Story of Rubidium-82 and Advantages for Myocardial Perfusion PET Imaging

Abstract

Rubidium-82 has a long story, starting in 1954. After preclinical studies in dogs showing that myocardial uptake of this radionuclide was directly proportional to myocardial blood flow (MBF), clinical studies were performed in the 80s leading to an approval in the USA in 1989. From that time, thousands of patients have been tested and their results have been reported in three meta-analyses. Pooled patient-based sensitivity and specificity were, respectively, 0.91 and 0.90. By comparison with (99m)Tc-SPECT, (82)Rb PET had a much better diagnostic accuracy, especially in obese patients with body mass index ≥30 kg/m(2) (85 versus 67% with SPECT) and in women with large breasts. A great advantage of (82)Rb PET is its capacity to accurately quantify MBF. Quite importantly, it has been recently shown that coronary flow reserve is associated with adverse cardiovascular events independently of luminal angiographic severity. Moreover, coronary flow reserve is a functional parameter particularly useful in the estimate of microvascular dysfunction, such as in diabetes mellitus. Due to the very short half-life of rubidium-82, the effective dose calculated for a rest/stress test is roughly equivalent to the annual natural exposure and even less when stress-only is performed with a low activity compatible with a good image quality with the last generation 3D PET scanners. There is still some debate on the relative advantages of (82)Rb PET with regard to (99m)Tc-SPECT. For the last 10 years, great technological advances substantially improved performances of SPECT with its accuracy getting closer to this of (82)Rb/PET. Currently, the main advantages of PET are its capacity to accurately quantify MBF and to deliver a low radiation exposure.

Keywords: PET imaging; myocardial perfusion; rubidium-82.

Figure 1

A 56-year-old woman with a history of obesity (BMI: 31.2 cm/kg²), hypertension, hyperlipemia, and type 2 diabetes complicated of retinopathy and renal failure. The patient was referred to the Nuclear Medicine department for detection of coronary artery disease and underwent both Tc-99m-sestamibi SPECT (D-SPECT, Spectrum Dynamics, Haifa) and rubidium-82 PET/CT (Discovery 690 VCT, GEMS, Buc, France) as part of a clinical trial. SPECT (93% of the predicted maximal heart rate, no symptoms, EKG positive) was normal with a homogeneous uptake of the tracer both at stress and at rest (A). ⁸²Rb PET performed after Dipyridamole infusion showed a mild decrease of the tracer uptake in the lateral wall (arrow), completely reversible at rest, raising the suspicion of ischemia in the territory of the circumflex artery (B). This hypothesis was then confirmed by quantitative data derived from myocardial blood flow measurement with a coronary steal phenomenon in the same territory [coronary flow reserve (CFR) <1; (C)]. In addition, the CFR was markedly decreased (<1.5) in the territory of both the left descending artery and the right coronary artery, suggesting the presence of significant stenosis of these two coronary arteries. The coronary angiography confirmed the diagnosis of three-vessel disease and the patient underwent surgical revascularization. This case report underlines the greatest sensitivity of ⁸²Rb PET over SPECT in the setting of balanced ischemia, in relation with the ability to perform absolute quantification of myocardial blood flow.