Clinical use of quantitative cardiac perfusion PET: rationale, modalities and possible indications. Position paper of the Cardiovascular Committee of the European Association of Nuclear Medicine (EANM).

Until recently, PET was regarded as a luxurious way of performing myocardial perfusion scintigraphy, with excellent image quality and diagnostic capabilities that hardly justified the additional cost and procedural effort. Quantitative perfusion PET was considered a major improvement over standard qualitative imaging, because it allows the measurement of parameters not otherwise available, but for many years its use was confined to academic and research settings. In recent years, however, several factors have contributed to the renewal of interest in quantitative perfusion PET, which has become a much more readily accessible technique due to progress in hardware and the availability of dedicated and user-friendly platforms and programs. In spite of this evolution and of the growing evidence that quantitative perfusion PET can play a role in the clinical setting, there are not yet clear indications for its clinical use. Therefore, the Cardiovascular Committee of the European Association of Nuclear Medicine, starting from the experience of its members, decided to examine the current literature on quantitative perfusion PET to (1) evaluate the rationale for its clinical use, (2) identify the main methodological requirements, (3) identify the remaining technical difficulties, (4) define the most reliable interpretation criteria, and finally (5) tentatively delineate currently acceptable and possibly appropriate clinical indications. The present position paper must be considered as a starting point aiming to promote a wider use of quantitative perfusion PET and to encourage the conception and execution of the studies needed to definitely establish its role in clinical practice.

Position paper of the Cardiovascular Committee of the European Association of Nuclear Medicine (EANM) on PET imaging of atherosclerosis.

Cardiovascular diseases are the leading cause of death not only in Europe but also in the rest of the World. Preventive measures, however, often fail and cardiovascular disease may manifest as an acute coronary syndrome, stroke or even sudden death after years of silent progression. Thus, there is a considerable need for innovative diagnostic and therapeutic approaches to improve the quality of care and limit the burden of cardiovascular diseases. During the past 10 years, several retrospective and prospective clinical studies have been published using (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET) to quantify inflammation in atherosclerotic plaques. However, the current variety of imaging protocols used for vascular (arterial) imaging with FDG PET considerably limits the ability to compare results between studies and to build large multicentre imaging registries. Based on the existing literature and the experience of the Members of the European Association of Nuclear Medicine (EANM) Cardiovascular Committee, the objective of this position paper was to propose optimized and standardized protocols for imaging and interpretation of PET scans in atherosclerosis. These recommendations do not, however, replace the individual responsibility of healthcare professionals to make appropriate decisions in the circumstances of the individual study protocols used and the individual patient, in consultation with the patient and, where appropriate and necessary, the patient's guardian or carer. These recommendations suffer from the absence of conclusive evidence on many of the recommendations. Therefore, they are not intended and should not be used as "strict guidelines" but should, as already mentioned, provide a basis for standardized clinical atherosclerosis PET imaging protocols, which are subject to further and continuing evaluation and improvement. However, this EANM position paper might indeed be a first step towards "official" guidelines on atherosclerosis imaging with PET.

Performance of cardiac cadmium-zinc-telluride gamma camera imaging in coronary artery disease: a review from the cardiovascular committee of the European Association of Nuclear Medicine (EANM).

The trade-off between resolution and count sensitivity dominates the performance of standard gamma cameras and dictates the need for relatively high doses of radioactivity of the used radiopharmaceuticals in order to limit image acquisition duration. The introduction of cadmium-zinc-telluride (CZT)-based cameras may overcome some of the limitations against conventional gamma cameras. CZT cameras used for the evaluation of myocardial perfusion have been shown to have a higher count sensitivity compared to conventional single photon emission computed tomography (SPECT) techniques. CZT image quality is further improved by the development of a dedicated three-dimensional iterative reconstruction algorithm, based on maximum likelihood expectation maximization (MLEM), which corrects for the loss in spatial resolution due to line response function of the collimator. All these innovations significantly reduce imaging time and result in a lower patient's radiation exposure compared with standard SPECT. To guide current and possible future users of the CZT technique for myocardial perfusion imaging, the Cardiovascular Committee of the European Association of Nuclear Medicine, starting from the experience of its members, has decided to examine the current literature regarding procedures and clinical data on CZT cameras. The committee hereby aims 1) to identify the main acquisitions protocols; 2) to evaluate the diagnostic and prognostic value of CZT derived myocardial perfusion, and finally 3) to determine the impact of CZT on radiation exposure.

Relationship between PSA kinetics and [18F]fluorocholine PET/CT detection rates of recurrence in patients with prostate cancer after total prostatectomy.

