PurposeThe chemokine receptor CXCR4 is a promising target for molecular imaging of CXCR4+ cell types, e.g. inflammatory cells, in cardiovascular diseases. We speculated that a specific CXCR4 ligand, [68Ga]pentixafor, along with novel techniques for motion correction, would facilitate the in vivo characterization of CXCR4 expression in small culprit and nonculprit coronary atherosclerotic lesions after acute myocardial infarction by motion-corrected targeted PET/CT.MethodsCXCR4 expression was analysed ex vivo in separately obtained arterial wall specimens. [68Ga]Pentixafor PET/CT was performed in 37 patients after stent-based reperfusion for a first acute ST-segment elevation myocardial infarction. List-mode PET data were reconstructed to five different datasets using cardiac and/or respiratory gating. Guided by CT for localization, the PET signals of culprit and various groups of nonculprit coronary lesions were analysed and compared.ResultsEx vivo, CXCR4 was upregulated in atherosclerotic lesions, and mainly colocalized with CD68+ inflammatory cells. In vivo, elevated CXCR4 expression was detected in culprit and nonculprit lesions, and the strongest CXCR4 PET signal (median SUVmax 1.96; interquartile range, IQR, 1.55–2.31) was observed in culprit coronary artery lesions. Stented nonculprit lesions (median SUVmax 1.45, IQR 1.23–1.88; P = 0.048) and hot spots in naive remote coronary segments (median SUVmax 1.34, IQR 1.23–1.74; P = 0.0005) showed significantly lower levels of CXCR4 expression. Dual cardiac/respiratory gating provided the strongest CXCR4 PET signal and the highest lesion detectability.ConclusionWe demonstrated the basic feasibility of motion-corrected targeted PET/CT imaging of CXCR4 expression in coronary artery lesions, which was triggered by vessel wall inflammation but also by stent-induced injury. This novel methodology may serve as a platform for future diagnostic and therapeutic clinical studies targeting the biology of coronary atherosclerotic plaque.Electronic supplementary materialThe online version of this article (10.1007/s00259-018-4076-2) contains supplementary material, which is available to authorized users.
Purpose Tracer kinetic modeling of tissue time activity curves and the individual input function based on arterial blood sampling and metabolite correction is the gold standard for quantitative characterization of microglia activation by PET with the translocator protein (TSPO) ligand 18 F-GE-180. This study tested simplified methods for quantification of 18 F-GE-180 PET. Methods Dynamic 18 F-GE-180 PET with arterial blood sampling and metabolite correction was performed in five healthy volunteers and 20 liver-transplanted patients. Population-based input function templates were generated by averaging individual input functions normalized to the total area under the input function using a leave-one-out approach. Individual population-based input functions were obtained by scaling the input function template with the individual parent activity concentration of 18 F-GE-180 in arterial plasma in a blood sample drawn at 27.5 min or by the individual administered tracer activity, respectively. The total 18 F-GE-180 distribution volume (V T) was estimated in 12 regions-of-interest (ROIs) by the invasive Logan plot using the measured or the population-based input functions. Late ROI-to-whole-blood and ROI-to-cerebellum ratio were also computed. Results Correlation with the reference V T (with individually measured input function) was very high for V T with the populationbased input function scaled with the blood sample and for the ROI-to-whole-blood ratio (Pearson correlation coefficient = 0.989 ± 0.006 and 0.970 ± 0.005). The correlation was only moderate for V T with the population-based input function scaled with tracer activity dose and for the ROI-to-cerebellum ratio (0.653 ± 0.074 and 0.384 ± 0.177). Reference V T , population-based V T with scaling by the blood sample, and ROI-to-whole-blood ratio were sensitive to the TSPO gene polymorphism. Population-based V T with scaling to the administered tracer activity and the ROI-to-cerebellum ratio failed to detect a polymorphism effect. Conclusion These results support the use of a population-based input function scaled with a single blood sample or the ROI-towhole-blood ratio at a late time point for simplified quantitative analysis of 18 F-GE-180 PET.
