Volumetric 68Ga-DOTA-TATE PET/CT for assessment of whole-body tumor burden as a quantitative imaging biomarker in patients with metastatic gastroenteropancreatic neuroendocrine tumors.

BACKGROUND: A quantitative imaging biomarker is desirable to provide a comprehensive measure of whole-body tumor burden in patients with metastatic neuroendocrine tumors, and to standardize the evaluation of treatment-related changes. Therefore, we evaluated volumetric parameters for quantification of whole-body tumor burden from somatostatin receptor (SSR)-targeted PET/CT. METHODS: Thirty-two patients with metastastic grade1/grade 2 gastroenteropancreatic neuroendocrine tumors who underwent a 68Ga-DOTA-TATE PET/CT for staging of disease before initiation of peptide receptor radionuclide therapy were included in this retrospective cohort analysis. Volumetric parameters of tumor lesions, SSR-derived tumor volume (SSR-TV) and total lesion SSR (TL-SSR), were calculated for each patient using a computerized volumetric technique with a 40% SUVmax cut-off, and compared with serum chromogranin A (CgA) levels. Progression-free survival (PFS) was determined in relation to volumetric parameters. In a subgroup of 18 patients, the feasibility of volumetric parameters for treatment monitoring was evaluated. RESULTS: Mean SSR-TV was 178±214 cm3 (range, 9-797 cm3), whereas mean TL-SSR was 4096±5191 cm3 (range, 61-19,203 cm3). Baseline CgA levels were associated with whole-body tumor burden (SSR-TV, r=0.57, P=0.0008; and TL-SSR, r=0.43, P=0.01, respectively). PFS was shorter in patients with high SSR-TV and high TL-SSR (HR 5.16, 95% CI, 1.61-29.67), P=0.009), and SSR-TV (P=0.0067) and TL-SSR (P=0.0215) emerged as the sole predictors of progression in regression analysis. Changes in CgA did not correctly identify treatment response (P=0.25). CONCLUSIONS: SSR-derived volumetric parameters provide a quantitative imaging biomarker for whole-body tumor burden, and may hold potential as a clear-cut measure for assessment of treatment response.

Assessment of γ-H2AX and 53BP1 Foci in Peripheral Blood Lymphocytes to Predict Subclinical Hematotoxicity and Response in Somatostatin Receptor-Targeted Radionuclide Therapy for Advanced Gastroenteropancreatic Neuroendocrine Tumors.

BACKGROUND: We aimed to characterize γ-H2AX and 53BP1 foci formation in patients receiving somatostatin receptor-targeted radioligand therapy, and explored its role for predicting treatment-related hematotoxicity, and treatment response. METHODS: A prospective analysis of double-strand break (DSB) markers was performed in 21 patients with advanced gastroenteropancreatic neuroendocrine tumors. γ-H2AX and 53BP1 foci formation were evaluated in peripheral blood lymphocytes (PBLs) at baseline, +1 h and +24 h after administration of 7.4 GBq (177Lu)Lu-DOTA-TATE. Hematotoxicity was evaluated using standard hematology. Therapy response was assessed using (68Ga)Ga-DOTA-TATE PET/CT before enrollment and after 2 cycles of PRRT according to the volumetric modification of RECIST 1.1. RESULTS: DSB marker kinetics were heterogeneous among patients. Subclinical hematotoxicity was associated with γ-H2AX and 53BP1 foci formation (e.g., change in platelet count vs change in γ-H2AX+ cells between baseline and +1 h (r = -0.6080; p = 0.0045). Patients showing early development of new metastases had less γ-H2AX (p = 0.0125) and less 53BP1 foci per cell at +1 h (p = 0.0289), and demonstrated a distinct kinetic pattern with an absence of DSB marker decrease at +24 h (γ-H2AX: p = 0.0025; 53BP1: p = 0.0008). CONCLUSIONS: Assessment of γ-H2AX and 53BP1 foci formation in PBLs of patients receiving radioligand therapy may hold promise for predicting subclinical hematotoxicity and early treatment response.

