Purpose
The aim of this study was to demonstrate the potential of Ga-68-labeled macrocycle (DOTA-en-pba) conjugated with phenylboronic vector for tumor recognition by positron emission tomography ...(PET), based on targeting of the overexpressed sialic acid (Sia).
Procedures
The imaging reporter DOTA-en-pba was synthesized and labeled with Ga-68 at high efficiency. Cell binding assay on Mel-C and B16-F10 melanoma cells was used to evaluate melanin production and Sia overexpression to determine the best model for demonstrating the capability of
68
GaDOTA-en-pba to recognize tumors. The
in vivo
PET imaging was done with B16-F10 tumor-bearing SCID mice injected with
68
GaDOTA-en-pba intravenously. Tumor, blood, and urine metabolites were assessed to evaluate the presence of a targeting agent.
Results
The affinity of
68
GaDOTA-en-pba to Sia was demonstrated on B16-F10 melanoma cells, after the production of melanin as well as Sia overexpression was proved to be up to four times higher in this cell line compared to that in Mel-C cells. Biodistribution studies in B16-F10 tumor-bearing SCID mice showed blood clearance at the time points studied, while uptake in the tumor peaked at 60 min post-injection (6.36 ± 2.41 % ID/g). The acquired PET images were in accordance with the
ex vivo
biodistribution results. Metabolite assessment on tumor, blood, and urine samples showed that
68
GaDOTA-en-pba remains unmetabolized up to at least 60 min post-injection.
Conclusions
Our work is the first attempt for
in vivo
imaging of cancer by targeting overexpression of sialic acid on cancer cells with a radiotracer in PET.
To test the hypothesis that virtual functional assessment index (vFAI) is related with regional flow parameters derived by quantitative positron emission tomography (PET) and can be used to assess ...abnormal vasodilating capability in coronary vessels with stenotic lesions at coronary computed tomography angiography (CCTA).
vFAI, stress myocardial blood flow (MBF), and myocardial flow reserve (MFR) were assessed in 78 patients (mean age 62.2 ± 7.7 years) with intermediate pre-test likelihood of coronary artery disease (CAD). Coronary stenoses ≥50% were considered angiographically significant. PET was considered positive for significant CAD, when more than one contiguous segments showed stress MBF ≤2.3 mL/g/min for 15O-water or <1.79 mL/g/min for 13N-ammonia. MFR thresholds were ≤2.5 and ≤2.0, respectively. vFAI was lower in vessels with abnormal stress MBF (0.76 ± 0.10 vs. 0.89 ± 0.07, P < 0.001) or MFR (0.80 ± 0.10 vs. 0.89 ± 0.07, P < 0.001). vFAI had an accuracy of 78.6% and 75% in unmasking abnormal stress MBF and MFR in 15O-water and 82.7% and 71.2% in 13N-ammonia studies, respectively. Addition of vFAI to anatomical CCTA data increased the ability for predicting abnormal stress MBF and MFR in 15O-water studies AUCccta + vfai = 0.866, 95% confidence interval (CI) 0.783-0.949; P = 0.013 and AUCccta + vfai = 0.737, 95% CI 0.648-0.825; P = 0.007, respectively. An incremental value was also demonstrated for prediction of stress MBF (AUCccta + vfai = 0.887, 95% CI 0.799-0.974; P = 0.001) in 13N-ammonia studies. A similar trend was recorded for MFR (AUCccta + vfai = 0.780, 95% CI 0.632-0.929; P = 0.13).
vFAI identifies accurately the presence of impaired vasodilating capability. In combination with anatomical data, vFAI enhances the diagnostic performance of CCTA.
Remote kidney damage is a sequel of hepatic ischemia-reperfusion (I/R) injury. Silibinin is the main ingredient of the milk thistle plant seed extract with known antioxidant and hepatoprotective ...activity. Our study investigates the nephroprotective potential of intravenously administered silibinin, as a lyophilized SLB-hydoxypropyl-beta-cyclodextrin product, in hepatic I/R injury.
63 Wistar rats were divided into three groups: Sham (virtual intervention); Control (45 min ischemia and reperfusion); and Silibinin (200 μL intravenous silibinin administration after 45 min of ischemia). Kidney tissues were collected to determine TNF-α, M30 and histopathological changes at predetermined time intervals.
