89Zr-Trastuzumab PET/CT Imaging of HER2-Positive Breast Cancer for Predicting Pathological Complete Response after Neoadjuvant Systemic Therapy: A Feasibility Study.

BACKGROUND: Approximately 20% of invasive ductal breast malignancies are human epidermal growth factor receptor 2 (HER2)-positive. These patients receive neoadjuvant systemic therapy (NAT) including HER2-targeting therapies. Up to 65% of patients achieve a pathological complete response (pCR). These patients might not have needed surgery. However, accurate preoperative identification of a pCR remains challenging. A radiologic complete response (rCR) on MRI corresponds to a pCR in only 73% of patients. The current feasibility study investigates if HER2-targeted PET/CT-imaging using Zirconium-89 (89Zr)-radiolabeled trastuzumab can be used for more accurate NAT response evaluation. METHODS: HER2-positive breast cancer patients scheduled to undergo NAT and subsequent surgery received a 89Zr-trastuzumab PET/CT both before (PET/CT-1) and after (PET/CT-2) NAT. Qualitative and quantitative response evaluation was performed. RESULTS: Six patients were enrolled. All primary tumors could be identified on PET/CT-1. Four patients had a pCR and two a pathological partial response (pPR) in the primary tumor. Qualitative assessment of PET/CT resulted in an accuracy of 66.7%, compared to 83.3% of the standard-of-care MRI. Quantitative assessment showed a difference between the SUVR on PET/CT-1 and PET/CT-2 (ΔSUVR) in patients with a pPR and pCR of -48% and -90% (p = 0.133), respectively. The difference in tumor-to-blood ratio on PET/CT-1 and PET/CT-2 (ΔTBR) in patients with pPR and pCR was -79% and -94% (p = 0.133), respectively. Three patients had metastatic lymph nodes at diagnosis that were all identified on PET/CT-1. All three patients achieved a nodal pCR. Qualitative assessment of the lymph nodes with PET/CT resulted in an accuracy of 66.7%, compared to 50% of the MRI. CONCLUSIONS: NAT response evaluation using 89Zr-trastuzumab PET/CT is feasible. In the current study, qualitative assessment of the PET/CT images is not superior to standard-of-care MRI. Our results suggest that quantitative assessment of 89Zr-trastuzumab PET/CT has potential for a more accurate response evaluation of the primary tumor after NAT in HER2-positive breast cancer.

Intramyocardial bone marrow cell injection does not lead to functional improvement in patients with chronic ischaemic heart failure without considerable ischaemia.

BACKGROUND: It has been suggested that bone marrow cell injection may have beneficial effects in patients with chronic ischaemic heart disease. However, previous trials have led to discrepant results of cell-based therapy in patients with chronic heart failure. The aim of this study was to evaluate the efficacy of intramyocardial injection of mononuclear bone marrow cells in patients with chronic ischaemic heart failure with limited stress-inducible myocardial ischaemia. METHODS AND RESULTS: This multicentre, randomised, placebo-controlled trial included 39 patients with no-option chronic ischaemic heart failure with a follow-up of 12 months. A total of 19 patients were randomised to autologous intramyocardial bone marrow cell injection (cell group) and 20 patients received a placebo injection (placebo group). The primary endpoint was the group difference in change of left ventricular ejection fraction, as determined by single-photon emission tomography. On follow-up at 3 and 12 months, change of left ventricular ejection fraction in the cell group was comparable with change in the placebo group (P = 0.47 and P = 0.08, respectively). Also secondary endpoints, including left ventricle volumes, myocardial perfusion, functional and clinical parameters did not significantly change in the cell group as compared to placebo. Neither improvement was demonstrated in a subgroup of patients with stress-inducible ischaemia (P = 0.54 at 3­month and P = 0.15 at 12-month follow-up). CONCLUSION: Intramyocardial bone marrow cell injection does not improve cardiac function, nor functional and clinical parameters in patients with severe chronic ischaemic heart failure with limited stress-inducible ischaemia. CLINICAL TRIAL REGISTRATION: NTR2516.