Clinical quantitative cardiac imaging for the assessment of myocardial ischaemia.

Cardiac imaging has a pivotal role in the prevention, diagnosis and treatment of ischaemic heart disease. SPECT is most commonly used for clinical myocardial perfusion imaging, whereas PET is the clinical reference standard for the quantification of myocardial perfusion. MRI does not involve exposure to ionizing radiation, similar to echocardiography, which can be performed at the bedside. CT perfusion imaging is not frequently used but CT offers coronary angiography data, and invasive catheter-based methods can measure coronary flow and pressure. Technical improvements to the quantification of pathophysiological parameters of myocardial ischaemia can be achieved. Clinical consensus recommendations on the appropriateness of each technique were derived following a European quantitative cardiac imaging meeting and using a real-time Delphi process. SPECT using new detectors allows the quantification of myocardial blood flow and is now also suited to patients with a high BMI. PET is well suited to patients with multivessel disease to confirm or exclude balanced ischaemia. MRI allows the evaluation of patients with complex disease who would benefit from imaging of function and fibrosis in addition to perfusion. Echocardiography remains the preferred technique for assessing ischaemia in bedside situations, whereas CT has the greatest value for combined quantification of stenosis and characterization of atherosclerosis in relation to myocardial ischaemia. In patients with a high probability of needing invasive treatment, invasive coronary flow and pressure measurement is well suited to guide treatment decisions. In this Consensus Statement, we summarize the strengths and weaknesses as well as the future technological potential of each imaging modality.

[Policy paper nuclear cardiology - update 2018 - Current status of clinical practice]. / Positionspapier Nuklearkardiologie ­ Update 2018.

The joint position paper of the working community "Cardiovascular Nuclear Medicine" of the German Society of Nuclear Medicine (DGN) and the working group "Nuclear Cardiology Diagnostics" of the German Cardiac Society (DKG) updates the former 2009 paper. It is the purpose of this paper to provide an overview about the application fields, the state-of-the-art and the current value of nuclear cardiology imaging. The topics covered are chronic coronary artery disease, including viability imaging, furthermore cardiomyopathies, infective endocarditis, cardiac sarcoidosis and amyloidosis.

Quantitation of Perfused Lung Volume Using Hybrid SPECT/CT Allows Refining the Assessment of Lung Perfusion and Estimating Disease Extent in Chronic Thromboembolic Pulmonary Hypertension.

BACKGROUND: We evaluated the feasibility of perfusion SPECT/CT for providing quantitative data for estimation of perfusion defect extent in chronic thromboembolic pulmonary hypertension (CTEPH). METHODS: Thirty patients with CTEPH underwent Tc-human serum albumin lung perfusion SPECT/CT. Perfusion defects were quantified using 3 different methods: (1) visual, semiquantitative scoring of perfusion defect extent in each lung segment, (2) threshold-based segmentation of perfused lung volumes, and (3) threshold-based segmentation of perfused lung volumes divided by segmented lung volumes at CT (perfusion index). Imaging findings were correlated with right-sided heart catheterization results and N-terminal pro-B-type natriuretic peptide. Receiver operating characteristic analysis was performed to identify SPECT thresholds for mean pulmonary arterial pressure (PAPm) greater than 50 mm Hg. RESULTS: Assessment of lung perfusion provided similar results using all 3 methods. The perfusion defect score correlated with PAPm (rs = 0.60, P = 0.0005) and was associated with serum levels of N-terminal pro-B-type natriuretic peptide (rs = 0.37, P = 0.04). Perfused lung volume (40% threshold, rs = -0.48, P = 0.007) and perfusion index (40% threshold, rs = -0.50, P = 0.005) decreased as PAPm increased. Receiver operating characteristic analysis showed that perfusion defect score (sensitivity, 88%; specificity, 77%; area under the curve [AUC] = 0.89, P = 0.001), perfused lung volume (sensitivity, 88%; specificity, 64%; AUC = 0.80, P = 0.01), and perfusion index (sensitivity, 88%; specificity, 64%; AUC = 0.82, P = 0.009) could identify patients with PAPm of greater than 50 mm Hg. CONCLUSIONS: Quantitative analysis of perfusion defects at SPECT is feasible, provides a measure of disease severity, and correlates with established clinical parameters. Quantitation of perfusion SPECT may refine the diagnostic approach in CTEPH providing a quantitative imaging biomarker, for example, for therapy monitoring.