Comparing Sham vs. Control groups, proved that hepatic I/R injury increased renal TNF-α and M30 expression. Deterioration was observed in hyperemia/filtration of renal parenchyma and tubules, cortical filtration, tubular necrosis and edema (tissue swelling index). Intravenous silibinin administration and comparison of the Control vs. Silibinin groups showed a statistically significant decrease in TNF-α levels at 240 min following I/R (p < 0.0001), and in M30 at 180 min (p = 0.03) and 240 min (p < 0.0001). Renal parameters have significantly decreased in: hyperemia/filtration of renal parenchyma at 120 min (p = 0.003), 180 min (p = 0.0001) and 240 min (p = 0.0002); hyperemia/filtration of renal tubules at 120 min (p = 0.02), 180 min (p = 0.0001) and 240 min (p = 0.0005); cortical filtration (240 min - p = 0.005); tubular necrosis (240 min - p = 0.021); and edema (240 min - p = 0.001).
Our study confirms that hepatic I/R injury causes remote renal damage while the intravenous administration of silibinin leads to statistically significant nephroprotective action.
The concept of a hepato-splenic axis has recently been put forward. We aimed to investigate whether hepatic and splenic metabolic activities are linked, and if splenic metabolic activity is increased ...in non-alcoholic fatty liver disease (NAFLD). Blood clearance rates of phosphorylated
F-fluorodeoxyglucose were measured in the spleen and liver from dynamic PET using Gjedde-Patlak-Rutland graphical analysis and abdominal aorta for input function in 59 patients undergoing routine PET/CT. Plot gradient (Ki), which represents blood clearance, was divided by intercept (V(0)), which represents tissue FDG distribution volume, and multiplied by blood glucose to give glucose uptake rate per unit tracer distribution volume (MRglu). In addition, liver-to-spleen raw count rate ratio was plotted against time, and gradient (b) divided by intercept (A) to obtain hepatic-to-splenic blood clearance ratio independent of aortic input function. Hepatic steatosis was inferred when hepatic CT density was ≤40 HU. There was no difference in splenic MRglu between 8 patients with inactive lympho-proliferative disease (LPD) as identified by negative PET/CT, 25 with non-haematological malignancy and 13 with normal PET/CT. It was significantly increased in 13 with active LPD, who were therefore excluded, along with 3 more with type-2 diabetes mellitus. Splenic MRglu was higher in patients with hepatic steatosis (4.0±1.6; n = 12) than without (2.6±1.7 μmol/min/100 ml; P = 0.02) and correlated inversely with hepatic CT density (r = -0.49; P<0.001). Hepatic and splenic Ki/V(0) correlated (r = 0.52; P<0.01) in 22 patients in whom the correlation coefficient between b/A and hepatic-to-splenic Ki/V(0) ratio was 0.99 and in whom, therefore, input function errors in graphical analysis could be discounted. In men, splenic longitudinal diameter correlated significantly with hepatic CT density (r = -0.35; P = 0.046), hepatic MRglu (r = 0.44; P = 0.005) and splenic MRglu (r = 0.35; P = 0.046). Splenic Ki/V(0) correlated positively with blood glucose, suggesting sensitivity to insulin. We conclude that hepatic and splenic metabolic activities are linked and that a speculative mechanism, which deserves further investigation, is shared insulin sensitivity. Splenic MRglu and spleen size are increased in NAFLD.
Aims:
In this study, we evaluate the efficacy of SmartFFR, a new functional index of coronary stenosis severity compared with gold standard invasive measurement of fractional flow reserve (FFR). We ...also assess the influence of the type of simulation employed on smartFFR (i.e. Fluid Structure Interaction vs. rigid wall assumption).
Methods and Results:
In a dataset of 167 patients undergoing either computed tomography coronary angiography (CTCA) and invasive coronary angiography or only invasive coronary angiography (ICA), as well as invasive FFR measurement, SmartFFR was computed after the 3D reconstruction of the vessels of interest and the subsequent blood flow simulations. 202 vessels were analyzed with a mean total computational time of seven minutes. SmartFFR was used to process all models reconstructed by either method. The mean FFR value of the examined dataset was 0.846 ± 0.089 with 95% CI for the mean of 0.833–0.858, whereas the mean SmartFFR value was 0.853 ± 0.095 with 95% CI for the mean of 0.84–0.866. SmartFFR was significantly correlated with invasive FFR values (R
CCTA
= 0.86,
p
CCTA
< 0.0001, R
ICA
= 0.84,
p
ICA
< 0.0001,
R
overall
= 0.833,
p
overall
< 0.0001), showing good agreement as depicted by the Bland-Altman method of analysis. The optimal SmartFFR threshold to diagnose ischemia was ≤0.83 for the overall dataset, ≤0.83 for the CTCA-derived dataset and ≤0.81 for the ICA-derived dataset, as defined by a ROC analysis (AUC
overall
= 0.956,
p
< 0.001, AUC
ICA
= 0.975,
p
< 0.001, AUC
CCTA
= 0.952,
p
< 0.001).