Effects of heart rate, filling and slice thickness on the accuracy of left ventricular volume measurements in a dynamic cardiac phantom using ECG-gated MDCT.

The objective of the study was to assess the effect of heart rate, filling condition and slice thickness on the accuracy of volumetric analysis based on multidetector-row computed tomography (MDCT) of a cardiac phantom. Retrospective electrocardiogram-gated MDCT of a pulsating phantom was performed under different conditions. End-diastolic volume (EDV) and end-systolic volume (ESV) for different heart rates (60-75 beats per minute), filling volumes and reconstructed slice thicknesses (2 mm and 5 mm) were obtained by three observers. Results were analysed by a linear mixed-effects model. Significant effects on the accuracy were found for heart rate (F-value, 7.3-39.2; p<0.004) and filling condition (F-value, 7.4-55.6; p<0.004), but not for slice thickness. Small relative differences in the assessment of EDV were found (range, -3% to 3%), but there was a trend for overestimation of the ESV (range, -1% to 18%). Underestimation of stroke volume and ejection fraction (range, -1% to -11%) became smaller under conditions of improved temporal resolution and larger EDV. Good interobserver agreement was found (SD <1.8 ml and <0.5%). In conclusion, MDCT allows sufficient and reliable measurements of ventricular volumes and calculation of left ventricle function for clinical applications. Heart rate and filling conditions significantly affect the accuracy of volumetrics, as demonstrated in this cardiac phantom. Thicker slices provide similar accuracy to thin slices.

Assessment of regional myocardial wall motion and thickening by gated 99Tcm-tetrofosmin SPECT: a comparison with magnetic resonance imaging.

Gated single photon emission computed tomography (SPECT) imaging allows the simultaneous assessment of both perfusion and function by using one single study. The assessment of regional wall motion and thickening pattern with gated SPECT allows viability studies to be performed. Magnetic resonance imaging (MRI) is well validated for the assessment of myocardial wall motion and thickening in patients with normal and impaired ventricular function. The aim of the study was to analyse the concordance between wall motion and thickening scores derived by gated SPECT and MRI imaging. Furthermore, the agreement for myocardial wall motion and thickening according to myocardial perfusion was analysed with both techniques. We studied a group of 21 patients, including 13 with a previous myocardial infarction (all more than 4 months before the study), using both gated SPECT 99Tcm-tetrofosmin myocardial perfusion imaging and MRI. A 13-segment model was used for both gated SPECT and MRI and each segment was visually scored using a scale of 1-3 for wall motion and thickening. There was a high agreement between gated SPECT and MRI for both wall motion (229/273, 84%; k = 0.72, P<0.001) and wall thickening (236/273, 86%; k = 0.77, P<0.001). The agreement for wall motion and thickening was 80% (k = 0.66) and 83% (k = 0.70), respectively, for patients with myocardial infarction; and 90% (k = 0.81) and 92% (k = 0.86), respectively (P = NS), for patients without myocardial infarction. Agreement in segmental wall motion and thickening scores between gated SPECT and MRI was 90% (k = 0.80) and 91% (k = 0.84), respectively, for segments with normal or mild to moderate hypoperfusion; and 71% (k = 0.45) and 77% (k = 0.57), respectively, for segments with severe hypoperfusion or no perfusion. Of the 70 (41%) segments that had severely diminished or no perfusion in post-myocardial infarction patients, 22 (31%) showed preserved wall motion and 17 (24%) showed preserved wall thickening both by gated SPECT and MRI, suggesting residual myocardial viability in malperfused segments. Our results suggest that gated SPECT imaging is a reliable tool for the assessment of regional wall motion and thickening in patients with known or suspected coronary artery disease. In patients with a previous myocardial infarction gated SPECT imaging has the potential to detect preserved wall motion and thickening in regions with fixed perfusion defects indicating the potential presence of residual myocardial viability.

Detection of residual wall motion after myocardial infarction by gated technetium-99m tetrofosmin SPET: a comparison with contrast ventriculography.