Initial Experience with Volumetric 68Ga-PSMA I&T PET/CT for Assessment of Whole-Body Tumor Burden as a Quantitative Imaging Biomarker in Patients with Prostate Cancer.

A quantitative imaging biomarker is desirable to provide a comprehensive measure of whole-body tumor burden in patients with metastatic prostate cancer, and to standardize the evaluation of treatment-related changes. Therefore, we evaluated whether prostate-specific membrane antigen (PSMA) ligand PET/CT may be applied to provide PSMA-derived volumetric parameters for quantification of whole-body tumor burden. Methods: One hundred one patients who underwent 68Ga-PSMA I&T PET/CT because of increasing prostate-specific antigen (PSA) levels after radical prostatectomy were included in this retrospective analysis. Tracer uptake was quantified using SUVs. Volumetric parameters, that is, PSMA-derived tumor volume (PSMA-TV) and total lesion PSMA (TL-PSMA), were calculated for each patient using a 3-dimensional segmentation and computerized volumetry technique and compared with serum PSA levels. In a group of 10 patients, volumetric parameters were applied for treatment monitoring. Results: Volumetric parameters, that is, whole-body PSMA-TV and whole-body TL-PSMA, demonstrated a statistically significant correlation with PSA levels (P < 0.0001) as a surrogate marker of tumor burden, whereas SUVmax (P = 0.22) or SUVmean (P = 0.45) did not. Treatment response and treatment failure were paralleled by concordant changes in both whole-body PSMA-TV and whole-body TL-PSMA (P = 0.02), whereas neither the change in SUVmax (P = 1.0) nor the change in SUVmean (P = 1.0) concordantly paralleled changes in PSA levels. Conclusion: PSMA-derived volumetric parameters provide a quantitative imaging biomarker for whole-body tumor burden, capable of standardizing quantitative changes in PET imaging of patients with metastatic prostate cancer and of facilitating therapy monitoring.

Expert System for Bone Scan Interpretation Improves Progression Assessment in Bone Metastatic Prostate Cancer.

INTRODUCTION: The bone scan index (BSI) was introduced as a quantitative tool for tumor involvement in bone of patients with metastatic prostate cancer (mPCa). The computer-aided diagnosis device for BSI analysis EXINIboneBSI seems to represent technical progress for the quantitative assessment of bone involvement. But it is not yet clear if the automated BSI (aBSI) could contribute to improved evaluation of progression in patients under antiandrogens or chemotherapy in contrast to the visual interpretation and/or conventional biomarkers such as the prostate-specific antigen (PSA). METHODS: In 49 mPCa patients, bone scans were performed initially and during different therapy courses. Scans were evaluated visually and by the artificial-neural-network-based expert system EXINIboneBSI. Progression of metastatic bone involvement was defined according to the Prostate Cancer Clinical Trials Working Group 2 (PCWG2) criteria in the visual interpretation. The computer-assisted interpretation was based on different cutoff values in relative changes of the aBSI. Additionally, assessments according to bone scanning were compared to changes in the PSA value as a potential surrogate for treatment response. RESULTS: Using a sensitive cutoff value (5% or 10%) for the relative aBSI increase led to significantly increased progression determination compared to the visual interpretation of bone scans (49% and 43% vs. 27%, p < 0.001). In 63% of the cases PSA and BSI changes matched, whereas in 18% progression was only indicated by the aBSI. A relative cutoff of 5% for the aBSI decrease could reclassify 47 serial scan pairs which were visually interpreted as stable into 22 progressive and 25 remissive scans. CONCLUSION: Distinct thresholds of the relative aBSI could help to better assess disease progression in mPCa patients. Manual corrections of the BSI values are not required in most cases. The aBSI could serve as a useful additional parameter for therapy monitoring in mPCa patients in the future.