PURPOSE: The aim of the present study was to identify prostate-specific antigen (PSA) threshold levels, as well as PSA velocity, progression rate and doubling time in relation to the detectability and localization of recurrent lesions with [(18)F]fluorocholine (FC) PET/CT in patients after radical prostatectomy. METHODS: The study group comprised 82 consecutive patients with biochemical relapse after radical prostatectomy. PSA levels measured at the time of imaging were correlated with the FC PET/CT detection rates in the entire group with PSA velocity (in 48 patients), with PSA doubling time (in 47 patients) and with PSA progression (in 29 patients). RESULTS: FC PET/CT detected recurrent lesions in 51 of the 82 patients (62%). The median PSA value was significantly higher in PET-positive than in PET-negative patients (4.3 ng/ml vs. 1.0 ng/ml; p < 0.01). The optimal PSA threshold from ROC analysis for the detection of recurrent prostate cancer lesions was 1.74 ng/ml (AUC 0.818, 82% sensitivity, 74% specificity). Significant differences between PET-positive and PET-negative patients were found for median PSA velocity (6.4 vs. 1.1 ng/ml per year; p < 0.01) and PSA progression (5.0 vs. 0.3 ng/ml per year, p < 0.01) with corresponding optimal thresholds of 1.27 ng/ml per year and 1.28 ng/ml per year, respectively. The PSA doubling time suggested a threshold of 3.2 months, but this just failed to reach statistical significance (p = 0.071). CONCLUSION: In a study cohort of patients with biochemical recurrence of prostate cancer after radical prostatectomy there emerged clear PSA thresholds for the presence of FC PET/CT-detectable lesions.

Systematic review of cost-effectiveness of myocardial perfusion scintigraphy in patients with ischaemic heart disease: A report from the cardiovascular committee of the European Association of Nuclear Medicine. Endorsed by the European Association of Cardiovascular Imaging.

Coronary artery disease (CAD) is a major cause of death and disability. Several diagnostic tests, such as myocardial perfusion scintigraphy (MPS), are accurate for the detection of CAD, as well as having prognostic value for the prediction of cardiovascular events. Nevertheless, the diagnostic and prognostic value of these tests should be cost-effective and should lead to improved clinical outcome. We have reviewed the literature on the cost-effectiveness of MPS in different circumstances: (i) the diagnosis and management of CAD; (ii) comparison with exercise electrocardiography (ECG) and other imaging tests; (iii) as gatekeeper to invasive coronary angiography (ICA), (iv) the impact of appropriate use criteria; (v) acute chest pain, and (vi) screening of asymptomatic patients with type-2 diabetes. In total 57 reports were included. Although most non-invasive imaging tests are cost-effective compared with alternatives, the data conflict on which non-invasive strategy is the most cost-effective. Different definitions of cost-effectiveness further confound the subject. Computer simulations of clinical diagnosis and management are influenced by the assumptions made. For instance, diagnostic accuracy is often defined against an anatomical standard that is wrongly assumed to be perfect. Conflicting data arise most commonly from these incorrect or differing assumptions.

Reporting nuclear cardiology: a joint position paper by the European Association of Nuclear Medicine (EANM) and the European Association of Cardiovascular Imaging (EACVI).

The report of an imaging procedure is a critical component of an examination, being the final and often the only communication from the interpreting physician to the referring or treating physician. Very limited evidence and few recommendations or guidelines on reporting imaging studies are available; therefore, an European position statement on how to report nuclear cardiology might be useful. The current paper combines the limited existing evidence with expert consensus, previously published recommendations as well as current clinical practices. For all the applications discussed in this paper (myocardial perfusion, viability, innervation, and function as acquired by single photon emission computed tomography and positron emission tomography or hybrid imaging), headings cover laboratory and patient demographics, clinical indication, tracer administration and image acquisition, findings, and conclusion of the report. The statement also discusses recommended terminology in nuclear cardiology, image display, and preliminary reports. It is hoped that this statement may lead to more attention to create well-written and standardized nuclear cardiology reports and eventually lead to improved clinical outcome.

[68Ga]-albumin-PET in the monitoring of left ventricular function in murine models of ischemic and dilated cardiomyopathy: comparison with cardiac MRI.

