First validation of myocardial flow reserve assessed by dynamic <Superscript>99m</Superscript>Tc-sestamibi CZT-SPECT camera: head to head comparison with <Superscript>15</Superscript>O-water PET and fractional flow reserve in patients with suspected coronary artery disease. The WATERDAY study

Purpose

We assessed the feasibility of myocardial blood flow (MBF) and flow reserve (MFR) estimation using dynamic SPECT with a novel CZT camera in patients with stable CAD, in comparison with ¹⁵O–water PET and fractional flow reserve (FFR).

Methods

Thirty patients were prospectively included and underwent FFR measurements in the main coronary arteries (LAD, LCx, RCA). A stenosis ≥50% was considered obstructive and a FFR abnormal if ≤0.8. All patients underwent a dynamic rest/stress ^99mTc-sestamibi CZT-SPECT and ¹⁵O–water PET for MBF and MFR calculation. Net retention kinetic modeling was applied to SPECT data to estimate global uptake values, and MBF was derived using Leppo correction. Ischemia by PET and CZT-SPECT was considered present if MFR was lower than 2 and 2.1, respectively.

Results

CZT-SPECT yielded higher stress and rest MBF compared to PET for global and LAD and LCx territories, but not in RCA territory. MFR was similar in global and each vessel territory for both modalities. The sensitivity, specificity, accuracy, positive and negative predictive value of CZT-SPECT were, respectively, 83.3, 95.8, 93.3, 100 and 85.7% for the detection of ischemia and 58.3, 84.6, 81.1, 36.8 and 93% for the detection of hemodynamically significant stenosis (FFR?≤?0.8).

Conclusions

Dynamic ^99mTc-sestamibi CZT-SPECT was technically feasible and provided similar MFR compared to ¹⁵O–water PET and high diagnostic value for detecting impaired MFR and abnormal FFR in patients with stable CAD.

     

Optimization of temporal sampling for <Superscript>82</Superscript>rubidium PET myocardial blood flow quantification

Background

Suboptimal temporal sampling of left ventricular (LV) blood pool and tissue time-activity curves (TACs) may introduce bias and increased variability in estimates of myocardial blood flow (MBF) and flow reserve (MFR) from dynamic PET myocardial perfusion images. We aimed to optimize temporal sampling for estimation of MBF and MFR.

Methods

Twenty-four normal volunteers and 32 patients underwent dynamic stress/rest rubidium-82 chloride (⁸²Rb) PET imaging. Fine temporal sampling was used to estimate the full width at half maximum (FWHM) of the LV blood pool TAC. Fourier analysis was used to determine the longest sampling interval, T _S, as a function of FWHM, which preserved the information content of the blood phase. Dynamic datasets were reconstructed with frame durations varying from 2 to 20 seconds over the first 2 minutes for the blood phase and 30 to 120 seconds for the tissue phase. The LV blood pool and tissue TACs were sampled using regions of interest (ROI) and fit to a compartment model for quantification of MBF and MFR. The effects of temporal sampling on MBF and MFR were evaluated using clinical data and simulations.

Results

T _S increased linearly with input function FWHM (R = 0.93). Increasing the blood phase frame duration from 5 to 15 seconds resulted in MBF and MFR biases of 6-12% and increased variability of 14-24%. Frame durations <5 seconds had biases of less than 5% for both MBF and MFR values. Increasing the tissue phase frame durations from 30 to 120 seconds resulted in <5% biases.

Conclusions

A two-phase framing of dynamic ⁸²Rb PET images with frame durations of 5 seconds (blood phase) and 120 seconds (tissue phase) optimally samples the blood pool TAC for modern 3D PET systems.

     

Quantification of myocardial blood flow with <Superscript>82</Superscript>Rb positron emission tomography: clinical validation with <Superscript>15</Superscript>O-water

Purpose

Quantification of myocardial blood flow (MBF) with generator-produced ⁸²Rb is an attractive alternative for centres without an on-site cyclotron. Our aim was to validate ⁸²Rb-measured MBF in relation to that measured using ¹⁵O-water, as a tracer 100% of which can be extracted from the circulation even at high flow rates, in healthy control subject and patients with mild coronary artery disease (CAD).

Methods

MBF was measured at rest and during adenosine-induced hyperaemia with ⁸²Rb and ¹⁵O-water PET in 33 participants (22 control subjects, aged 30?±?13 years; 11 CAD patients without transmural infarction, aged 60?±?13 years). A one-tissue compartment ⁸²Rb model with ventricular spillover correction was used. The ⁸²Rb flow-dependent extraction rate was derived from ¹⁵O-water measurements in a subset of 11 control subjects. Myocardial flow reserve (MFR) was defined as the hyperaemic/rest MBF. Pearson’s correlation r, Bland-Altman 95% limits of agreement (LoA), and Lin’s concordance correlation ρ _c (measuring both precision and accuracy) were used.