68Ga-PSMA I&T PET/CT for assessment of prostate cancer: evaluation of image quality after forced diuresis and delayed imaging.

OBJECTIVE: Urinary radiotracer excretion of 68Ga-Labelled prostate-specific membrane antigen (PSMA) ligands may complicate the assessment of the prostate region and differentiation of lymph nodes from ureteral activity. The aim of this study was to assess the value of delayed imaging after forced diuresis. MATERIALS AND METHODS: Sixty-six patients underwent 68Ga-PSMA I&T PET/CT for evaluation of prostate cancer at 60 min post-injection. In subgroups of patients, this was amended by delayed imaging after 180 min post-injection, preceded by furosemide and oral hydration early, at the time of tracer injection, or delayed, at 100 min post-injection. Urinary tracer activity within the bladder and focal ureteral activity was analyzed. RESULTS: After forced diuresis, linear and focal visualization of ureters was significantly reduced. After delayed furosemide, mean and peak bladder activity decreased (p < 0.001), and image quality of the prostate region improved on delayed images (p < 0.001). Early furosemide co-injection with tracer resulted in increased mean and peak bladder activity (p < 0.001) and in deteriorated image quality of the prostate region on delayed images (p = 0.008). CONCLUSION: Ga-PSMA I&T PET/CT delayed imaging after forced diuresis can improve the assessment of prostate region and pelvic lymph nodes by removing excreted tracer from the lower urinary tract. KEY POINTS: • Forced diuresis can improve image quality in 68 Ga-PSMA I&T. • After forced diuresis, linear and focal visualization of ureters was reduced. • Timing of diuresis relative to 68 Ga-PSMA I&T injection is important. • Early furosemide co-injection with tracer resulted in deteriorated image quality on delayed images. • After delayed furosemide, image quality improved on delayed images.

Assessment of bone marrow inflammation in patients with myelofibrosis: an 18F-fluorodeoxyglucose PET/CT study.

PURPOSE: Myelofibrosis is a haematopoietic stem cell neoplasm characterized by bone marrow inflammation, reactive marrow fibrosis and extramedullary haematopoiesis. The aim of this study was to determine if (18)F-FDG PET/CT can be used to noninvasively visualize and quantify the extent and activity of bone marrow involvement. METHODS: In 30 patients, the biodistribution of (18)F-FDG was analysed by measuring the standardized uptake value in the bone marrow compartment and spleen. Imaging findings were compared with laboratory, cytogenetic and histopathological data. RESULTS: Retention of (18)F-FDG was observed in bone marrow and spleen. Bone marrow involvement varied, ranging from mildly increased uptake in the central skeleton to extensive uptake in most parts of the skeleton. The extent of bone marrow involvement decreased over time from initial diagnosis (r s = -0.43, p = 0.019). Metabolic activity of the bone marrow decreased as the histopathological grade of fibrosis increased (r s = -0.37, p = 0.04). There was a significant positive correlation between the metabolic activity of the bone marrow and that of the spleen (p = 0.04). CONCLUSION: (18)F-FDG PET/CT is as a promising technique for the quantitation of bone marrow inflammation in myelofibrosis. Our data indicate that the intensity of bone marrow (18)F-FDG uptake decreases as bone marrow fibrosis increases. Further evaluation in prospective studies is required to determine the potential clinical impact and prognostic significance of PET.

Anatomic versus physiologic assessment of coronary artery disease. Role of coronary flow reserve, fractional flow reserve, and positron emission tomography imaging in revascularization decision-making.

Angiographic severity of coronary artery stenosis has historically been the primary guide to revascularization or medical management of coronary artery disease. However, physiologic severity defined by coronary pressure and/or flow has resurged into clinical prominence as a potential, fundamental change from anatomically to physiologically guided management. This review addresses clinical coronary physiology-pressure and flow-as clinical tools for treating patients. We clarify the basic concepts that hold true for whatever technology measures coronary physiology directly and reliably, here focusing on positron emission tomography and its interplay with intracoronary measurements.

