[Clinical significance of neuroendocrine tumors : Incidence, symptoms, diagnosis, stage, and prognostic factors and their influence on disease management]. / Klinische Bedeutung von neuroendokrinen Tumoren : Häufigkeit, Symptome, Diagnose und Stadien und prognostische Faktoren und deren Einfluss auf das Krankheitsmanagement.

BACKGROUND: Neuroendocrine neoplasms (NEN) are heterogenous with an increasing incidence in recent years. OBJECTIVES: Overview on incidence, symptoms, diagnostics, grading, imaging and prognostic determinants, including factors having an impact on therapeutic management. METHODS: Review on current literature, including original articles, reviews, guidelines and expert opinions. RESULTS: NEN are mainly located in the gastrointestinal tract and their incidence has increased in recent years, mainly due to improved diagnostics, e.g., cross-sectional imaging. Clinical characteristics include hormone excess syndromes (carcinoid syndrome). Laboratory markers such as chromogranin A are commonly used as part of routine diagnostics, followed by endoscopic and endosonographic procedures, which also allow biopsies to be obtained. Tumor spread can be determined by contrast-enhanced computed tomography/magnetic resonance imaging (CT/MRI) or somatostatin receptor (SSRT)-PET/CT (positron emission tomography). Prognostic factors include Ki67 index, type, and grading. Resection with curative intent is the therapy of choice. In a metastasized setting, SSRT-directed treatment approaches are favored, while in dedifferentiated NEN, conventional chemotherapy is needed. CONCLUSION: A broad diagnostic armamentarium can be offered to NEN patients and the improved diagnostic procedures have most likely caused a raising incidence in recent years. Among others, prognostic factors are Ki67 and NEN subtypes; these clinical determinants also have an impact on patient management.

In Vivo Functional Assessment of Sodium-Glucose Cotransporters (SGLTs) Using [18F]Me4FDG PET in Rats.

Background: Mediating glucose absorption in the small intestine and renal clearance, sodium glucose cotransporters (SGLTs) have emerged as an attractive therapeutic target in diabetic patients. A substantial fraction of patients, however, only achieve inadequate glycemic control. Thus, we aimed to assess the potential of the SGLT-targeting PET radiotracer alpha-methyl-4-deoxy-4-[18F]fluoro-D-glucopyranoside ([18F]Me4FDG) as a noninvasive intestinal and renal biomarker of SGLT-mediated glucose transport. Methods: We investigated healthy rats using a dedicated small animal PET system. Dynamic imaging was conducted after administration of the reference radiotracer 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG), or the SGLT-targeting agent, [18F]Me4FDG either directly into the digestive tract (for assessing intestinal absorption) or via the tail vein (for evaluating kidney excretion). To confirm the specificity of [18F]Me4FDG and responsiveness to treatment, a subset of animals was also pretreated with the SGLT inhibitor phlorizin. In this regard, an intraintestinal route of administration was used to assess tracer absorption in the digestive tract, while for renal assessment, phlorizin was injected intravenously (IV). Results: Serving as reference, intestinal administration of [18F]FDG led to slow absorption with retention of 89.2 ± 3.5% of administered radioactivity at 15 min. [18F]Me4FDG, however, was rapidly absorbed into the blood and cleared from the intestine within 15 min, leading to markedly lower tracer retention of 18.5 ± 1.2% (P < 0.0001). Intraintestinal phlorizin led to marked increase of [18F]Me4FDG uptake (15 min, 99.9 ± 4.7%; P < 0.0001 vs. untreated controls), supporting the notion that this PET agent can measure adequate SGLT inhibition in the digestive tract. In the kidneys, radiotracer was also sensitive to SGLT inhibition. After IV injection, [18F]Me4FDG reabsorption in the renal cortex was significantly suppressed by phlorizin when compared to untreated animals (%ID/g at 60 min, 0.42 ± 0.10 vs. untreated controls, 1.20 ± 0.03; P < 0.0001). Conclusion: As a noninvasive read-out of the concurrent SGLT expression in both the digestive tract and the renal cortex, [18F]Me4FDG PET may serve as a surrogate marker for treatment response to SGLT inhibition. As such, [18F]Me4FDG may enable improvement in glycemic control in diabetes by PET-based monitoring strategies.