Conclusion:
SmartFFR is a fast and accurate on-site index of hemodynamic significance of coronary stenosis both at single coronary segment and at two or more branches level simultaneously, which can be applied to all CTCA or ICA sequences of acceptable quality.
Familial dyslipidemias of either heterozygous (heFH) or combined (FCH) type lead to accelerated atherogenesis and increased cardiovascular risk.
The aim of this study was to investigate in ...statin-naïve adult patients with familial dyslipidemias whether inflammatory activation and liver, spleen and bone marrow metabolic activity differ compared with normolipidemic subjects and between dyslipidemic groups.
Fourteen patients with FCH, 14 with heFH, and 14 normolipidemic individuals were enrolled. Serum lipids, high-sensitivity C-reactive protein, and fibrinogen levels were measured, followed by 18F-fluorodeoxyglucose positron-emission tomography/computed tomography imaging. Radiotracer uptake in the aortic wall, spleen, bone marrow, and liver was quantified as tissue-to-background ratio (TBR).
Patients with heFH had significantly higher low-density lipoprotein levels compared with those with FCH and controls (P < .001). However, aortic TBRs were higher in FCH compared with heFH patients and controls (P = .02 and P < .001, respectively). FCH patients exhibited higher FDG uptake in the spleen compared with controls (P = .05). In addition, FCH exhibited higher bone marrow FDG uptake compared with heFH patients and controls (P = .03 and P = .02, respectively). FCH had higher liver uptake compared with heFH patients and controls (P < .001 for both). Significant correlations were observed between inflammatory biomarkers and imaging indices as well as between aortic TBR and FDG uptake of hematopoietic organs and liver.
Systemic, as well as vascular inflammation and spleen, bone marrow, and hepatic metabolic activity are increased in patients with FCH despite lower levels of low-density lipoprotein.
•This is the first study to investigate vascular inflammation in familial combined dyslipidemia.•Liver, bone marrow, and spleen metabolic activity were also evaluated.•Familial combined hyperlipidemia exhibits higher vascular activity compared with heterozygous familial hypercholesterolemia.•Correlations between vascular and hematopoietic tissues metabolic activity were noted.
Objectives We studied whether an increase in adenosine dose overcomes caffeine antagonism on adenosine-mediated coronary vasodilation. Background Caffeine is a competitive antagonist at the adenosine ...receptors, but it is unclear whether caffeine in coffee alters the actions of exogenous adenosine, and whether the antagonism can be surmounted by increasing the adenosine dose. Methods Myocardial perfusion scintigraphy (MPS) was used to assess adenosine-induced hyperemia in 30 patients before (baseline) and after coffee ingestion (caffeine). At baseline, patients received 140 μg/kg/min of adenosine combined with low-level exercise. For the caffeine study, 12 patients received 140 μg/kg/min of adenosine (standard) and 18 patients received 210 μg/kg/min (high dose) after caffeine intake (200 mg). Myocardial perfusion was assessed semiquantitatively and quantitatively, and perfusion defect was characterized according to the presence of reversibility. Results Caffeine reduced the magnitude of perfusion abnormality induced by standard adenosine as measured by the summed difference score (SDS) (12.0 ± 4.4 at baseline vs. 4.1 ± 2.1 after caffeine, p < 0.001) as well as defect size (18% 3% to 38% vs. 8% 0% to 22%, p < 0.01), whereas it had no effect on the abnormalities caused by high-dose adenosine (SDS, 7.7 ± 4.0 at baseline vs. 7.8 ± 4.2 after caffeine, p = 0.7). There was good agreement between baseline and caffeine studies for segmental defect category (kappa = 0.72, 95% confidence interval: 0.65 to 0.79) in the high-dose group. An increase in adenosine after caffeine intake was well tolerated. Conclusions Caffeine in coffee attenuates adenosine-induced coronary hyperemia and, consequently, the detection of perfusion abnormality by adenosine MPS. This can be overcome by increasing the adenosine dose without compromising test tolerability.
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