AimsHigh-energy resolution and sensitivity of novel cadmium-zinc-telluride (CZT) detector equipped SPECT systems facilitate simultaneous imaging of multiple isotopes and may enhance the detection of molecular/cellular signals. This may refine the detection of endocarditis. This study was designed to determine the feasibility and diagnostic accuracy of simultaneous imaging of inflammation with 111 In-labeled white blood cells (WBCs) and myocardial perfusion with 99m Tc-sestamibi, for localization of WBCs relative to the valve plane in suspected endocarditis. Methods and resultsA dedicated cardiac CZT camera (Discovery 530c, GE Healthcare) was employed. Anthropomorphic thorax phantom studies were followed by clinical studies in 34 patients with suspected infection of native valves (n ¼ 12) or implants (n ¼ 22 In activity as high as 2.5* 99m Tc activity. In patients, image quality was superior for CZT imaging vs. conventional SPECT-CT and planar scintigraphy (P , 0.01). Cadmium-zinc-telluride dual isotope imaging improved reader confidence for detection of inflammatory foci. Diagnostic accuracy based on surgery or Duke Criteria during follow-up was highest for CZT imaging (P , 0.001). ConclusionNovel CZT SPECT technology improves the accuracy of molecular/cellular cardiac imaging. Simultaneous multi-isotope imaging with 111 In and 99m Tc is feasible and aids in the workup of suspected endocarditis.--
Purpose Calcineurin inhibitors (CNI) can cause long-term impairment of brain function. Possible pathomechanisms include alterations of the cerebral immune system. This study used positron emission tomography (PET) imaging with the translocator protein (TSPO) ligand 18F-GE-180 to evaluate microglial activation in liver-transplanted patients under different regimens of immunosuppression. Methods PET was performed in 22 liver-transplanted patients (3 CNI free, 9 with low-dose CNI, 10 with standard-dose CNI immunosuppression) and 9 healthy controls. The total distribution volume (VT) estimated in 12 volumes-of-interest was analyzed regarding TSPO genotype, CNI therapy, and cognitive performance. Results In controls, VT was about 80% higher in high affinity binders (n = 5) compared to mixed affinity binders (n = 3). Mean VT corrected for TSPO genotype was significantly lower in patients compared to controls, especially in patients in whom CNI dose had been reduced because of nephrotoxic side effect. Conclusion Our results provide evidence of chronic suppression of microglial activity in liver-transplanted patients under CNI therapy especially in patients with high sensitivity to CNI toxicity.
(1) Background: To comparatively analyze the uptake of hepatocellular carcinoma (HCC) on pre-therapeutic imaging modalities, the arterial phase multi-detector computed tomography (MDCT), the parenchymal phase C-arm computed tomography (CACT), the Technetium99m-macroaggregates of human serum albumin single-photon emission computed tomography/computed tomography (SPECT/CT), and the correlation to the post-therapeutic Yttrium90 positron emission tomography/computed tomography (PET/CT) in patients with selective internal radiation therapy (SIRT). (2) Methods: Between September 2013 and December 2016, 104 SIRT procedures were performed at our institution in 74 patients with HCC not suitable for curative surgery or ablation. Twenty-two patients underwent an identical sequence of pre-therapeutic MDCT, CACT, SPECT/CT, and post-therapeutic PET/CT with a standardized diagnostic and therapeutic protocol. In these 22 patients, 25 SIRT procedures were evaluated. The uptake of the HCC was assessed using tumor-background ratio (TBR). Therefore, regions of interest were placed on the tumor and the adjacent liver tissue on MDCT (TBRMDCT), CACT (TBRCACT), SPECT/CT (TBRSPECT/CT), and PET/CT (TBRPET/CT). Comparisons were made with the Friedman test and the Nemenyi post-hoc test. Correlations were analyzed using Spearman’s Rho and the Benjamini–Hochberg method. The level of significance was p < 0.05. (3) Results: TBR on MDCT (1.4 ± 0.3) was significantly smaller than on CACT (1.9 ± 0.6) and both were significantly smaller compared to SPECT/CT (4.6 ± 2.0) (pFriedman-Test < 0.001; pTBRMDCT/TBRCACT = 0.012, pTBRMDCT/TBRSPECT/CT < 0.001, pTBRCACT/TBRSPECT/CT < 0.001). There was no significant correlation of TBR on MDCT with PET/CT (rTBRMDCT/TBRPET/CT = 0.116; p = 0.534). In contrast, TBR on CACT correlated to TBR on SPECT/CT (rTBRCACT/TBRSPECT/CT = 0.489; p = 0.004) and tended to correlate to TBR on PET/CT (rTBRCACT/TBRPET/CT =0.365; p = 0.043). TBR on SPECT/CT correlated to TBR on PET/CT (rTBRSPECT/CT/TBRPET/CT= 0.706; p < 0.001) (4) Conclusion: The uptake assessment on CACT was in agreement with SPECT/CT and might be consistent with PET/CT. In contrast, MDCT was not comparable to CACT and SPECT/CT, and had no correlation with PET/CT due to the different application techniques. This emphasizes the value of the CACT, which has the potential to improve the dosimetric assessment of the tumor and liver uptake for SIRT.
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