The differentiation of residual viability from necrotic myocardium in patients with a prior myocardial infarction is important when deciding whether revascularization is indicated. Myocardial viability can be assessed by studying perfusion and regional wall motion. Gated single-photon emission tomography (SPET) imaging allows the simultaneous assessment of perfusion and function through a single study. The aim of this study was to analyse the concordance between wall motion score derived by gated SPET and by contrast ventriculography. Furthermore, the agreement between myocardial perfusion and regional myocardial wall motion was analysed for both techniques. We studied a homogeneous group of 26 consecutive patients with a prior myocardial infarction, using both gated technetium-99m tetrofosmin SPET and contrast ventriculography. A seven-segment model of the left ventricle was employed to score regional myocardial wall motion on images obtained with gated SPET and contrast ventriculography using a four-point scale. Contrast ventriculography was performed within 2 weeks of the gated SPET study. Prevalence of abnormal wall motion (akinetic or dyskinetic) was 24/182 (13%) for gated SPET and 25/182 (14%) for contrast ventriculography (P = NS). There was a high agreement (80%) in wall motion score between gated SPET and contrast ventriculography (kappa = 0.67, P < 0.001). The agreement was better in segments with normal or mild to moderate hypoperfusion (82%, kappa = 0.69) than in those with severe hypoperfusion (67%, kappa = 0.56). The agreement between myocardial perfusion and myocardial wall motion was 89% (162/182), kappa = 0.57, for gated SPET and 80% (145/182), kappa = 0.21, for contrast ventriculography. The relation between the summed wall motion scores per patient on gated SPET and contrast ventriculography was excellent (y = 0.81x + 2.9, r = 0.82, P < 0.01). Thirteen (43%) out of 30 segments with severely diminished or no myocardial perfusion showed normal or hypokinetic wall motion on gated SPET, suggesting residual myocardial viability in malperfused regions. Our results suggest that gated SPET imaging is a reliable tool for the assessment of regional wall motion in post-myocardial infarction patients. Furthermore, in patients with a previous myocardial infarction, gated SPET imaging has the potential to detect preserved wall motion in regions with fixed perfusion defects, which might be indicative of residual myocardial viability.

The additive value of gated SPET myocardial perfusion imaging in patients with known and suspected coronary artery disease.

In myocardial perfusion scintigraphy, the clinical significance of fixed defects presents some difficulty. In this study, we evaluated whether additional information on left ventricular function assessed by quantitative gated single-photon emission computed tomography (gated SPET) would increase the diagnostic yield of the study in such patients. We studied 55 patients with a previous myocardial infarction and 20 patients without a previous myocardial infarction using gated SPET 99Tc(m)-tetrofosmin myocardial perfusion imaging. Each patient had to have a persistent perfusion defect consisting of at least three contiguous segments in the same vascular territory. The left ventricle was divided into 20 segments which were analysed for perfusion and wall thickening on a 4-point severity scale. Of the 55 patients with myocardial infarction, 19 (35%) patients showed preserved wall thickening in the region of the previous infarction with fixed perfusion abnormalities, which suggested residual myocardial viability. In the 20 patients without myocardial infarction, preserved wall thickening was seen in 10 (50%) patients with fixed perfusion defects, suggesting an attenuation artefact. Conversely, in 16 (29%) patients in the myocardial infarction group and two (10%) patients in the non-myocardial infarction group normal perfusion was associated with severely diminished wall thickening possibly due to stunning. We found an excellent correlation between wall thickening and left ventricular ejection fraction both for the patients with myocardial infarction and the patients without myocardial infarction (r = 0.86 and r = 0.82, respectively, both P<0.0001). A reasonable correlation between perfusion and left ventricular ejection fraction was found for the patients with myocardial infarction (r = 0.41, P = 0.002), and a non-significant correlation for the patients without myocardial infarction (r = 0.37, P = 0.1). Quantitative gated SPET myocardial imaging allows the detection of residual wall thickening in patients with a previous myocardial infarction who show severe fixed perfusion defects. In patients without myocardial infarction, gated SPET imaging allows differentiation between an attenuation artefact and a fixed perfusion defect due to coronary artery disease. In addition, gated SPET may show diminished ventricular function in normally perfused segments possibly due to myocardial stunning. The addition of gated SPET myocardial perfusion imaging increases diagnostic confidence and may have direct clinical implications for optimal patient management.

