Head-to-head comparison of the diagnostic performances of Rubidium-PET and SPECT with CZT camera for the detection of myocardial ischemia in a population of women and overweight individuals.

BACKGROUND: The aim of this study was to compare the diagnostic performances for the detection of myocardial ischemia of 82-Rb-PET-MPS and 99m-Tc-SPECT-MPS in overweight individuals and women. METHODS AND RESULTS: Men with BMI ≥ 25 and women referred for MPS were considered for inclusion. All individuals underwent 99m-Tc-SPECT-MPS with CZT cameras and 82-Rb-PET-MPS in 3D-mode. Individuals with at least one positive MPS were referred for coronary angiography (CA) with FFR measurements. A criterion for positivity was a composite endpoint including significant stenosis on CA or, in the absence of CA, the occurrence of acute coronary event during the following year. 313 patients (46% women) with mean BMI of 31.8 ± 6.5 were included. Sensitivity for the detection of myocardial ischemia was higher with 82-Rb-PET-MPS compared with 99m-Tc-SPECT-MPS (85% vs. 57%, P < .05); specificity was equally high with both imaging techniques (93% vs. 94%, P > .05). 82-Rb-PET allowed for a more accurate detection of patients with a high-risk coronary artery disease (HR-CAD) than 99m-Tc-SPECT-MPS (AUC = 0.86 vs. 0.75, respectively; P = .04). CONCLUSIONS: In women and overweight individuals, 82-Rb-PET-MPS provides higher sensitivity for the detection of myocardial ischemia than 99m-Tc-SPECT-MPS thanks to a better image quality and an improved detection of HR-CAD.

Detection of Apoptotic Cells in a Rabbit Model with Atherosclerosis-Like Lesions Using the Positron Emission Tomography Radiotracer [18F]ML-10.

[18F]ML-10 (2-(5-fluoro-pentyl)-2-methylmalonic acid) is a positron emission tomography (PET) radiotracer that accumulates in cells presenting apoptosis-specific membrane alterations. The aim of this study was to test whether [18F]ML-10 allows for the detection of apoptotic cells located in atherosclerotic plaques in rabbits. Atherosclerotic plaques were induced in the aortas of five rabbits, and five additional rabbits were used as controls. Activity in the aortas was quantified in vivo and ex vivo. The localization of [18F]ML-10 to the aortic wall was identified by autoradiography. Average target to background ratios measured in vivo by PET were higher in the aortas of atherosclerotic rabbits compared with those of control rabbits (2.00 ± 0.52 vs 1.22 ± 0.30; p < .05). Differences in [18F]ML-10 uptake between atherosclerotic and control aortas were confirmed ex vivo by PET and gamma counting (23.9 ± 11.2 vs 1.1 ± 2.4 counts/pixel; p <.05; 3.6 ± 2.0 vs 0.05 ± 0.05 % of injected activity/g; p < .05, respectively). Strong correlation was observed between the accumulation of [18F]ML-10 in aortic segments as detected by autoradiography and the number of apoptotic cells on corresponding histologic sections (r2 = .75; p < .05). In this study, we found that atherosclerotic plaques rich in apoptotic cells can be detected with [18F]ML-10 and PET.

Variability and uncertainty of 18F-FDG PET imaging protocols for assessing inflammation in atherosclerosis: suggestions for improvement.

