Review on New targets of nuclear cardiology

Nkoulou R, Pazhenkottil AP, Kuest SM, et al. Semiconductor detectors allow low-dose-low-dose 1-day SPECT myocardial perfusion imaging. J Nucl Med. 2011;52:1204-9.

Cadmium zinc telluride (CZT) detectors with linear counting rate response enable count subtraction in sequential scanning. With this hypothesis in mind, the Authors evaluated whether count subtraction eliminated the need for higher activity doses in the second part of the 1-d stress-rest myocardial perfusion imaging (MPI) protocol. To this purpouse, the Authors studied 50 patients (mean age ± SD, 66 ± 12 y) with visually abnormal (n = 42) or equivocal (n = 8) adenosine-stress MPI (320 MBq of (99m)Tc-tetrofosmin) on a CZT camera. Rest MPI was performed with a low dose (320 MBq) and repeated after injection of an additional 640 MBq of (99m)Tc-tetrofosmin to achieve a standard 3-fold increased dose at rest (960 MBq), compared with stress (320 MBq). Low-dose rest myocardial perfusion images were reconstructed after subtracting the background activity of the preceding stress scan. Segmental percentage tracer uptake of the 2 rest myocardial perfusion images (320 vs. 960 MBq) was compared using intraclass correlation and Bland-Altman limits of agreement. Patient- and coronary territory-based clinical agreement was assessed. The standard protocol revealed ischemia in 34 (68%) and a fixed defect in 8 (16%) patients, of whom 33 (97%) and 8 (100%) were correctly identified by low-dose MPI (clinical agreement, 98%). Segmental uptake correlated well between low- and standard-dose rest scans (r = 0.94, P < 0.001; Bland-Altman limits of agreement, -11 to +11%). Defect extent was 14.4% (low-dose) versus 13.1% (standard-dose) at rest (P = not statistically significant) and 26.6% at stress (P < 0.001 vs. rest scans). The Authors suggested that accurate assessment of ischemic myocardial disease is feasible with a low-dose-low-dose 1-d SPECT MPI protocol using a CZT device.

Gimelli A, Bottai M, Genovesi D et al. High diagnostic accuracy of low-dose gated-SPECT with solid-state ultrafast detectors: preliminary clinical results. Eur J Nucl Med Mol Imaging. 2011. [Epub ahead of print]

Appropriate use of SPECT imaging is regulated by evidence-based guidelines and appropriateness criteria in an effort to limit the burden of radiation administered to patients. The Authors aimed at establishing whether the use of a low dose for stress-rest single-day nuclear myocardial perfusion imaging on an ultrafast (UF) cardiac gamma camera using cadmium-zinc-telluride solid-state detectors could be used routinely with the same accuracy obtained with standard doses and conventional cameras. To this purpose, 137 consecutive patients (mean age 61±8 years) with known or suspected coronary artery disease (CAD) were enrolled. They underwent single-day low-dose stress-rest myocardial perfusion imaging using UF SPECT and invasive coronary angiography. Patients underwent the first scan with a 7-min acquisition time 10 min after the end of the stress protocol (dose range 185 to 222 MBq of (99m)Tc-tetrofosmin). The rest scan (dose range 370 to 444 MBq of (99m)Tc-tetrofosmin) was acquired with a 6-min acquisition time. The mean summed stress scores (SSS) and mean summed rest scores (SRS) were obtained semiquantitatively. Coronary angiograms showed significant epicardial CAD in 83% of patients. Mean SSS and SRS were 10±5 and 3±3, respectively. Overall the area under the ROC curve for the SSS values was 0.904, while the areas under the ROC curves for each vascular territory were 0.982 for the left anterior descending artery, 0.931 for the left circumflex artery and 0.889 for the right coronary artery. The Authors concluded that this pilot study demonstrated the feasibility of a low-dose single-day stress-rest fasting protocol performed using UF SPECT, with good sensitivity and specificity in detecting CAD at low patient exposure, opening new perspectives in the use of myocardial perfusion in ischaemic patients.