Metabolic substrate shift in human induced pluripotent stem cells during cardiac differentiation: Functional assessment using in vitro radionuclide uptake assay.

BACKGROUND: Recent developments in cellular reprogramming technology enable the production of virtually unlimited numbers of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM). Although hiPSC-CM share various characteristic hallmarks with endogenous cardiomyocytes, it remains a question as to what extent metabolic characteristics are equivalent to mature mammalian cardiomyocytes. Here we set out to functionally characterize the metabolic status of hiPSC-CM in vitro by employing a radionuclide tracer uptake assay. MATERIAL AND METHODS: Cardiac differentiation of hiPSC was induced using a combination of well-orchestrated extrinsic stimuli such as WNT activation (by CHIR99021) and BMP signalling followed by WNT inhibition and lactate based cardiomyocyte enrichment. For characterization of metabolic substrates, dual tracer uptake studies were performed with 18F­2­fluoro­2­deoxy­d­glucose (18F-FDG) and 125I­ß­methyl­iodophenyl­pentadecanoic acid (125I-BMIPP) as transport markers of glucose and fatty acids, respectively. RESULTS: After cardiac differentiation of hiPSCs, in vitro tracer uptake assays confirmed metabolic substrate shift from glucose to fatty acids that was comparable to those observed in native isolated human cardiomyocytes. Immunostaining further confirmed expression of fatty acid transport and binding proteins on hiPSC-CM. CONCLUSIONS: During in vitro cardiac maturation, we observed a metabolic shift to fatty acids, which are known as a main energy source of mammalian hearts, suggesting hi-PSC-CM as a potential functional phenotype to investigate alteration of cardiac metabolism in cardiac diseases. Results also highlight the use of available clinical nuclear medicine tracers as functional assays in stem cell research for improved generation of autologous differentiated cells for numerous biomedical applications.

Optimization of imaging protocols for myocardial blood flow (MBF) quantification with 18F-flurpiridaz PET.

The new PET tracer, 18F-flurpiridaz, with high myocardial extraction allows quantitative myocardial blood flow (MBF) estimation from dynamic PET data and tracer kinetic modeling. The goal of this study is to determine the optimal imaging protocols and parameters using a realistic simulation study. The time activity curves (TACs) of different tissue organs from a 30-s infusion time (IT) of 18F-flurpiridaz in a dynamic PET study were extracted from a previous study. The TACs at different time points were incorporated in a series of realistic 3D XCAT phantoms from which the parameters of a 2-compartment model and the 'true' MBF of 18F-flurpiridaz were determined. The compartmental model was used to generate TACs from 7 additional ITs. PET projection data from the XCAT phantoms were generated using Monte Carlo simulation. They were reconstructed using an OS-EM reconstruction algorithm with different update number (N) to obtain dynamic PET images. The blood and myocardial TACs were derived from the dynamic images from which the MBF and %MBF error was estimated. The %MBF error decreases with increasing N of the OS-EM and levels off after ∼42. The 30-s IT gave the smallest %MBF error that decreases from ∼0.57% to ∼19.40%. The MBF for 2-min, 4-min, 8-min and 16-min IT were statistically significant different from the MBF for 30-s IT (P<0.05). Too fast or too slow infusion time gave higher %MBF error. The optimal imaging protocol in dynamic 18F-flurpiridaz PET for accurate quantitative MBF estimation was 30-s IT and N of ∼42 for the OS-EM.

Assessment of coronary flow reserve using a combination of planar first-pass angiography and myocardial SPECT: Comparison with myocardial (15)O-water PET.