Assessment of cardiac autonomic neuronal function using PET imaging.

The autonomic nervous system is the primary extrinsic control of cardiac performance, and altered autonomic activity has been recognized as an important factor in the progression of various cardiac pathologies. Molecular imaging techniques have been developed for global and regional interrogation of pre- and postsynaptic targets of the cardiac autonomic nervous system. Building on established work with the guanethidine analogue ¹²³I-metaiodobenzylguanidine (MIBG) for single-photon emission tomography (SPECT), development of radiotracers and protocols for positron emission tomography (PET) investigation of autonomic signaling has expanded. PET is limited in availability and requires specialized centers for radiosynthesis and interpretation, but the higher resolution allows for improved regional analysis and kinetic modeling provides more true quantification than is possible with SPECT. A wider array of radiolabeled catecholamines, analogues of catecholamines, and receptor ligands have been characterized and evaluated. Sympathetic neuronal PET tracers have shown promise in the identification of several cardiac pathologies. In particular, recent studies have elucidated a mechanistic role for heterogeneous sympathetic innervation in the development of lethal ventricular arrhythmias. Evaluation of cardiomyocyte adrenergic receptor expression and the parasympathetic nervous system has been slower to develop, with clinical studies beginning to emerge. This review summarizes the clinical and the experimental PET tracers currently available for autonomic imaging and discusses their application in health and cardiovascular disease, with particular emphasis on the major findings of the last decade.

Transient ischemic dilation ratio in 82Rb PET myocardial perfusion imaging: normal values and significance as a diagnostic and prognostic marker.

UNLABELLED: In myocardial perfusion SPECT, transient ischemic dilation ratio (TID) is a well-established marker of severe ischemia and adverse outcome. However, its role in the setting of (82)Rb PET is less well defined. METHODS: We analyzed 265 subjects who underwent clinical rest-dipyridamole (82)Rb PET/CT. Sixty-two subjects without a prior history of cardiac disease and with a normal myocardial perfusion study had either a low or a very low pretest likelihood of coronary artery disease or negative CT angiography. These subjects were used to establish a reference range of TID. In the remaining 203 patients with an intermediate or high pretest likelihood, subgroups with normal and abnormal TID were established and compared with respect to clinical variables, perfusion defect scores, left ventricular function, and absolute myocardial flow reserve. Follow-up was obtained for 969 ± 328 d to determine mortality by review of the social security death index. RESULTS: In the reference group, TID ratio was 0.98 ± 0.06. Accordingly, a threshold for abnormal TID was set at greater than 1.13 (0.98 + 2.5 SDs). In the study group, 19 of 203 patients (9%) had an elevated TID ratio. Significant differences between subgroups with normal and abnormal TID ratio were observed for ejection fraction reserve (5.0 ± 6.4 vs. 1.8 ± 7.9; P < 0.05), difference between end-systolic volume (ESV) at rest and stress (ΔESV[stress-rest]; 1.8 ± 7.4 vs. 12.3 ± 13.0 mL; P < 0.0001), difference between end-diastolic volume (EDV) at rest and stress (ΔEDV[stress-rest]; 10.8 ± 11.5 vs. 23.8 ± 14.6 mL; P < 0.0001), summed rest score (1.8 ± 3.8 vs. 3.8 ± 7.6; P < 0.05), summed stress score (3.0 ± 5.4 vs. 7.5 ± 9.8; P < 0.002), summed difference score (1.3 ± 2.6 vs. 3.7 ± 5.3; P < 0.02), and global myocardial flow reserve (2.1 ± 0.8 vs. 1.7 ± 0.6; P < 0.02). Additionally, TID-positive patients had a significantly lower overall survival probability (P < 0.05). In a subgroup analysis of patients without regional perfusion abnormalities, TID-positive patients' overall survival probability was significantly smaller (P < 0.03), and TID was an independent predictor (exponentiation of the B coefficients [Exp(b)] = 6.22; P < 0.009) together with an ejection fraction below 45% (Exp[b] = 6.16; P < 0.002). CONCLUSION: The present study suggests a reference range of TID for (82)Rb PET myocardial perfusion imaging that is in the range of previously established values for SPECT. Abnormal TID in (82)Rb PET is associated with more extensive left ventricular dysfunction, ischemic compromise, and reduced global flow reserve. Preliminary outcome analysis suggests that TID-positive subjects have a lower overall survival probability.