UNLABELLED: PET with (18)F-FDG shows promise for the evaluation of metabolic activities in atherosclerotic plaques. Although recommendations regarding the acquisition and measurement protocols to be used for (18)F-FDG PET imaging of atherosclerosis inflammation have been published, there is no consensus regarding the most appropriate protocols, and the image reconstruction approach has been especially overlooked. Given the small size of the targeted lesions, the reconstruction and measurement methods might strongly affect the results. We determined the differences in results due to the protocol variability and identified means of increasing the measurement reliability. METHODS: An extensive literature search was performed to characterize the variability in atherosclerosis imaging and quantification protocols. Highly realistic simulations of atherosclerotic carotid lesions based on real patient data were designed to determine how the acquisition and processing protocol parameters affected the measured values. RESULTS: In 49 articles, we identified 53 different acquisition protocols, 51 reconstruction protocols, and 46 quantification methods to characterize atherosclerotic lesions from (18)F-FDG PET images. The most important parameters affecting the measurement accuracy were the number of iterations used for reconstruction and the postfiltering applied to the reconstructed images, which could together make the measured standardized uptake values (SUVs) vary by a factor greater than 3. Image sampling, acquisition duration, and metrics used for the measurements also affected the results to a lesser extent (SUV varying by a factor of 1.3 at most). For an acceptable SUV variability, the lowest bias in SUV was observed using an 8-min acquisition per bed position; ordered-subset expectation maximization reconstruction with at least 120 maximum likelihood expectation maximization equivalent iterations, including a point spread function model using a 1 mm(3) voxel size; and no postfiltering. Because of the partial-volume effect, measurement bias remained greater than 60%. The use and limitations of the target-to-blood activity ratio metrics are also presented and discussed. CONCLUSION: (18)F-FDG PET protocol harmonization is needed in atherosclerosis imaging. Optimized protocols can significantly reduce the measurement errors in wall activity estimates, but PET systems with higher spatial resolution and advanced partial-volume corrections will be required to accurately assess plaque inflammation from (18)F-FDG PET.

Clinical activity of lenalidomide in visceral human immunodeficiency virus-related Kaposi sarcoma.

IMPORTANCE: Curative treatment of aggressive Kaposi sarcoma (KS) with conventional chemotherapy in human immunodeficiency virus (HIV)-infected patients remains difficult. The administration of thalidomide, an immunomodulatory drug with antiangiogenic effects, is limited by its toxicity. This engenders interest in evaluating thalidomide analogues such as lenalidomide with better toxicity profiles. To our knowledge, we describe for the first time a patient with visceral KS successfully treated with lenalidomide. OBSERVATIONS: A man with advanced visceral HIV-related KS progressing after 11 months of highly active antiretroviral therapy (HAART) and 2 lines of conventional chemotherapy (pegylated liposomal doxorubicin and docetaxel) was treated with lenalidomide on a compassionate use basis. He showed a rapid partial response without any substantial adverse effect but experienced relapse after 5 months of treatment, in a context of virologic failure. CONCLUSIONS AND RELEVANCE: Similar to our observation, good partial response without toxic effects has been reported in 3 patients with only skin involvement. Because immune reconstitution syndrome may occur in HIV-infected patients with KS undergoing HAART, KS improvement may be partly explained by immune recovery. An ongoing US phase 1/2 trial will better evaluate the efficacy and tolerance of lenalidomide in patients with HIV-related KS with and without visceral involvement.

Melorheostosis associated with peripheral form spondyloarthropathy: new image with 18-fluoride positron emission tomoscintigraphy coupled to computed tomography.

Melorheostosis is a rare benign bone pathology which can be responsible for incapacitating pain and bone deformations. Its imaging abnormalities are often typical. We describe here the case of a patient with melorheostosis involving the lower limbs, associated with a peripheral form of inflammatory spondyloarthropathy, who underwent 18FNa positron emission tomography coupled to a computed tomography scan. Our objective is to present this new image, to show the value of this new modality and emphasize its advantages compared to the 99mTechnetium bone scan.

Detection of 18fluoride sodium accumulation by positron emission tomography in calcified stenotic aortic valves.

Aortic valve stenosis progression rate is highly variable among patients and to date remains unpredictable. Evaluation of osteoblastic activity inside aortic valves may help identify patients with fast aortic stenosis progression rates and worse prognoses. Fluoride-18 sodium (FNa) is a clinically approved positron emission tomographic (PET) radiotracer with high and rapid bone uptake. The aim of this study was to test whether FNa accumulates in degenerative aortic valves and can be detected with PET imaging. Five patients with severe aortic stenosis and 10 patients free of aortic valvular calcium on computed tomography underwent PET imaging 40 minutes after the injection of 4 MBq/kg of FNa for oncologic or rheumatologic purposes. Maximal standard uptake values (SUVs) were measured retrospectively in aortic valves using PET imaging. Tissue-to-background ratios were calculated for each patient by dividing the maximal SUV measured in aortic valves by the mean SUV of blood. In patients with severe aortic stenosis, an intense accumulation of FNa was detected in aortic valve region on PET imaging, whereas only low activity was found in patients free of valvular calcification (median maximal SUV 2.6 g/ml/kg [interquartile range (IQR) 2.3 to 3.6] vs 2.0 g/ml/kg [IQR 1.7 to 2.2] and median tissue-to-background ratio 2.2 [IQR 2.0 to 2.7] vs 1.5 [IQR 1.5 to 1.7], respectively, p = 0.008 for both). Intraobserver variability for maximal SUV and tissue-to-background ratio in aortic valves was measured at 0.99 and interobserver variability at 0.98 and 0.97, respectively. In conclusion, in this pilot study, FNa accumulated in patients with severe aortic stenosis and could be quantified on PET imaging with good reproducibility. FNa PET imaging represents a promising imaging modality to evaluate osteoblastic activity inside calcified aortic valves.