PURPOSE: The purpose of this study is to evaluate left ventricular functional parameters in healthy mice and in different murine models of cardiomyopathy with the novel blood pool (BP) positron emission tomography (PET) tracer [68Ga]-albumin. PROCEDURES: ECG-gated microPET examinations were obtained in healthy mice, and mice with dilative (DCM) and ischemic cardiomyopathy (ICM) using the novel BP tracer [68Ga]-albumin (AlbBP), as well as [18F]-FDG microPET. Cine-magnetic resonance imaging (MRI) examination performed on a clinical 1.5-T MRI provided the reference standard measurements. RESULTS: When considering the combined group of healthy controls, DCM and ICM AlbBP-PET significantly overestimated the magnitudes of EDV (AlbBP, 181±86 µl; cine-MRI, 125±80 µl; P<0.001) and ESV (AlbBP, 136±92 µl; cine-MRI, 96±77 µl; P<0.001), whereas the EF (AlbBP, 31±16%; cine-MRI, 33±21%; P=0.910) matched closely to cine-MRI results, as did findings with [18F]-FDG. High correlations were found between the measured cardiac parameters (EDV: R=0.978, ESV: R=0.989, and LVEF: R=0.992). CONCLUSIONS: Measuring left ventricular function in mice with [68Ga]-albumin BP PET is feasible and showed a high correlation compared to cine-MRI, which was used as a reference standard.

Course of size and density of metastatic renal cell carcinoma lesions in the early follow-up of molecular targeted therapy.

OBJECTIVE: Imaging-based monitoring of molecular therapies in oncology remains a challenge. Molecular therapies might have more pronounced effects on lesion density than on lesion size. We analyzed changes in lesion diameter and density in patients with metastasized renal cell cancer (mRCC) in the early follow-up of targeted therapy and compared size-based measurements according to Response Evaluation Criteria in Solid Tumors (RECIST) with size- and density-based response evaluations according to the Choi criteria. PATIENTS AND METHODS: A total of 22 patients treated with sorafenib (800 mg/d) were retrospectively analyzed. Relative changes (in %) in the greatest diameter and density of defined neoplastic "target lesions" were determined 8 weeks and 1 year after start of therapy in relation to a pretherapeutic baseline investigation. Data were analyzed according to RECIST (ver. 1.0), and results were compared with the response assessment based on Choi. Median survival was determined for all subgroups according to Choi or RECIST at the 8-week and 1-year follow-up. RESULTS: Applying RECIST, 18 patients (82%) demonstrated stable disease (SD) 8 weeks after the start of targeted therapy, 3 patients (14%) partial response (PR), and 1 patient (4%) progressive disease (PD). Partial responders at 8 weeks had a median survival of 48 months. After 1 year, 59% of all patients still showed SD. Applying Choi, 15 patients (68%) showed PR 8 weeks after the start of therapy, 5 patients (23%) SD, and 2 patients (9%) PD. After 1 year, PR was still the predominant response group (64% of the patients). Partial responders after 8 weeks had a median survival of 18 months. CONCLUSION: Choi defined more patients as partial responders at early stages of therapy than RECIST, but this was not an effective selection for patients with prolonged median survival. Evaluation of a larger patient cohort will further clarify the role of combined size- and density-based follow-up strategies in targeted therapy of mRCC.

Left ventricular functional assessment in murine models of ischemic and dilated cardiomyopathy using [18 F]FDG-PET: comparison with cardiac MRI and monitoring erythropoietin therapy.

BACKGROUND: We performed an initial evaluation of non-invasive ECG-gated [18 F]FDG-positron emission tomography (FDG-PET) for serial measurements of left ventricular volumes and function in murine models of dilated (DCM) and ischemic cardiomyopathy (ICM), and then tested the effect of erythropoietin (EPO) treatment on DCM mice in a preliminary FDG-PET therapy monitoring study. METHODS: Mice developed DCM 8 weeks after injection with Coxsackievirus B3 (CVB3), whereas ICM was induced by ligation of the left anterior descending artery. LV volumes (EDV and ESV) and the ejection fraction (LVEF) of DCM, ICM and healthy control mice were measured by FDG-PET and compared with reference standard results obtained with 1.5 T magnetic resonance imaging (MRI). In the subsequent monitoring study, LVEF of DCM mice was evaluated by FDG-PET at baseline, and after 4 weeks of treatment, with EPO or saline. RESULTS: LV volumes and the LVEF as measured by FDG-PET correlated significantly with the MRI results. These correlations were higher in healthy and DCM mice than in ICM mice, in which LVEF measurements were somewhat compromised by absence of FDG uptake in the area of infarction. LV volumes (EDV and ESV) were systematically underestimated by FDG-PET, with net bias such that LVEF measurements in both models of heart disease exceeded by 15% to 20% results obtained by MRI. In our subsequent monitoring study of DCM mice, we found a significant decrease of LVEF in the EPO group, but not in the saline-treated mice. Moreover, LVEF in the EPO and saline mice significantly correlated with histological scores of fibrosis. CONCLUSIONS: LVEF estimated by ECG-gated FDG-PET significantly correlated with the reference standard MRI, most notably in healthy mice and mice with DCM. FDG-PET served for longitudinal monitoring of effects of EPO treatment in DCM mice.