Yu M, Nekolla SG, Schwaiger M, Robinson SP. The next generation of cardiac positron emission tomography imaging agents: discovery of flurpiridaz F-18 for detection of coronary disease. Semin Nucl Med. 2011;41:305-13.

This review compares the current preclinical and clinical data with an ideal myocardial perfusion imaging (MPI) agent profile. As a matter of fact, MPI with thallium 201 ((201)Tl) or (99m)Tc based imaging agents has become a major tool for noninvasive identification of coronary artery disease (CAD). However, single photon emission computed tomography (SPECT) imaging with the current agents is vulnerable to artifacts associated with soft tissue attenuation, proximal gastrointestinal activity, image quality, and suboptimal sensitivity and is limited by the degree of first-pass myocardial extraction. The development of (18)F-based flurpiridaz F-18 takes advantage of positron emission tomography (PET) to overcome many of the imaging issues and structural design to achieve an ideal MPI agent profile. Flurpiridaz F-18 was designed to bind to mitochondrial complex I with high affinity and demonstrates high heart uptake in multiple species with clear delineation of perfusion deficits. It exhibits rapid uptake in the myocardium, prolonged retention, and superior extraction versus flow profiles compared with (201)Tl and (99m)Tc-sestamibi. A first in man study has established the safety and dosimetry of flurpiridaz F-18 and confirmed high sustained cardiac uptake. Subsequent studies performed in CAD patients established the dose and timing needed to detect perfusion deficits when the agent is administered under rest and stress conditions. The assessment indicates flurpiridaz F-18 represents a new generation of PET MPI agents and demonstrates significantly improved molecular and imaging characteristics.

Bokhari S, Raina A, Berman Rosenweig E, et al. PET Imaging May Provide a Novel Biomarker and Understanding of Right Ventricular Dysfunction in Patients With Idiopathic Pulmonary Arterial Hypertension. Circ Cardiovasc Imaging. 2011;4:641-7.

The clinical course in pulmonary arterial hypertension (PAH) is variable, and there is limited information on the determinants and progression of right ventricular (RV) dysfunction. The objective of this study is to develop PET metabolic imaging of the RV as a noninvasive tool in patients with PAH. To this purpouse, the Authors performed PET scanning in 16 patients with idiopathic PAH (age, 41±14 years, 82% women) using (13)N-NH(3) for perfusion imaging and (18)F-fluorodeoxyglucose for metabolic imaging. The myocardium was divided into 6 regions of interest (3 left ventricular [LV], 3 RV), and time-activity curves were generated. A 2- compartment model was used to calculate myocardial blood flow (MBF), and Patlak analysis was used to calculate the rate of myocardial glucose uptake (MGU). All patients underwent cardiac catheterization, cardiac MRI, and cardiopulmonary exercise testing with gas exchange. MBF, MGU, and the ratio of RV/LV MGU were correlated to clinical parameters. Pulmonary artery (PA) pressure was 79±19/30±8 mm Hg (mean, 48±10 mm Hg). MBF was 0.84±0.33 mL/g per minute for the LV and 0.45±0.14 mL/g per minute for the RV. Mean MGU was 136±72 nmol/g per minute for the LV and 96±69 nmol/g per minute for the RV. The ratio of RV/LV MGU correlated significantly with PA systolic (r=0.75, P=0.0085) and mean (r=0.87, P=0.001) pressure and marginally with maximum oxygen consumption (r=-0.59, P=0.05). RV free wall MGU also correlated well with mean PA pressure (r=0.66, P=0.03). Due to these results, the Authors concluded that PET scanning with (13)N-NH(3) and (18)F-fluorodeoxyglucose is a feasible modality for quantifying RV blood flow and metabolism in patients with idiopathic PAH.