Comparison of left ventricular function at rest and post-stress in patients with myocardial infarction: Evaluation with gated SPECT.

BACKGROUND: Quantitative electrocardiogram-gated single photon emission computed tomography (SPECT) myocardial imaging (QGS) is a means of providing functional information about the left ventricle and myocardial perfusion. However, the functional information derived 30 minutes post-stress may be different from the left ventricular (LV) function determined at rest. This study determined whether LV function post-stress would be different from LV function at rest in patients with an earlier myocardial infarction. METHODS AND RESULTS: LV perfusion and ejection fraction (LVEF), were determined by means of both the rest and post-stress acquisition in 58 patients with an earlier myocardial infarction and in 23 patients with a low likelihood of coronary artery disease by using technetium-99m tetrofosmin and the QGS program. The interobserver and intraobserver variability of LVEF was excellent, within a margin of 2%. No significant differences in LVEF were observed between post-stress and rest in the 23 patients with a low likelihood of disease (DeltaLVEF, 0.04% +/- 3.2%, P = not significant). Conversely, the patients with an earlier myocardial infarction showed a significantly lower LVEF post-stress, compared with that at rest (DeltaLVEF, -1.9% +/- 4.2%, P =.002). In 33 patients (57%), the LVEF post-stress was 2% or more lower than the LVEF at rest. Furthermore, reversible ischemia, which was present in 16 patients (28%), did not interact with the DeltaLVEF post-stress, compared with the DeltaLVEF at rest (P = not significant). Parameters such as the stress modality (adenosine stress or exercise), the number of stenosed vessels, or the perfusion defect severity score did not influence the DeltaLVEF post-stress, compared with the DeltaLVEF at rest. CONCLUSIONS: In patients with an earlier myocardial infarction, LV function post-stress may not represent the true resting LV function. Consequently, this result justifies the stratification of patients before starting the gated SPECT study. In patients with an earlier myocardial infarction, the gated acquisition should be performed during the rest study.

Left ventricular function: correlation of quantitative gated SPECT and MR imaging over a wide range of values.

In 21 patients, the authors compared results with quantitative gated single photon emission computed tomography (SPECT) to results with magnetic resonance imaging in the assessment of left ventricular (LV) end-diastolic volume (LVEDV), end-systolic volume (LVESV), and ejection fraction (LVEF). Between the two methods, correlations were good for LVEF (r = 0.85), LVEDV (r = 0.94), and LVESV (r = 0.95). Quantitative gated SPECT can help determine LVEF, LVEDV, and LVESV.

Good correlation between gated single photon emission computed myocardial tomography and contrast ventriculography in the assessment of global and regional left ventricular function.

PURPOSE: The purpose of this study was to determine the reliability of the measured left ventricular ejection fraction (LVEF) and wall motion analysis by the recently introduced quantitative electrocardiographically (ECG)-gated myocardial perfusion single-photon emission computed myocardial tomography technique (gated SPECT) (QGS). MATERIALS AND METHODS: We compared technetium-99 m tetrofosmin gated SPECT imaging and contrast ventriculography in the assessment of global and regional left ventricular function in 74 patients with undiagnosed chest pain of whom 27 sustained a previous myocardial infarction. RESULTS: Linear regression analysis demonstrated that gated SPECT determined LVEF correlated well with LVEF determined from contrast ventriculography (y = 0.95x + 1.9, r2 = 0.84, p < 0.0001). Bland-Altman plot analysis showed no systematic difference between the two sets of values derived from the two imaging approaches over a wide range of LVEF values. Exact agreement of segmental wall motion scores was 460 of 518 (89%) segments with a kappa value of 0.76 (p < 0.0001). CONCLUSION: We conclude that gated SPECT imaging is an accurate and reliable clinical tool to accurately measure global and regional left ventricular function.