Results

Over the entire MBF range (0.66–4.7 ml/min/g), concordance was excellent for MBF (r?=?0.90, [⁸²Rb–¹⁵O-water] mean difference?±?SD?=?0.04?±?0.66 ml/min/g, LoA?=??1.26 to 1.33 ml/min/g, ρ _c?=?0.88) and MFR (range 1.79–5.81, r?=?0.83, mean difference?=?0.14?±?0.58, LoA?=??0.99 to 1.28, ρ _c?=?0.82). Hyperaemic MBF was reduced in CAD patients compared with the subset of 11 control subjects (2.53?±?0.74 vs. 3.62?±?0.68 ml/min/g, p?=?0.002, for ¹⁵O-water; 2.53?±?1.01 vs. 3.82?±?1.21 ml/min/g, p?=?0.013, for ⁸²Rb) and this was paralleled by a lower MFR (2.65?±?0.62 vs. 3.79?±?0.98, p?=?0.004, for ¹⁵O-water; 2.85?±?0.91 vs. 3.88?±?0.91, p?=?0.012, for ⁸²Rb). Myocardial perfusion was homogeneous in 1,114 of 1,122 segments (99.3%) and there were no differences in MBF among the coronary artery territories (p?>?0.31).

Conclusion

Quantification of MBF with ⁸²Rb with a newly derived correction for the nonlinear extraction function was validated against MBF measured using ¹⁵O-water in control subjects and patients with mild CAD, where it was found to be accurate at high flow rates. ⁸²Rb-derived MBF estimates seem robust for clinical research, advancing a step further towards its implementation in clinical routine.

     

Usefulness of SPECT/CT in Parathyroid Lesion Detection in Patients with Thyroid Parenchymal <Superscript>99m</Superscript>Tc-Sestamibi Retention

Purpose

Parathyroid adenoma detection with dual-phase ^99mTc-sestamibi (MIBI) scintigraphy depends on differential MIBI washout from thyroid. However, autoimmune thyroid disease (AITD) may cause MIBI to be retained in the thyroid gland and reduce parathyroid detection. We evaluated the impact of AITD on MIBI thyroid retention and additional benefit of SPECT/CT in these patients.

Methods

Dual phase planar MIBI and SPECT/CT was performed on 82 patients. SPECT/CT was performed immediately after delayed planar scan. Thyroid density (Hounsfield unit, CT-HU) and size were measured on CT component of SPECT/CT. MIBI uptake in early scans and retention in delayed scans were visually graded and correlated with clinical factors and CT findings. Finally, planar and SPECT/CT findings were compared for parathyroid lesion visualization according to thyroid MIBI retention.

Results

In early scan, multivariate analysis showed only thyroid size predicted early uptake. In delayed scan, multivariate analysis showed higher visual grade in early scan, lower CT-HU or AITD were significant predictors for delayed thyroid parenchymal retention. Overall, ten more parathyroid lesions were visualized on SPECT/CT compared to planar scans (57 vs. 47, p?=?0.002). SPECT/CT was especially more useful in patients with thyroidal MIBI retention, as eight out of the ten additional lesions detected were found in patients with thyroid MIBI retention.

Conclusion

AITD is an important factor for MIBI thyroid parenchymal retention on delayed scans, and may impede parathyroid lesion detection. Patients with MIBI retention in the thyroid parenchyma on delayed scans are likely to benefit from an additional SPECT/CT.

     

Relationships between left ventricular asynchrony and myocardial blood flow

Objective

⁸²Rb PET protocols enable determination of left ventricular asynchrony (LVAS) at rest and stress, along with myocardial blood flow (MBF). We hypothesized that in patients with resting LVAS, MBF differs between those with stress-induced LVAS improvement and those with stress-induced LVAS deterioration.

Methods

We retrospectively analyzed ⁸²Rb rest/regadenoson stress PET studies of 195 patients evaluated for known or suspected coronary artery disease. MBF was computed from first-pass data; function and relative perfusion were computed from myocardial equilibrium data. LVAS was defined as phase contraction bandwidth (BW) above ⁸²Rb gender-specific normal limits, with changes defined as BW moving into or out of normal ranges.

Results

Among the 195 patients, 64 had LVAS at rest, of whom 13 reverted to normal and 51 continued to have LVAS with stress. Patients who did not improve had lower stress MBF (1.04 ± 0.69 vs 1.58 ± 0.67, p = .02) and coronary flow reserve (1.94 ± 1.16 vs 3.04 ± 1.22, p = .01) than those who did improve. ROC analysis indicated that the parameter most strongly associated with improvement in asynchrony for patients with resting LVAS was reduction in MBF heterogeneity (ROC area (accuracy) = 84%, sensitivity = 92%, and specificity = 67%).

