endothelial dysfunction and responses to treatment.18 One of the limitations of imaging relative perfusion (as is done

Conclusion

Wider utilization of PET myocardial perfusion imaging has been limited by the choice of available radiopharmaceuticals. Of those currently in use, 13NH3 and H215O require an on-site cyclotron, and thus are impractical for widespread utilization. Rubidium-82 may be prepared on site using a generator. But because of its long positron range, low myocardial extraction fraction, short half-life, incompatibility with exercise-stress imaging, and high recurrent costs, 82Rb has proved to be a

Disclosure

Dr Maddahi reported receiving grant support from Lantheus Medical Imaging. He reported being part of the speakers’ bureau with Astellas Pharmaceuticals. He reported being part of the advisory board for Digirad Corporation, Lantheus Medical Imaging, and Astellas Pharmaceuticals. He reported receiving honoraria from Digirad Corporation and Lantheus Medical Imaging.

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