PET/CT assessment of symptomatic individuals with obstructive and nonobstructive hypertrophic cardiomyopathy.

UNLABELLED: Patients with obstructive hypertrophic cardiomyopathy (HCM) exhibit elevated left ventricular outflow tract gradients (LVOTGs) and appear to have a worse prognosis than those with nonobstructive HCM. The aim of this study was to evaluate whether patients with obstruction, compared with nonobstructive HCM, demonstrate significant differences in PET parameters of microvascular function. METHODS: PET was performed in 33 symptomatic HCM patients at rest and during dipyridamole stress (peak) for the assessment of regional myocardial perfusion (rMP), left ventricular ejection fraction (LVEF), myocardial blood flow (MBF), and myocardial flow reserve (MFR). Myocardial wall thickness and LVOTG were measured with an echocardiogram. Patients were divided into the following 3 groups: nonobstructive (LVOTG < 30 mm Hg at rest and after provocation test with amyl nitrite), obstructive (LVOTG ≥ 30 mm Hg at rest and with provocation), and latent HCM (LVOTG < 30 at rest but ≥ 30 mm Hg with provocation). RESULTS: Eleven patients were classified as nonobstructive (group 1), 12 as obstructive (group 2), and 10 as latent HCM (group 3). Except for age (42 ± 18 y for group 1, 58 ± 7 y for group 2, and 58 ± 12 y for group 3; P = 0.01), all 3 groups had similar baseline characteristics, including maximal wall thickness (2.3 ± 0.5 cm for group 1, 2.2 ± 0.4 cm for group 2, and 2.1 ± 0.7 cm for group 3; P = 0.7). During peak flow, most patients in groups 1 and 2, but fewer in group 3, exhibited rMP defects (73% for group 1, 100% for group 2, and 40% for group 3; P = 0.007) and a drop in LVEF (73% for group 1, 92% for group 2, and 50% for group 3; P = 0.09). Peak MBF (1.58 ± 0.49 mL/min/g for group 1, 1.72 ± 0.46 mL/min/g for group 2, and 1.97 ± 0.32 mL/min/g for group 3; P = 0.14) and MFR (1.62 ± 0.57 for group 1, 1.90 ± 0.31 for group 2, and 2.27 ± 0.51 for group 3; P = 0.01) were lower in the nonobstructive and higher in the latent HCM group. LVOTGs demonstrated no significant correlation with any flow dynamics. In a multivariate regression analysis, maximal wall thickness was the only significant predictor for reduced peak MBF (ß = -0.45, P = 0.003) and MFR (ß = -0.63, P = 0.0001). CONCLUSION: Maximal wall thickness was identified as the strongest predictor of impaired dipyridamole-induced hyperemia and flow reserve in our study, whereas outflow tract obstruction was not an independent determinant.

[Position paper nuclear cardiology: update 2008]. / Positionsbericht Nuklearkardiologie Update 2008: Aktueller Stand der szintigraphischen Methodik.

Nuclear cardiology is well established in clinical diagnostic algorithms for many years. This is an update 2008 of the first common position paper of the German Association of Nuclear Medicine and the German Association of Cardiology, Heart and Circulation Research published in 2001 aiming at an overview of state-of-the-art scintigraphic methods.

Rubidium-82 PET-CT for quantitative assessment of myocardial blood flow: validation in a canine model of coronary artery stenosis.