Conclusion

LVAS is highly correlated with MBF and CVR, with stress-induced improvement in synchronicity most strongly associated with improved MBF homogeneity.

     

Compared to <Superscript>123</Superscript>I-MIBG SPECT/CT, <Superscript>18</Superscript>F-DOPA PET/CT provides accurate tumor extent in patients with extra-adrenal paraganglioma

Aim

The aim of this study was to compare the accuracy of ¹²³I-MIBG SPECT/CT with that of ¹⁸F-DOPA PET/CT for staging extra-adrenal paragangliomas (PGLs) using both functional and anatomical images (i.e., combined cross-sectional imaging) as the reference standards.

Methods

Three men and seven women (age range 26–73 years) with anatomical and/or histologically proven disease were included in this study. Three patients had either metastatic head-and-neck paragangliomas (HNPGLs) or multifocal PGL, and seven patients had nonmetastatic disease. Comparative evaluation included morphological imaging with CT, functional imaging with ¹⁸F-DOPA PET, and ¹²³I-MIBG imaging including SPECT/CT. Imaging results were analyzed on a per-patient and per-lesion basis.

Results

On a per-patient basis, ¹⁸F-DOPA PET’s detection rate for both nonmetastatic and metastatic/multifocal disease was 100%, whereas that of planar ¹²³I-MIBG imaging alone was 10.0% and that of ¹²³I-MIBG SPECT/CT was 20.0%. Overall, on a per-lesion basis, ¹⁸F-DOPA PET showed a sensitivity of 69.2% (McNemar p?<?0.001) compared with anatomical imaging. Sensitivity of planar ¹²³I-MIBG scintigraphy was 5.6%, and that of SPECT/CT was 11.1% (McNemar p?<?0.0001). Overall, ¹⁸F-DOPA PET identified 18 lesions, and anatomical imaging identified 26 lesions; planar ¹²³IMIBG imaging identified only 1 lesion, and SPECT/CT, 2 lesions.

Conclusion

¹⁸F-DOPA PET is more sensitive than is ¹²³I-MIBG imaging, including SPECT/CT, for staging HNPGL. Combined functional and anatomical imaging (PET/CT) is indicated to exclude metastatic disease in extra-adrenal PGL.

     

Myocardial blood flow and left ventricular functional reserve in hypertrophic cardiomyopathy: a <Superscript>13</Superscript>NH<Subscript>3</Subscript> gated PET study

Introduction

Ischemia in hypertrophic cardiomyopathy (HCM) is caused by coronary microvascular dysfunction (CMD), which is detected by measuring myocardial blood flow (MBF) with PET. Whether CMD may be associated with ischemic left ventricular (LV) dysfunction is unclear. We therefore assessed LV ejection fraction (EF) reserve in HCM patients undergoing dipyridamole (Dip) PET.

Methods

Resting and stress ¹³NH₃ dynamic as well as gated PET were performed in 34 HCM patients. Segmental MBF and transmural perfusion gradient (TPG?=?subendocardial / subepicardial MBF) were assessed. LVEF reserve was considered abnormal if Dip LVEF decreased more than 5 units as compared to rest.

Results

Eighteen patients had preserved (group A) and 16 abnormal LVEF reserve (group B; range ?7 to ?32). Group B patients had greater wall thickness than group A, but resting volumes, LVEF, resting and Dip MBF, and myocardial flow reserve were similar. Group B had slightly higher summed stress score and summed difference score in visual analysis than group A, and a significantly higher summed stress wall motion score. In group B, resting TPG was slightly lower (1.31?±?0.29 vs. 1.37?±?0.34, p <0.05), and further decreased after Dip, whilst in group A it increased (B?=?1.20?±?0.39, p?<?0.0001 vs. rest and vs. A?=?1.40?±?0.43). The number of segments per patient with TPG <1 was higher than in group A (p?<?0.001) and was a significant predictor of impaired LVEF reserve (OR 1.86, p?<?0.02), together with wall thickness (OR 1.3, p?<?0.02).

Conclusion

Abnormal LVEF response is common in HCM patients following Dip, and is related to abnormal TPG, suggesting that subendocardial ischemia might occur under Dip and cause transient LV dysfunction. Although in vivo this effect may be hindered by the adrenergic drive associated with effort, these findings may have relevance in understanding exercise limitation and heart failure symptoms in HCM.

