We investigated the ability of targeted immunomicelles to detect and assess macrophages in atherosclerotic plaque using MRI in vivo . There is a large clinical need for a noninvasive tool to assess atherosclerosis from a molecular and cellular standpoint. Macrophages play a central role in atherosclerosis and are associated with plaques vulnerable to rupture. Therefore, macrophage scavenger receptor (MSR) was chosen as a target for molecular MRI. MSR-targeted immunomicelles, micelles, and gadolinium–diethyltriaminepentaacetic acid (DTPA) were tested in ApoE−/− and WT mice by using in vivo MRI. Confocal laser-scanning microscopy colocalization, macrophage immunostaining and MRI correlation, competitive inhibition, and various other analyses were performed. In vivo MRI revealed that at 24 h postinjection, immunomicelles provided a 79% increase in signal intensity of atherosclerotic aortas in ApoE−/− mice compared with only 34% using untargeted micelles and no enhancement using gadolinium–DTPA. Confocal laser-scanning microscopy revealed colocalization between fluorescent immunomicelles and macrophages in plaques. There was a strong correlation between macrophage content in atherosclerotic plaques and the matched in vivo MRI results as measured by the percent normalized enhancement ratio. Monoclonal antibodies to MSR were able to significantly hinder immunomicelles from providing contrast enhancement of atherosclerotic vessels in vivo . Immunomicelles provided excellent validated in vivo enhancement of atherosclerotic plaques. The enhancement seen is related to the macrophage content of the atherosclerotic vessel areas imaged. Immunomicelles may aid in the detection of high macrophage content associated with plaques vulnerable to rupture.

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 ¹⁸F-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.

Echocardiography plays a key role in the diagnosis of infective endocarditis (IE) but can be inconclusive in patients in whom prosthetic valve endocarditis (PVE) is suspected. The incremental diagnostic value of ¹⁸F-FDG PET and radiolabeled leukocyte scintigraphy in IE patients has already been reported. The aim of this study was to compare the respective performance of ¹⁸F-FDG PET and leukocyte scintigraphy for the diagnosis of PVE in 39 patients. Methods: ¹⁸F-FDG PET and leukocyte scintigraphy were performed on 39 consecutive patients admitted because of clinically suspected PVE and inconclusive echocardiography results. The results of ¹⁸F-FDG PET and leukocyte scintigraphy were analyzed separately and retrospectively by experienced physicians masked to the results of the other imaging technique and to patient outcome. The final Duke–Li IE classification was made after a 3-mo follow-up. Results: Of the 39 patients, 14 were classified as having definite IE, 4 as having possible IE, and 21 as not having IE. The average interval between ¹⁸F-FDG PET and leukocyte scintigraphy was 7 ± 7 d. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 93%, 71%, 68%, 94%, and 80%, respectively, for ¹⁸F-FDG PET and 64%, 100%, 100%, 81%, and 86%, respectively, for leukocyte scintigraphy. Discrepancies between the results of ¹⁸F-FDG PET and leukocyte scintigraphy occurred in 12 patients (31%). In patients with definite IE, 5 had true-positive ¹⁸F-FDG PET results but false-negative leukocyte scintigraphy results. Of these 5 patients, 3 had nonpyogenic microorganism IE (Coxiella or Candida). Of patients for whom endocarditis had been excluded, 6 had true-negative leukocyte scintigraphy results but false-positive ¹⁸F-FDG PET results. These 6 patients had been imaged in the first 2 mo after the last cardiac surgery. The last patient with a discrepancy between ¹⁸F-FDG PET and leukocyte scintigraphy was classified as having possible endocarditis and had positive ¹⁸F-FDG PET results and negative leukocyte scintigraphy results. Conclusion: ¹⁸F-FDG PET offers high sensitivity for the detection of active infection in patients with suspected PVE and inconclusive echocardiography results. Leukocyte scintigraphy offers a higher specificity, however, than ¹⁸F-FDG PET for diagnosis of IE and should be considered in cases of inconclusive ¹⁸F-FDG PET findings or in the first 2 mo after cardiac surgery.

To prospectively determine whether early first-pass perfusion and delayed-enhancement magnetic resonance (MR) imaging sequences can enable differentiation of acute myocardial infarction (AMI) from myocarditis in patients with acute chest pain. All examinations were performed according to guidelines of the institutional board on medical ethics and clinical investigation and after informed patient consent was obtained. Fifty-five patients with a clinical presentation suggestive but not typical of AMI were examined. At final diagnosis, 31 patients had AMI and 24 had myocarditis. At-rest MR imaging was performed and included first-pass perfusion and delayed-enhancement sequences. Three independent observers read each image data set separately and then in consensus. The main abnormalities included first-pass perfusion defects and delayed highly enhancing areas. The numbers and distributions of involved segments and the transmural extents and the shapes of the highly enhancing areas were noted. For comparisons between the AMI and myocarditis patient groups, the chi2 test was used to assess the locations of the abnormalities and the Mann-Whitney U test was used to assess the numbers of involved segments. The final diagnoses were obtained with coronary angiography as the reference standard for the AMI group and on the basis of normal coronary angiographic findings and the spontaneous resolution of clinical symptoms and wall motion abnormalities for the myocarditis group. MR imaging patterns were significantly different between the two cardiac disease groups (P < .05). All the patients with AMI had a segmental early subendocardial defect, with corresponding segmental subendocardial or transmural delayed high enhancement in a predominantly anteroseptal or inferior vascular distribution in 28 patients. All patients with AMI had stenosis of at least the infarct-affected coronary artery. All but one of the patients with myocarditis had no early defect and focal or diffuse nonsegmental nonsubendocardial delayed enhancement predominantly in an inferolateral location. Use of combined early- and late-perfusion MR imaging sequences helps to distinguish AMI from myocarditis.