Contraction delay of the RV outflow tract in patients with Brugada syndrome is dependent on the spontaneous ST-segment elevation pattern.

BACKGROUND: A growing body of evidence suggests that the arrhythmogenic substrate underlying Brugada syndrome (BrS) is located in the right ventricular outflow tract (RVOT), and electrophysiological abnormalities recently evidenced most commonly concur in conduction slowing. Also, imaging studies reported wall motion abnormalities of the RVOT in patients with BrS, with a various extent of RV remodeling. However, there are no data regarding a potential relationship between electrophysiological alterations and contraction abnormalities in BrS. OBJECTIVE: We aimed to assess (1) the potential relationship between contraction delays of the RV quantified by phase analysis of equilibrium radionuclide angiography (ERNA), and the spontaneous ST-segment elevation pattern; and (2) to evidence RV remodeling in patients with BrS. METHODS: Seventy patients with BrS and 18 control subjects were included in the study. For the purpose of the study, the spontaneous ST-segment elevation pattern was graded simultaneously to ERNA acquisition. RV contraction delays and amplitude were assessed using multiharmonic phase analysis of ERNA, and ventricular volumes and ejection fraction were assessed using gated blood-pool single photon emission computed tomography. RESULTS: RVOT contraction was delayed in patients with BrS, and RV contraction heterogeneity increased according to the pattern of ST-segment elevation, without impairment of the amplitude of contraction. RV volumes were greater in patients with BrS compared with control subjects, without impairment of the ejection fraction, whatever the ST-segment elevation pattern or the magnitude of contraction heterogeneity. CONCLUSION: In patients with BrS, we found a relationship between RV contraction heterogeneity and ST-segment pattern, providing evidence of a functional modulation of the arrhythmogenic substrate.

Novel neurotensin analogues for radioisotope targeting to neurotensin receptor-positive tumors.

The increased expression of the neurotensin (NT) receptor NTS1 by different cancer cells, such as pancreatic adenocarcinoma and ductal breast cancer cells, as compared to normal epithelium, offers the opportunity to target these tumors with radiolabeled neurotensin analogues for diagnostic or therapeutic purposes. The aim of the present study was to design and synthesize new neurotensin radioligands and to select a lead molecule with high in vivo tumor selectivity for further development. Two series of neurotensin analogues bearing DTPA were tested: a series of NT(8-13) analogues, with DTPA coupled to the α-NH(2), sharing the same peptide sequence with analogues previously developed for radiolabeling with technetium or rhenium, as well as an NT(6-13) series in which DTPA was coupled to the ε-NH(2) of Lys(6). Changes were introduced to stabilize the bonds between Arg(8)-Arg(9), Pro(10)-Tyr(11), and Tyr(11)-Ile(12) to provide metabolic stability. Structure-activity studies of NT analogues have shown that the attachment of DTPA induces an important loss of affinity unless the distance between the chelator and the NT(8-13) sequence, which binds to the NTS1 receptor, is increased. The doubly stabilized DTPA-NT-20.3 exhibits a high affinity and an elevated stability to enzymatic degradation. It shows specific tumor uptake and high tumor to blood, to liver, and to intestine activity uptake ratios and affords high-contrast planar and SPECT images in an animal model. The DTPA-NT-20.3 peptide is a promising candidate for imaging neurotensin receptor-positive tumors, such as pancreatic adenocarcinoma and invasive ductal breast cancer. Analogues carrying DOTA are being developed for yttrium-90 or lutetium-177 labeling.