     

Stress myocardial blood flow correlates with ventricular function and synchrony better than myocardial perfusion reserve: A Nitrogen-13 ammonia PET study

Background

Cardiac PET quantifies stress myocardial blood flow (MBF) and perfusion reserve (MPR), while ECG-gated datasets can measure components of ventricular function simultaneously. Stress MBF seems to outperform MPR in the detection of significant CAD. However, it is uncertain which perfusion measurement is more related to ventricular function. We hypothesized that stress MBF correlates with ventricular function better than MPR in patients studied for suspected myocardial ischemia.

Methods

We studied 248 patients referred to a rest and adenosine-stress Nitrogen-13 ammonia PET. We performed a multivariate analysis using systolic function (left ventricular ejection fraction, LVEF), diastolic function (mean filling rate in diastole, MFR/3), and synchrony (Entropy) as the outcome variables, and stress MBF, MPR, and relevant covariates as the predictors. Secondarily, we repeated the analysis for the subgroup of patients with and without a previous myocardial infarction (MI).

Results

166 male and 82 female patients (mean age 63 ± 11 and 67 ± 11 year, respectively) were included. 60% of the patients presented hypertension, 57% dyslipidemia, 21% type 2 diabetes mellitus, 45% smoking, and 34.7% a previous MI. Mean stress MBF was 1.99 ± 0.75 mL/g/min, MPR = 2.55 ± 0.89, LVEF = 61.6 ± 15%, MFR/3 = 1.12 ± 0.38 EDV/s, and Entropy = 45.6 ± 11.3%. There was a significant correlation between stress MBF (P < .001) and ventricular function. This was stronger than the one for MPR (P = .063). Sex, age, diabetes, and extent of previous MI were also significant predictors. Results were similar for the analyses of the 2 subgroups.

Conclusion

Stress MBF is better correlated with ventricular function than MPR, as evaluated by Nitrogen-13 ammonia PET, independently from other relevant cardiovascular risk factors and clinical covariates. This relationship between coronary vasodilatory capacity and ventricular function is sustained across groups with and without a previous MI.

     

Combined evaluation of regional coronary artery calcium and myocardial perfusion by <Superscript>82</Superscript>Rb PET/CT in the identification of obstructive coronary artery disease

Purpose

Cardiac imaging with PET/CT allows measurement of coronary artery calcium (CAC), myocardial perfusion and coronary vascular function. We investigated whether the combined assessment of regional CAC score, ischemic total perfusion deficit (ITPD) and quantitative coronary vascular function would further improve the diagnostic accuracy of PET/CT in predicting obstructive coronary artery disease (CAD).

Methods

We analyzed 113 patients with suspected CAD referred to ⁸²Rb PET/CT myocardial perfusion imaging with available coronary angiographic data. Obstructive CAD was defined as ≥75% stenosis. The receiver operating characteristic area under curve (AUC) was applied to evaluate the ability of CAC score, ITPD, hyperemic myocardial blood flow (MBF) and coronary flow reserve (CFR) to identify CAD.

Results

Vessels with obstructive CAD (71 vessels) had higher ITPD (4.6?±?6.2 vs. 0.6?±?1.3) and lower hyperemic MBF (1.01?±?0.5 vs. 1.75?±?0.6 ml/min/g) and CFR (1.56?±?0.6 vs. 2.38?±?0.7; all p?<?0.001) than those without. In prediction of per-vessel CAD, the AUCs for the models including CAC/ITPD/hyperemic MBF (0.869) and CAC/ITPD/CFR (0.875) were higher (both p?<?0.01) than for the model including CAC/ITPD (0.790). Compared with CAC/ITPD, continuous net reclassification improvement was 0.69 (95% bootstrap confidence interval, CI, 0.365–1.088) for the CAC/ITPD/hyperemic MBF model and 0.99 (95% bootstrap CI 0.64–1.26) for the CAC/ITPD/CFR model.

Conclusion

Hyperemic MBF and CFR provide incremental information about the presence of CAD over CAC score and perfusion imaging parameters. The combined use of CAC, myocardial perfusion imaging and quantitative coronary vascular function in may help predict more accurately the presence of obstructive CAD.

     

<Superscript>68</Superscript>Ga-DOTATATE PET/CT in recurrent medullary thyroid carcinoma: a lesion-by-lesion comparison with <Superscript>111</Superscript>In-octreotide SPECT/CT and conventional imaging

Purpose

The aim of this study was to prospectively compare the detection rate of ⁶⁸Ga-DOTATATE PET-CT with ¹¹¹In-octreotide SPECT-CT and conventional imaging (CI) in medullary thyroid carcinoma (MTC) patients with increased calcitonin (Ctn) levels but negative CI after thyroidectomy.

