On “ruby” in myocardial perfusion imaging

Sir,

I would like to comment on rubidium (Rb)-82 positron emission tomography (PET) in myocardial perfusion imaging. ⁸²Rb PET-CT is state of the art in quantifying myocardial blood flow (MBF) and it also gives important prognostic information apart from risk stratification and according management. 3D ⁸²Rb-PET shows highly reproducible same-day repeated measurements of data acquisition of MBF at rest and is sensitive to detect small, serial changes in rest MBF.[1] MBF thus measured is known to correlate over a wide range of flows with 2D ¹⁵O-water PET as standard MBF measurements.[2] The perfusion patterns of stress ⁸²Rb-PET using regadenoson also correlate highly with the current dipyridamole imaging protocol. Left ventricular ejection fraction reserve during dipyridamole or regadenoson ⁸²Rb-PET is inversely related to ischemic burden and is a marker of multivessel CAD.[3] These observations are known to correspond clinically too as depicted in a study where dynamic ⁸²Rb measurements provided estimates of MBF (as tested by radiolabelled microspheres) in stunned and acutely and chronically infarcted tissue at rest and during hyperemia.[4] Predictors of a lower stress/rest MBF ratio (with an apparently normal ⁸²Rb-PET) are age, smoking, and coronary artery calcium scoring (CACS) > 400, diabetes, hypertension, and lower BMI.[5] ⁸²Rb is also known to gauge endothelial dysfunction. MBF measurements with ⁸²Rb detected coronary endothelial dysfunction in smokers comparable to ¹⁵O-water PET (cold-pressor test).[6]

⁸²Rb-PET is shown to improve the cardiac-death risk stratification in coronary artery disease (CAD) patients. In a rest-stress ⁸²Rb PET MPI (myocardial perfusion imaging) the size of rest, and stress-induced perfusion defects measured in percentage of the left ventricular (LV) myocardium, grouped into 0%, 0-5%, 5-10%, 10-20%, and >20% pointed to annual cardiac mortality rates across stress perfusion defect size as 0.4%, 0.9%, 1.0%, 2.2%, and 3.2% respectively.[7] ⁸²Rb-PET MPI reclassified 15% of individuals into more appropriate cardiac death risk strata along with the reclassification of intermediate (36%) and high (30%) pre-PET risk groups.[7] In a low-risk chest pain population, cardiac ⁸²Rb-PET had true-positive cardiac catheterization rates comparable to prior studies of SPECT sestimibi imaging and coronary CTA imaging.[8] Likewise serial ⁸²Rb-PET MPI shows that for each 5% improvement in defect size (after revascularization) between scans, there is a 20% improvement in risk of both all-cause and cardiac-specific mortality.[9]

⁸²Rb-PET/CT also helps gauge the incidence of major adverse cardiac events (MACE) such as cardiac death, myocardial infarction, revascularization or hospitalization for cardiac-related event. In a study on patients with known or suspected CAD who underwent both a rest and adenosine stress cardiac ⁸²Rb PET/CT, annualized MACE rate was higher in those with ischemia compared to those without ischemia (60% vs. 8%). Those with lowest myocardial flow reserve (MFR) tertile (MFR<1.7) had higher MACE rate than the two highest tertiles (44% vs. 9% and 12%).[10] Cross sectional area (CSA) measurement with computed tomography angiography (CTA) of ≤1.35 mm² has a sensitivity of 91% and specificity of 54% for predicting ⁸²Rb MFR < 2; and a sensitivity of 64% and a specificity of 91% for predicting severely impaired ⁸²Rb MFR (< 1.5).[11]

⁸²Rb is easily available, has a fixed cost, enables high patient throughput with faster and easier qualitative evaluation of MBF and can be scheduled in emergencies unlike ¹³N ammonia. Although ¹³N ammonia may get better resolution than ⁸²Rb (owing to lower mean positron range), the logistical burden of coordination and the requirement of an onsite cyclotron apart from necessitating synchronization by numerous staff may limit its use.[12] ¹⁵O-water also has high patient throughput, very low radiation burden and is generally considered a better MBF tracer (metabolically inert, freely diffusible, complete first-pass extraction and absence of washout in scar tissue) but it has low contrast between myocardium and blood in dynamic images (low signal-to-noise ratios of scans) and requires kinetic analysis and an on-site cyclotron.[13]

⁸²Rb is not without limitations. Being an uptake tracer, it might not differentiate between viable myocardium and scar tissue. Its low uptake and that it is not linearly dependent on MBF may lead to underestimation of MBF warranting high correction factors. These correction factors extrapolated from animal models may be inaccurate in humans and they may also increase noise levels. Additionally active uptake by the cell, might cause the several pathophysiological processes influence ⁸²Rb.[13] Concerns of contamination with radioactive elements have also been raised against ⁸²Rb especially after the documented incident of radiation exposure of about 90 mSv (normally 2.8 mSv) in two patients. Investigation pointed to contamination of ⁸²Rb (CardioGen-82) with strontium (⁸²Sr and ⁸⁵Sr).[14] Although it may be an isolated event, better/reliable generator performance and monitoring for such radiation activity are warranted.

⁸²Rb PET is certainly an invaluable tool in tracking CAD and guiding therapeutic management for risk minimization.