Tc-99m sestamibi single photon emission computed tomography for guiding percutaneous coronary intervention in patients with multivessel disease: a comparison with quantitative coronary angiography and fractional flow reserve.

To evaluate the accuracy of myocardial perfusion SPECT (MPI) in the detection and allocation of vessel specific perfusion defects (PD) using standard distribution territories in a routine clinical procedure of patients with multivessel disease (MVD). Combined quantitative coronary angiography and fractional flow reserve (QCA/FFR) measurements were used as invasive reference standard. 216 vessels in 72 MVD patients (67 +/- 10 years, 28 female) were investigated using MPI and QCA. FFR of 93 vessels with intermediate stenoses was determined. MPI detected significant stenoses according to QCA/FFR findings with a sensitivity of 85%. However, vessel-based evaluation using standard myocardial distribution territories delivered a sensitivity of only 62% (28 MPI+ out of 45 (QCA/FFR)+ findings), with specificity, PPV and NPV of 90, 62 and 90%. 7/17 false positive and 7/17 false negative findings (41%) could be attributed to incorrect allocation of reversible PD to their respective coronary arteries. 6/17 (35%) perfusion territories were classified as false negative when additional fixed PD were present. MPI had reasonable sensitivity for the detection of significant coronary artery disease in patients with multivessel disease. However, sensitivity decreased markedly, when the significance of each individual stenosis was evaluated using standard myocardial supplying territories. In this setting, 41% of false negative and false positive MPI findings resulted from incorrect allocation of reversible perfusion defects to their determining supplying vessel.

In vivo imaging of macrophage activity in the coronary arteries using 68Ga-DOTATATE PET/CT: correlation with coronary calcium burden and risk factors.

UNLABELLED: We measured the uptake of the somatostatin receptor ligand (68)Ga-[1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid]-D-Phe(1),Tyr(3)-octreotate (DOTATATE) in the left anterior descending coronary artery (LAD) in association with calcified plaques (CPs) and cardiovascular risk factors. METHODS: Seventy consecutive tumor patients were examined by whole-body (68)Ga-DOTATATE contrast-enhanced PET/CT. Blood-pool-corrected standardized uptake value (target-to-background ratio) was measured in the LAD, and CT images were used to detect CP. Cardiovascular risk factors and history of prior cardiovascular events were recorded. RESULTS: (68)Ga-DOTATATE uptake was detectable in the LAD of all patients. Target-to-background ratio in the LAD correlated significantly with the presence of CP (R = 0.34; P < 0.01), prior vascular events (R = 0.26; P < 0.05), and male sex (R = 0.29; P < 0.05), whereas CP correlated with these parameters but also with age (R = 0.34; P < 0.01) and hypertension (R = 0.25; P < 0.05). CONCLUSION: In a series of oncologic patients, those with prior cardiovascular events and calcified atherosclerotic plaques showed significantly increased (68)Ga-DOTATATE uptake in the LAD, suggesting a potential role of this tracer for plaque imaging in the coronary arteries.

Myocardial perfusion imaging is feasible for infarct size quantification in mice using a clinical single-photon emission computed tomography system equipped with pinhole collimators.

INTRODUCTION: The aim of this study is to evaluate a non-invasive method for measuring myocardial perfusion defect size in mice using a clinical single-photon emission computed tomography system equipped with pinhole collimators (pinhole SPECT). MATERIALS AND METHODS: Thirty days after ligation of the left anterior descending coronary artery, 13 mice (C57BL/6J) were imaged following intravenous injection of 370 MBq [99mTc]sestamibi. Eight control mice without myocardial infarction were likewise investigated. Image quality optimization had been achieved by repeated scanning of a multiple point phantom, with varying zoom factors, number of projection angles, and pinhole diameter. Volumetric sampling was used to generate polar maps, in which intensity was normalized to that of a standard septal region of interest (ROI), which was set at 100%. Receiver operating characteristic analyses were performed to define an optimal threshold as compared to histologically measured defect sizes, which were considered as gold standard. RESULTS: A spatial resolution of 1.9 mm was achieved using a pinhole diameter of 0.5 mm, a zoom factor of 2, and 6 degrees projection angles. Histological results were best reproduced by a 60% threshold relative to the septal reference ROI. By applying this threshold, SPECT perfusion defect sizes revealed very high correlation to the histological results (R(2) = 0.867) with excellent intra- and interobserver reproducibility (intraclass correlation coefficients of 0.84 and 0.82). CONCLUSIONS: We achieved a spatial resolution of 1.9 mm in myocardial perfusion imaging in mice using a clinical SPECT system mounted with pinhole collimators. Compared to a histological gold standard, the infarct sizes were accurately estimated, indicating that this method shows promise to monitor experimental cardiac interventions in mice.