Methods

Fifteen patients with raised Ctn levels and/or CI evidence of recurrence underwent ⁶⁸Ga-DOTATATE PET-CT, ¹¹¹In-octreotide SPECT-CT and CI. Histopathology, CI and biochemical/clinical/imaging follow-up were used as the reference standard. PET/CT, SPECT/CT and CI were compared in a lesion-based and organ-based analysis.

Results

PET/CT evidenced recurrence in 14 of 15 patients. There were 13 true positive (TP), 1 true negative (TN), 1 false positive (FP) and no false negative (FN) cases, resulting in a sensitivity and accuracy of 100% and 93%. SPECT/CT was positive in 6 of 15 cases. There were 6 TP, 2 TN, 7 FN and no FP cases, resulting in a sensitivity of 46% and accuracy of 53%. CI procedures detected tumor lesions in 14 of 15 patients. There were 13 TP, 1TN, 1 FP and no FN cases with a sensitivity of 100% and accuracy of 93%.A significantly higher number of lesions was detected by PET/CT (112 lesions, p = 0.005) and CI (109 lesions, p = 0.005) in comparison to SPECT/CT (16 lesions). There was no significant difference between PET/CT and CI for the total number of detected lesions (p = 0.734). PET/CT detected more lesions than SPECT/CT regardless of the organ. PET/CT detected more bone lesions but missed some neck nodal metastases evidenced by CI. The number of lesions per region demonstrated by PET/CT and CI were similar in the other sites.

Conclusion

⁶⁸Ga-DOTATATE PET/CT is superior to ¹¹¹In-octreotide SPECT/CT for the detection of recurrent MTC demonstrating a significantly higher number of lesions. ⁶⁸Ga-DOTATATE PET/CT showed a superior detection rate compared to CI in demonstrating bone metastases.

     

Single-scan rest/stress imaging: validation in a porcine model with <Superscript>18</Superscript>F-Flurpiridaz

Purpose

¹⁸F-labeled myocardial flow agents are becoming available for clinical application but the ～2 hour half-life of ¹⁸F complicates their clinical application for rest-stress measurements. The goal of this work is to evaluate in a pig model a single-scan method which provides quantitative rest-stress blood flow in less than 15 minutes.

Methods

Single-scan rest-stress measurements were made using ¹⁸F-Flurpiridaz. Nine scans were performed in healthy pigs and seven scans were performed in injured pigs. A two-injection, single-scan protocol was used in which an adenosine infusion was started 4 minutes after the first injection of ¹⁸F-Flurpiridaz and followed either 3 or 6 minutes later by a second radiotracer injection. In two pigs, microsphere flow measurements were made at rest and during stress. Dynamic images were reoriented into the short axis view, and regions of interest (ROIs) for the 17 myocardial segments were defined in bull’s eye fashion. PET data were fitted with MGH2, a kinetic model with time varying kinetic parameters, in which blood flow changes abruptly with the introduction of adenosine. Rest and stress myocardial blood flow (MBF) were estimated simultaneously.

Results

The first 12–14 minutes of rest-stress PET data were fitted in detail by the MGH2 model, yielding MBF measurement with a mean precision of 0.035 ml/min/cc. Mean myocardial blood flow across pigs was 0.61?±?0.11 mL/min/cc at rest and 1.06?±?0.19 mL/min/cc at stress in healthy pigs and 0.36?±?0.20 mL/min/cc at rest and 0.62?±?0.24 mL/min/cc at stress in the ischemic area. Good agreement was obtained with microsphere flow measurement (slope?=?1.061?±?0.017, intercept?=?0.051?±?0.017, mean difference 0.096?±?0.18 ml/min/cc).

Conclusion

Accurate rest and stress blood flow estimation can be obtained in less than 15 min of PET acquisition. The method is practical and easy to implement suggesting the possibility of clinical translation.

     

Repeatable and reproducible measurements of myocardial oxidative metabolism,blood flow and external efficiency using <Superscript>11</Superscript>C-acetate PET

Background

Non-invasive approaches to investigate myocardial efficiency can help track the progression of heart failure (HF). This study evaluates the repeatability and reproducibility of ¹¹C-acetate positron emission tomography (PET) imaging of oxidative metabolism.