UNLABELLED: Coronary flow reserve (CFR), defined as the ratio of maximum coronary flow increase from baseline resting blood flow, is one of the most sensitive parameters to detect early signs of coronary arteriosclerosis at the microvascular level. Myocardial perfusion PET is a well-established technology for CFR measurement, however, availability is still limited. The aim of this study is to introduce and validate myocardial flow reserve measurement by myocardial perfusion SPECT. METHODS: Myocardial perfusion SPECT at rest and ATP stress (0.16mg/Kg/min) was performed in 10 patients with known coronary artery disease. Immediately after the injection of Tc-99m sestamibi (MIBI), left ventricular (LV) dynamic planar angiographic data were obtained for 90s. Coronary flow reserve index as measured by MIBI SPECT (CFRMIBI) was calculated as follows: CFRMIBI=CmsSbmb/CmbSbms, where subscripts b, s, Cm, and Sbm indicate baseline, during stress, myocardial counts with MIBI SPECT, and integral of LV counts with first pass angiography, respectively. Additionally, standard stress/rest (15)O-water PET to estimate CFR was performed in all patients as standard of reference. RESULTS: CFRMIBI increased in conjunction with CFR, but underestimated blood flow at high flow rates. The relationship between CFRMIBI (Y) and CFRPET (X) was well fitted as follows: Y=1.40x(1-exp(1.79/x)) (r=0.84). CONCLUSIONS: The index of CFRMIBI reflects the CFR by (15)O-water PET but underestimates flow at high flows, maybe as a reflection of pharmacokinetic limitations of MIBI.

Assessment of tumor heterogeneity in treatment-naïve adrenocortical cancer patients using (18)F-FDG positron emission tomography.

As an orphan malignancy, only limited treatment options are available in adrenocortical carcinoma (ACC). Non-invasive risk assessment has not been described but may be of value to stratify patients for treatment. We aimed to evaluate the potential value of intra-individual tumor heterogeneity as assessed by (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography/computed tomography (PET/CT) for outcome prediction in treatment-naïve ACC patients. Ten patients with primary diagnosis of ACC were included in this study. Prior to any treatment initiation, baseline (18)F-FDG PET scans were performed. Tumor staging was performed using the European Network for the Study of Adrenal Tumors (ENS@T). Intratumoral heterogeneity of the primary tumor was assessed by manual segmentation using conventional PET parameters (standardized uptake values and tumor-to-liver ratios) and textural features. The impact of tumoral heterogeneity based on pre-therapeutic (18)F-FDG PET to predict progression-free (PFS) and overall survival (OS) was evaluated by receiver operating characteristic analysis. On average, tumor recurrence or progression was detected after median of 561 days (range 71-1434 days) after the pre-therapeutic baseline PET scan. 50 % of the patients died of ACC within the follow-up period (mean 983 ± 404 days). Pre-therapeutic tumor volume was associated with PFS (r = -0.67, p = 0.05) and Ki67 index with OS (r = -0.66, p = 0.04). ENS@T tumor stage was the only parameter to correlate with both PFS and OS (r = -0.82, p = 0.001, and r = -0.72, p = 0.01, respectively). In the subgroup of patients without distant metastases (ENS@T stages II and III), age and pre-therapeutic tumor volume correlated significantly with PFS (r = 0.96, p = 0.01 and r = -0.93, p = 0.02, respectively) and OS (r = 0.95, p = 0.02 and r = -0.90, p = 0.04, respectively). None of the investigated classic or textural PET parameters predicted PFS or OS. In this pilot study in treatment-naïve ACC patients, conventional (18)F-FDG PET-derived parameters and textural tumor heterogeneity features were not suitable to identify high-risk patients.

Heart and systemic effects of statin pretreatment in a rat model of abdominal sepsis. Assessment by Tc99m-sestamibi biodistribition.