PURPOSE: Absolute quantification of myocardial blood flow expands the diagnostic potential of PET for assessment of coronary artery disease. (82)Rb has significantly contributed to increasing utilization of PET; however, clinical studies are still mostly analysed qualitatively. The aim of this study was to reevaluate the feasibility of (82)Rb for flow quantification, using hybrid PET-CT in an animal model of coronary stenosis. METHODS: Nine dogs were prepared with experimental coronary artery stenosis. Dynamic PET was performed for 8 min after (82)Rb(1480-1850 MBq) injection during adenosine-induced vasodilation. Microspheres were injected simultaneously for reference flow measurements. CT angiography was used to determine the myocardial regions related to the stenotic vessel. Two methods for flow calculation were employed: a two-compartment model including a spill-over term, and a simplified retention index. RESULTS: The two-compartment model data were in good agreement with microsphere flow (y = 0.84x + 0.20; r = 0.92, p<0.0001), although there was variability in the physiological flow range <3 ml/g per minute (y = 0.54x + 0.53; r = 0.53, p = 0.042). Results from the retention index also correlated well with microsphere flow (y = 0.47x + 0.52; r = 0.75, p = 0.0004). Error increased with higher flow, but the correlation was good in the physiological range (y = 0.62x + 0.29; r = 0.84, p = 0.0001). CONCLUSION: Using current state-of-the-art PET-CT systems, quantification of myocardial blood flow is feasible with (82)Rb. A simplified approach based on tracer retention is practicable in the physiological flow range. These results encourage further testing of the robustness and usefulness in the clinical context of cardiac hybrid imaging.

[Myocardial perfusion scintigraphy. Exact and cost-effective coronary disease imaging--secondary publication]. / Myokardieskintigrafi. Praecis og omkostningseffektiv billeddiagnostik ved koronarsygdom--sekundaerpublikation.

Mortality rates due to coronary arterial disease (CAD) have declined as result of improved prevention, diagnosis and management, but CAD remains the leading cause of death. Myocardial perfusion scintigraphy (MPS) provides a cost-effective tool for early detection of CAD in symptomatic individuals and can stratify patients according to risk of cardiac events. MPS also provides valuable information to assist clinical decision-making. A large body of evidence supports the current applications of MPS, which has become integral to several guidelines for clinical practice.

Lowering radiation dose for integrated assessment of coronary morphology and physiology: first experience with step-and-shoot CT angiography in a rubidium 82 PET-CT protocol.

BACKGROUND: Reduction of radiation exposure from computed tomography coronary angiography (CTA) will be a key factor for more liberal use in cardiac hybrid positron emission tomography (PET)-computed tomography (CT). We report our initial experience with a new algorithm for low-dose CTA based on a prospectively gated step-and-shoot technique. This limits acquisition to the diastolic phase and minimizes exposure time versus the previous standard of retrospectively gated helical acquisitions. METHODS AND RESULTS: In 15 consecutive patients referred for integrated functional and morphologic workup by rubidium 82 perfusion PET-CTA, step-and-shoot CTA (SnapShot Pulse; GE Medical Systems) (120 kV, 600-800 mA) was acquired on a 64-slice GE Discovery Rx VCT PET-CT scanner and compared with a group of patients with conventional helical CTA (120 kV, with modulation of the milliampere level) who were matched with regard to clinical variables. Effective dose was estimated from dose-length product. The American Heart Association 15-segment coronary tree model was used to determine study interpretability. Potential for fusion with Rb-82 perfusion PET was tested by use of commercial software. In addition, direct dose measurements were conducted by use of an anthropomorphic phantom for more accurate dosimetry. The dose-length product-derived effective patient dose for step-and-shoot and helical CTA was 5.5 +/- 0.1 mSv versus 20.5 +/- 3.5 mSv (P < .0001). The mean number of evaluable segments per patient for the best phase of helical CTA was 12.5 +/- 2.8 (83.3% +/- 18.7%) versus 13.3 +/- 2.2 (88.7% +/- 14.7%) (P = not significant vs helical) for step-and-shoot CTA. Review of multiple phases increased the number for helical CTA to 13.7 +/- 1.7 (91.3% +/- 11.3%; P = not significant vs step-and-shoot CTA, for which this was not an option). Semiautomated fusion with corresponding PET was feasible for all studies. Phantom data confirm effective doses of 5.4 mSv for step-and-shoot CTA and 19.6 mSv for helical acquisition. CONCLUSIONS: Low-dose prospectively gated CTA reduces radiation exposure by nearly 70% versus the previous standard of helical acquisition, without significant loss in interpretability and integrative potential with Rb-82 perfusion PET. This represents a step toward a broader, routine integration of CTA and perfusion PET for assessment of coronary morphology and physiology by cardiac PET-CT.