Methods and results

Dynamic ¹¹C-acetate PET scans were performed at baseline and followup (47 ± 22 days apart) in 20 patients with stable HF with reduced ejection fraction. Two observers blinded to patients’ clinical data used FlowQuant^® to evaluate test–retest repeatability, as well as intra- and inter-observer reproducibility of ¹¹C-acetate tracer uptake and clearance rates, for the measurement of myocardial oxygen consumption (MVO₂), myocardial external efficiency (MEE), work metabolic index (WMI), and myocardial blood flow. Reproducibility and repeatability were evaluated using intra-class-correlation (ICC) and Bland–Altman coefficient-of-repeatability (CR). Test–retest correlations and repeatability were better for MEE and WMI compared to MVO₂. All intra- and inter-observer correlations were excellent (ICC = 0.95-0.99) and the reproducibility values (CR = 3%-6%) were significantly lower than the test–retest repeatability values (22%-54%, P < 0.001). Repeatability was improved for all parameters using a newer PET–computed tomography (CT) scanner compared to older PET-only instrumentation.

Conclusion

¹¹C-acetate PET measurements of WMI and MEE exhibited excellent test–retest repeatability and operator reproducibility. Newer PET–CT scanners may be preferred for longitudinal tracking of cardiac efficiency.

     

Relationship between collateral circulation and myocardial viability of <Superscript>18</Superscript>F-FDG PET/CT subtended by chronic total occluded coronary arteries

Objective

To analyze the relationship between the collateral flow of coronary chronic total occlusion (CTO) and myocardial viability detected by ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) imaging.

Methods

A prospective analysis of 104 patients diagnosed by coronary angiography. All patients underwent resting myocardial perfusion imaging and PET/CT within 1 week. The collateral circulation was graded with Rentrop classification as no or poor collateral circulation in 16 CTO vessels, moderate collateral circulation in 34 CTO vessels, and good collateral circulation in 69 CTO vessels. Myocardial viability was determined with myocardial perfusion imaging and PET. The patterns were interpreted as mismatch, match and normal perfusion and ¹⁸F-FDG uptake.

Results

There was no significant correlation between the severity and extent of perfusion defect, myocardial viability and collateral circulation grade. The myocardial viability was normal in mild and moderate hypokinetic regions and decreased in severe hypokinetic and akinesis–dyskinesis regions. The presence of collateral circulation was a sensitive (89%) but not a specific (31%) sign of myocardial viability.

Conclusions

In patients with CTO, collateral circulation does not seem to be an effective way for predicting myocardial viability. Further analysis of PET patterns of viable myocardium is needed to guide further revascularization and predict functional improvement and survival benefit.

     

<Superscript>68</Superscript>Ga-PSMA-HBED-CC PET imaging in breast carcinoma patients

Background

To report on imaging findings using ⁶⁸Ga-PSMA-HBED-CC PET in a series of 19 breast carcinoma patients.

Methods

⁶⁸Ga-PSMA-HBED-CC PET imaging results obtained were compared to routinely performed staging examinations and analyzed as to lesion location and progesterone receptor status.

Results

Out of 81 tumor lesions identified, 84% were identified on ⁶⁸Ga-PSMA-HBED-CC PET. ⁶⁸Ga-PSMA-HBED-CC SUVmean values of distant metastases proved significantly higher (mean, 6.86, SD, 5.68) when compared to those of primary or local recurrences (mean, 2.45, SD, 2.55, p?=?0.04) or involved lymph nodes (mean, 3.18, SD, 1.79, p?=?0.011). SUVmean values of progesterone receptor-positive lesions proved not significantly different from progesterone receptor-negative lesions. SUV values derived from FDG PET/CT, available in seven patients, and ⁶⁸Ga-PSMA-HBED-CC PET/CT imaging proved weakly correlated (r?=?0.407, p?=?0.015).

Conclusions

⁶⁸Ga-PSMA-HBED-CC PET/CT imaging in breast carcinoma confirms the reported considerable variation of PSMA expression on human solid tumors using immunohistochemistry.

     

Utility of <Superscript>18</Superscript>F-fluoroestradiol (<Superscript>18</Superscript>F-FES) PET/CT imaging as a pharmacodynamic marker in patients with refractory estrogen receptor-positive solid tumors receiving Z-endoxifen therapy

Background

Z-endoxifen is the most potent of the metabolites of tamoxifen, and has the potential to be more effective than tamoxifen because it bypasses potential drug resistance mechanisms attributable to patient variability in the expression of the hepatic microsomal enzyme CYP2D6. ¹⁸F-FES is a positron emission tomography (PET) imaging agent which selectively binds to estrogen receptor alpha (ER-α) and has been used for non-invasive in vivo assessment of ER activity in tumors. This study utilizes ¹⁸F-FES PET imaging as a pharmacodynamic biomarker in patients with ER+ tumors treated with Z-endoxifen.

Methods

Fifteen patients were recruited from a parent therapeutic trial of Z-endoxifen and underwent imaging with ¹⁸F-FES PET at baseline. Eight had positive lesions on the baseline scan and underwent follow-up imaging with ¹⁸F-FES 1–5 days post administration of Z-endoxifen.