PURPOSE: To evaluate the heart and the Tc-99m-sestamibi biodistribution after statin pretreatment in a rat model of abdominal sepsis. METHODS: Twenty-four Wistar rats were randomly distributed into four groups (n=6 per group): 1) sepsis with simvastatin treatment, 2) sepsis with vehicle, 3) sham control with simvastatin and 4) sham control with vehicle. 24 hours after cecal ligation and puncture rats received 1.0MBq of Tc-99m-sestamibi i.v. 30min after, animals were euthanized for ex-vivo tissue counting and myocardium histological analysis. RESULTS: Myocardial histologic alterations were not detected 24 hours post-sepsis. There was significantly increased cardiac Tc-99m-sestamibi activity in the sepsis group with simvastatin treatment (1.9±0.3%ID/g, p<0.001) in comparison to the sepsis group+vehicle (1.0±0.2%ID/g), control sham group+ simvastatin (1.2±0.3%ID/g) and control sham group (1.3±0.2%ID/g). Significant Tc-99m-sestamibi activity in liver, kidney and lungs was also detected in the sepsis group treated with simvastatinin comparison to the other groups. CONCLUSIONS: Statin treatment altered the biodistribution of Tc-99m-sestamibi with increased cardiac and solid organ activity in rats with abdominal sepsis, while no impact on controls. Increased myocardial tracer activity may be a result of a possible protection effect due to increased tissue perfusion mediated by statins.

Heart and systemic effects of statin pretreatment in a rat model of abdominal sepsis. Assessment by Tc99m-sestamibi biodistribition

PURPOSE: To evaluate the heart and the Tc-99m-sestamibi biodistribution after statin pretreatment in a rat model of abdominal sepsis. METHODS: Twenty-four Wistar rats were randomly distributed into four groups (n=6 per group): 1) sepsis with simvastatin treatment, 2) sepsis with vehicle, 3) sham control with simvastatin and 4) sham control with vehicle. 24 hours after cecal ligation and puncture rats received 1.0MBq of Tc-99m-sestamibi i.v. 30min after, animals were euthanized for ex-vivo tissue counting and myocardium histological analysis. RESULTS: Myocardial histologic alterations were not detected 24 hours post-sepsis. There was significantly increased cardiac Tc-99m-sestamibi activity in the sepsis group with simvastatin treatment (1.9±0.3%ID/g, p<0.001) in comparison to the sepsis group+vehicle (1.0±0.2%ID/g), control sham group+ simvastatin (1.2±0.3%ID/g) and control sham group (1.3±0.2%ID/g). Significant Tc-99m-sestamibi activity in liver, kidney and lungs was also detected in the sepsis group treated with simvastatinin comparison to the other groups. CONCLUSIONS: Statin treatment altered the biodistribution of Tc-99m-sestamibi with increased cardiac and solid organ activity in rats with abdominal sepsis, while no impact on controls. Increased myocardial tracer activity may be a result of a possible protection effect due to increased tissue perfusion mediated by statins. .

Assessment of the 18F-labeled PET tracer LMI1195 for imaging norepinephrine handling in rat hearts.

UNLABELLED: A novel (18)F-labeled tracer, LMI1195 (N-[3-bromo-4-(3-(18)F-fluoro-propoxy)-benzyl]-guanidine), is being developed for sympathetic nerve imaging; its high specificity for neural uptake-1 mechanism has previously been demonstrated in cell associative studies and in rabbit and nonhuman primate studies assessing heart uptake. The aim of this study was to investigate the mechanisms of (18)F-LMI1195 cardiac uptake in the rat, which is known to contain norepinephrine uptake mechanisms beyond uptake-1. METHODS: Tracer accumulation in the heart was studied over time after intravenous administration of (18)F-LMI1195 in healthy male Wistar rats by quantitative in vivo PET imaging. The uptake mechanism was assessed by pretreatment with the nonselective norepinephrine uptake-1 and norepinephrine uptake-2 inhibitor phenoxybenzamine (50 mg/kg intravenously; n = 4), the selective norepinephrine uptake-1 inhibitor desipramine (2 mg/kg intravenously; n = 4), or saline control (intravenously; n = 4). RESULTS: (18)F-LMI1195 produced high and sustained heart uptake allowing clear delineation of the left ventricular wall over 60 min after tracer administration. Pretreatment with phenoxybenzamine markedly reduced the (18)F-LMI1195 cardiac uptake when compared with controls. In contrast, there was preserved (18)F-LMI1195 uptake after desipramine pretreatment. CONCLUSION: In rats, cardiac uptake of (18)F-LMI1195 was significantly inhibited by phenoxybenzamine but not desipramine, suggesting (18)F-LMI1195 is a substrate for the uptake-2 mechanism and is consistent with the rat heart having a dominant level of the mechanism.