Assessment of alphavbeta3 integrin expression after myocardial infarction by positron emission tomography.

AIMS: The purpose of this study was to determine the feasibility of a new positron emission tomography (PET) imaging approach using an (18)F-labelled alpha(v)beta(3) integrin antagonist ((18)F-Galacto-RGD) to monitor the integrin expression after myocardial infarction. METHODS AND RESULTS: Male Wister rats were subjected to 20 min transient left coronary artery occlusion followed by reperfusion. Autoradiographic analysis and in vivo PET imaging were used to determine myocardial (18)F-Galacto-RGD uptake at different time points following reperfusion. RESULTS: PET imaging and autoradiography demonstrated no significant focal myocardial (18)F-Galacto-RGD uptake in non-operated control rats and at day 1 after reperfusion. However, focal accumulation in the infarct area started at day 3 (uptake ratio = 1.91 +/- 0.22 vs. remote myocardium), peaked between 1 (3.43 +/- 0.57) and 3 weeks (3.43 +/- 0.95), and decreased to 1.96 +/- 0.40 at 6 months after reperfusion. Pretreatment with alpha(v)beta(3) integrin antagonist c(-RGDfV-) significantly decreased tracer uptake, indicating the specificity of tracer uptake. The time course of focal tracer uptake paralleled vascular density as measured by CD31 immunohistochemical analysis. CONCLUSION: Regional (18)F-Galacto-RGD accumulation suggests up-regulation of alpha(v)beta(3) integrin expression after myocardial infarction, which peaks between 1 and 3 weeks and remains detectable until 6 months after reperfusion. This new PET tracer is promising for the monitoring of myocardial repair processes.

Clinical value, cost-effectiveness, and safety of myocardial perfusion scintigraphy: a position statement.

Mortality rates due to coronary artery disease (CAD) have declined in recent years as result of improved prevention, diagnosis, and management. Nonetheless, CAD remains the leading cause of death worldwide with most casualties expected to occur in developing nations. Myocardial perfusion scintigraphy (MPS) provides a highly cost-effective tool for the early detection of obstructive CAD in symptomatic individuals and contributes substantially to stratification of patients according to their risk of cardiac death or nonfatal myocardial infarction. MPS also provides valuable information that assists clinical decision-making with regard to medical treatment and intervention. A large body of evidence supports the current applications of MPS, which has become integral to several guidelines for clinical practice.

Assessment of cardiac sympathetic neuronal function using PET imaging.

The autonomic nervous system plays a key role for regulation of cardiac performance, and the importance of alterations of innervation in the pathophysiology of various heart diseases has been increasingly emphasized. Nuclear imaging techniques have been established that allow for global and regional investigation of the myocardial nervous system. The guanethidine analog iodine 123 metaiodobenzylguanidine (MIBG) has been introduced for scintigraphic mapping of presynaptic sympathetic innervation and is available today for imaging on a broad clinical basis. Not much later than MIBG, positron emission tomography (PET) has also been established for characterizing the cardiac autonomic nervous system. Although PET is methodologically demanding and less widely available, it provides substantial advantages. High spatial and temporal resolution along with routinely available attenuation correction allows for detailed definition of tracer kinetics and makes noninvasive absolute quantification a reality. Furthermore, a series of different radiolabeled catecholamines, catecholamine analogs, and receptor ligands are available. Those are often more physiologic than MIBG and well understood with regard to their tracer physiologic properties. PET imaging of sympathetic neuronal function has been successfully applied to gain mechanistic insights into myocardial biology and pathology. Available tracers allow dissection of processes of presynaptic and postsynaptic innervation contributing to cardiovascular disease. This review summarizes characteristics of currently available PET tracers for cardiac neuroimaging along with the major findings derived from their application in health and disease.