Results

Statistically significant changes (p?=?0.0078) in standard uptake value (SUV)-Max were observed between the baseline and follow-up scans as early as 1 day post drug administration.

Conclusion

F-FES PET imaging could serve as a pharmacodynamic biomarker for patients treated with ER-directed therapy.

     

Molecular response assessed by <Superscript>68</Superscript>Ga-DOTANOC and survival after <Superscript>90</Superscript>Y microsphere therapy in patients with liver metastases from neuroendocrine tumours

Purpose

We investigated the prognostic role of ⁶⁸Ga-DOTANOC in patients affected by hepatic metastases from neuroendocrine tumours (NET) undergoing ⁹⁰Y radioembolization (⁹⁰Y-RE).

Methods

A group of 15 consecutive patients with unresectable NET liver metastases underwent ⁶⁸Ga-DOTANOC PET at baseline and 6 weeks after ⁹⁰Y-RE. Molecular response was defined as a reduction of >50 % in the tumour-to-spleen ratio (ΔT/S). The patients were divided into two groups (responders with ΔT/S >50 % and nonresponders with ΔT/S <50 %) Patients were followed up by imaging and laboratory tests every 3 months until death or for at least 36 months following ⁹⁰Y-RE. Statistical analysis was performed to identify factors predicting overall survival (OS) and progression-free survival (PFS).

Results

A decrease in T/S ratio was seen in all patients on ⁶⁸Ga-DOTANOC PET scans performed after ⁹⁰Y-RE. Nine patients were classified as responders and six as nonresponders. The mean OS in all patients was 31.0 months. Responders had a significantly (p?<?0.001) longer OS (mean 36.0?±?2.5 months) and PFS (mean 29.7?±?3.4 months) than nonresponders. In a multivariate analysis, none of the other examined variables including age, unilobar vs. bilobar locations, bilirubin levels, radiological response or the presence of extrahepatic disease significantly predicted patient outcome.

Conclusion

Molecular response assessed with ⁶⁸Ga-DOTANOC PET might be a useful predictor of survival in patients affected by NET liver metastases treated with ⁹⁰Y-RE.

     

Comparison of bone scintigraphy and <Superscript>68</Superscript>Ga-PSMA PET for skeletal staging in prostate cancer

Purpose

The aim of our study was to compare the diagnostic performance of ⁶⁸Ga-PSMA PET and ^99mTc bone scintigraphy (BS) for the detection of bone metastases in prostate cancer (PC) patients.

Methods

One hundred twenty-six patients who received planar BS and PSMA PET within three months and without change of therapy were extracted from our database. Bone lesions were categorized into benign, metastatic, or equivocal by two experienced observers. A best valuable comparator (BVC) was defined based on BS, PET, additional imaging, and follow-up data. The cohort was further divided into clinical subgroups (primary staging, biochemical recurrence, and metastatic castration-resistant prostate cancer [mCRPC]). Additionally, subgroups of patients with less than 30 days delay between the two imaging procedures and with additional single-photon emission computed tomography (SPECT) were analyzed.

Results

A total of 75 of 126 patients were diagnosed with bone metastases. Sensitivities and specificities regarding overall bone involvement were 98.7–100 % and 88.2–100 % for PET, and 86.7–89.3 % and 60.8–96.1 % (p?<?0.001) for BS, with ranges representing results for ‘optimistic’ or ‘pessimistic’ classification of equivocal lesions. Out of 1115 examined bone regions, 410 showed metastases. Region-based analysis revealed a sensitivity and specificity of 98.8–99.0 % and 98.9–100 % for PET, and 82.4–86.6 % and 91.6–97.9 % (p?<?0.001) for BS, respectively. PSMA PET also performed better in all subgroups, except patient-based analysis in mCRPC.

Conclusion

Ga-PSMA PET outperforms planar BS for the detection of affected bone regions as well as determination of overall bone involvement in PC patients. Our results indicate that BS in patients who have received PSMA PET for staging only rarely offers additional information; however, prospective studies, including a standardized integrated x-ray computed tomography (SPECT/CT) protocol, should be performed in order to confirm the presented results.

     

Molecular imaging of cholinergic processes in prostate cancer using <Superscript>11</Superscript>C-donepezil and <Superscript>18</Superscript>F-FEOBV

Purpose

High-grade prostate cancer (PC) displays parasympathetic neoneurogenesis. We investigated the binding of two PET tracers that visualize cholinergic nerves in PC tissue using autoradiography.

Methods

Prostatectomy tissue was subjected to autoradiography with ¹¹C-donepezil and ¹⁸F-FEOBV and correlated with Gleason scores (GS). Regions of interest on the autoradiograms were defined and quantified. Tracer binding in cancer tissue regions was compared with that in normal tissue.