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.

Evaluation of a novel (18)F-labeled positron-emission tomography perfusion tracer for the assessment of myocardial infarct size in rats.

BACKGROUND: The goal of this study was to evaluate a new (18)F-labeled positron-emission tomography (PET) perfusion tracer, (18)F BMS747158-02, for the assessment of myocardial infarct (MI) size. METHODS AND RESULTS: Wistar rats were studied 24 hours after ligation of the left coronary artery either permanently (n=15) or transiently (n=16) for 30 minutes. Seven nonoperated rats were studied as controls. The rats were injected with 37 MBq of (18)F BMS747158-02 and imaged with a small animal PET scanner for 20 minutes. Polar maps were generated for measurement of PET defect size, and left ventricular systolic and diastolic volumes were assessed in gated images. As a reference, MI size was determined by 2,3,5-triphenyltetrazolium chloride staining of left ventricular tissue samples. Permanent or transient ligation of the left coronary artery produced transmural or subendocardial MI of variable sizes, respectively. In normal rats, PET imaging demonstrated intense and homogeneous uptake of (18)F BMS747158-02 throughout the myocardium. After ligation, sharply defined perfusion defects were present. Throughout the imaging period, the defect size correlated closely with the MI size either after permanent (r=0.88; P<0.01; mean difference, 1.86%) or transient (r=0.92; P<0.01; mean difference, 2.16%) ligation of the left coronary artery. Moreover, reduction of left ventricular systolic function measured with PET correlated with the MI size (r=-0.81; P<0.01; n=23). CONCLUSIONS: Myocardial (18)F BMS747158-02 PET imaging provides excellent image quality and uptake properties, enabling accurate evaluation of MI size and left ventricular function in rats. It is a promising technique for evaluation of MI size in clinical trials.

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.

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.

Electrocardiographic gated (99m)Tc-MIBI SPECT for functional assessment of patients after coronary artery bypass surgery: comparison of wall thickening and wall motion analysis.

UNLABELLED: Abnormal septal motion after coronary artery bypass graft surgery (CABG) is a common finding. This study was undertaken to investigate the change in various global and regional ventricular function parameters measured by gated myocardial perfusion SPECT after surgery and to determine which quantitative parameter of WT and WM is more appropriate for the evaluation of regional cardiac function, especially in the septum of patients with CABG. METHODS: Before and 3 to 5 wk after CABG (all patients underwent at least 1 bypass grafting to the left anterior descending coronary artery), 35 patients (28 men, 7 women) underwent gated SPECT using (99m)Tc-methoxyisobutylisonitrile. Quantitative global and regional ventricular functional analysis was performed using quantitative gated SPECT software. RESULTS: Global ejection fraction did not change (59.3% +/- 16.0% to 60.5% +/- 14.5%, P = 0.24). However, end-diastolic and end-systolic volumes lessened significantly after CABG (81.4 +/- 37.3 mL to 68.9 +/- 28.9 mL, P < 0.0001, and 38.1 +/- 33.1 mL to 30.4 +/- 23.0 mL, P < 0.005, respectively). As global function parameters, the changes in both total WM (r = 0.88) and WT (r = 0.86) correlated well with the change in ejection fraction after surgery. Segmental analysis showed a significant postoperative increase in relative tracer uptake in the anterior, anteroseptal, inferoseptal, and inferior walls and in the apex. Segmental wall motion (WM) deteriorated in the anteroseptal, inferoseptal, and mid anterior walls. On the other hand, anterolateral, inferolateral, and inferior WM increased. As a whole, these WM changes showed a reduction in septal motion associated with a concomitant increase in lateral motion after surgery. Segmental wall thickening, however, did not decrease in septal areas and did not increase in the lateral wall and correlated with percentage tracer uptake (r = 0.69) better than WM did (r = 0.30) after CABG. CONCLUSION: In patients with CABG, postoperative WM analysis by gated SPECT underestimated septal motion and overestimated lateral motion because of exaggerated systolic anteromedial cardiac translation. Therefore, wall thickening analysis would be recommended for the evaluation of postoperative cardiac function.