Results

We included 13 patients with biopsy-verified PC. In particular, ¹¹C-donepezil uptake was higher in “high-grade” PC (GS ≥4?+?3) than in “low-grade” PC and benign hyperplasia. ¹¹C-donepezil uptake ranged from a mean of 56 % higher (GS 3?+?3) to 409 % higher (GS 4?+?4), and ¹⁸F-FEOBV uptake ranged from 67 % higher (GS 3?+?3) to 194 % higher (GS 4?+?5). The uptake of both tracers was higher in PC with a high GS than in PC with a low GS, but the difference was significant only for ¹¹C-donepezil (p?=?0.003).

Conclusion

Uptake of PET tracers binding to cholinergic nerves was markedly higher in PC with a high GS than in PC with a low GS. This finding implies that ¹¹C-donepezil PET/CT may be able to differentiate between low-grade and high-grade PC.

     

Diagnostic performance and impact on patient management of <Superscript>68</Superscript>Ga-DOTA-TOC PET/CT for detecting osteomalacia-associated tumours

Purpose

Oncogenic osteomalacia is an endocrine disorder induced by small benign tumours (TIO) producing excessive fibroblast growth factor-23 (FGF23). The only way of curing oncogenic osteomalacia is surgical resection of the culprit TIO, which is extremely difficult to detect using conventional imaging modalities due to its small size and variable location in the body. Since TIO frequently overexpress somatostatin receptors, a clinical utility of SPECT or PET with radiolabelled somatostatin analogues has been reported. Among them, ⁶⁸Ga-DOTA-TOC has recently been granted a marketing authorization, facilitating its routine application. We report here the results of the first series evaluating the diagnostic performance of ⁶⁸Ga-DOTA-TOC PET/CT in detecting TIO and its impact on patient management.

Methods

⁶⁸Ga-DOTA-TOC PET/CT and clinical and imaging data from 15 patients with clinical and biochemical signs of oncogenic osteomalacia were retrospectively reviewed. The ⁶⁸Ga-DOTA-TOC PET/CT findings were compared with the results of post-surgical pathology and clinical and biochemical follow-up.

Results

⁶⁸Ga-DOTA-TOC PET/CT resulted in the detection of one focus suspicious for TIO in nine of 15 patients (60%), and a tumour was surgically removed in eight. Post-operative pathology confirmed a TIO in those eight patients whose symptoms diminished promptly and biochemical anomalies resolved. ⁶⁸Ga-DOTA-TOC PET/CT sensitivity, specificity and accuracy were 73%, 67% and 71%, respectively. ⁶⁸Ga-DOTA-TOC PET/CT findings affected patient management in 67% of cases. In particular, ⁶⁸Ga-DOTA-TOC PET/CT was able to detect the TIO with a negative or a false-positive result of a previous ¹¹¹In-pentetreotide SPECT/CT in 5/8 patients (63%) or a previous FDG PET/CT in 7/11 patients (64%). No close relationship was found between the positivity of ⁶⁸Ga-DOTA-TOC PET/CT and the serum level of a biochemical marker. However, a true-positive result of ⁶⁸Ga-DOTA-TOC PET/CT was obtained in only one patient with a non-elevated serum level of FGF23.

Conclusion

⁶⁸Ga-DOTA-TOC PET/CT is an accurate imaging modality in the detection of TIO; in particular, it is worthwhile after failure of somatostatin receptor SPECT(/CT) or FDG PET/CT.

     

<Superscript>18</Superscript>F-FDG uptake by rectal cancer is similar in mucinous and nonmucinous histological subtypes

Purpose

PET/CT has been considered limited for the evaluation of mucinous colorectal tumors due to low ¹⁸F-FDG uptake. The aim of our study was to compare PET/CT variables in mucinous (MC) and nonmucinous (NMC) rectal adenocarcinomas.

Methods

Consecutive patients with cT2-4N0-2M0 rectal cancer included in a prospective clinical trial were reviewed. PET/CT was performed for primary baseline staging. Visual and quantitative analysis included SUVmax and SUVmean, metabolic tumor volume (MTV) and total lesion glycolysis (TLG). PET/CT parameters were compared according to histological subtypes.

Results

Overall, 73 patients were included (18 mucinous and 55 nonmucinous). SUVmax values were similar between MC and NMC (19.7 vs. 16.6; p = 0.5). MTV and TLG values were greater in the MC group (103.9 vs. 54.1; p = 0.007 and 892.5 vs. 358.8; p = 0.020) due to larger tumor volumes of MC.

Conclusions

Metabolic parameters at baseline PET/CT for patients with rectal cancer are similar in mucinous and nonmucinous histological subtypes.