Design and Clinical Evaluation of Pharmacologic Stress-Test with Dalargin for SPECT Detection of Viable Myocardium in Patients after Myocardial Infarction

Purpose: To develop a functional stress-test with Dalargin used as a pharmacological stress agent and to study its diagnostic capabilities for quantifying the general and segmental systolic function of the left ventricle in patients with IHD using SPECT and echo methods. Material and methods: The study comprised 29 male patients with CHD-angina of 2-3 functional classes, studied on 15–25 days (on average 20 ± 2.8 days) after a large-focal myocardial infarction. A fractional step-wise injection of Dalargin was performed with step doses as 0.1 mg / kg (1 ml up to a total of 8 ml, with intervals of 90 seconds, for a total of 12 minutes), in a supine position. After each dose of Dalargin, blood pressure, heart rate, ECG were recorded, and an echocardiographic assessment of hemodynamic parameters and local contractility was carried out. At the peak of the effect of dalargin, 99mTc-Tetrofosmin was administered intravenously (370 – 540 MBq), followed by chest SPECT. Results: The optimal dose of dalargin for assessing the contractility of the LV was 0.3 mg/kg. From the data of myocardial perfusion SPECT, at dalargin test, the number of segments with normal regional blood supply increased statistically significantly from 56,0 % to 64,7 %, the number of hypoperfused segments decreased from 41.0% to 33.7% as compared to rest, and the number of non-perfused ones – from 3.0 % to 1.6 %. Spearman’s correlation coefficient between segmental contractility and local perfusion at the top dalargin inotropic effect was high and significant (R=0.67, p<0.01). The sensitivity and specificity of the pharmacological test with intravenous administration of dalargin for prediction of postoperative improvement of perfusion and contractility of the viable myocardium were: sensitivity 78.8 %, specificity 76.4 %, diagnostic accuracy 77.6 %. Conclusion. The use of the agonist of the μ - and δ-opioid receptors dalargin as a pharmacological stress-agent at perfusion SPECT and Stress Echocardiography to assess the contractile reserve of a dysfunctional viable myocardium is informative and appropriate. In patients with IHD who have suffered a myocardial infarction and are referred to myocardial revascularization, dalargin can be employed as an effective stress-agent for assessing the reserve of perfusion and contractility of dysfunctional left ventricular myocardium using perfusion SPECT and echocardiography.

The assessment of left ventricular mechanical dyssynchrony from gated 99mTc-tetrofosmin SPECT and gated 18F-FDG PET by QGS: a comparative study

Background Due to partly conflicting studies, further research is warranted with the QGS software package, with regard to the performance of gated FDG PET phase analysis as compared to gated MPS as well as the establishment of possible cut-off values for FDG PET to define dyssynchrony. Methods Gated MPS and gated FDG PET datasets of 93 patients were analyzed with the QGS software. BW, Phase SD, and Entropy were calculated and compared between the methods. The performance of gated PET to identify dyssynchrony was measured against SPECT as reference standard. ROC analysis was performed to identify the best discriminator of dyssynchrony and to define cut-off values. Results BW and Phase SD differed significantly between the SPECT and PET. There was no significant difference in Entropy with a high linear correlation between methods. There was only moderate agreement between SPECT and PET to identify dyssynchrony. Entropy was the best single PET parameter to predict dyssynchrony with a cut-off point at 62%. Conclusion Gated MPS and gated FDG PET can assess LVMD. The methods cannot be used interchangeably. Establishing reference ranges and cut-off values is difficult due to the lack of an external gold standard. Further prospective research is necessary.

Inhibition of the Hepatic Uptake of 99mTc-Tetrofosmin Using an Organic Cation Transporter Blocker

The accumulation of high levels of 99mTc-tetrofosmin (99mTc-TF) in the hepatobiliary system can lead to imaging artifacts and interference with diagnosis. The present study investigated the transport mechanisms of 99mTc-TF and attempted to apply competitive inhibition using a specific inhibitor to reduce 99mTc-TF hepatic accumulation. In this in vitro study, 99mTc-TF was incubated in HEK293 cells expressing human organic anion transporting polypeptide 1B1 (OATP1B1), OATP1B3, OATP2B1, organic anion transporter 2 (OAT2), organic cation transporter 1 (OCT1), OCT2, and Na+-taurocholate cotransporting polypeptide with or without each specific inhibitor to evaluate the contribution of each transporter to 99mTc-TF transportation. In vivo studies, dynamic planar imaging, and single photon emission computed tomography (SPECT) experiments with rats were performed to observe alterations to 99mTc-TF pharmacokinetics using cimetidine (CMT) as an OCT1 inhibitor. Time–activity curves in the liver and heart were acquired from dynamic data, and the 99mTc-TF uptake ratio was calculated from SPECT. From the in vitro study, 99mTc-TF was found to be transported by OCT1 and OCT2. When CMT-preloaded rats and control rats were compared, the hepatic accumulation of the 99mTc-TF was reduced, and the time to peak heart count shifted to an earlier stage. The hepatic accumulation of 99mTc-TF was markedly suppressed, and the heart-to-liver ratio increased 1.6-fold. The pharmacokinetics of 99mTc-TF were greatly changed by OCT1 inhibitor. Even in humans, the administration of OCT1 inhibitor before cardiac SPECT examination may reduce 99mTc-TF hepatic accumulation and contribute to the suppression of artifacts and the improvement of SPECT image quality.

Cardiotoxicity in breast cancer patients: the role of gated myocardial perfusion SPECT

Funding Acknowledgements Type of funding sources: None. Background Patients undergoing chemotherapy (CHT) for breast cancer (BC) need a monitoring of cardiac function due to the possible onset of cardiotoxicity. Cardiotoxicity may occur with heart failure but is often asymptomatic and is detectable only by assessing an increase in cardiac volumes (left ventricular end-diastolic (LV-EDV) and end-systolic (LV-ESV) volumes) and/or by a reduction of the left ventricular ejection fraction (LV-EF). The primary purpose of this study was to evaluate the role of gated SPECT myocardial perfusion imaging in this setting. Dosimetric evaluation was also assessed. Methods Seventeen BC patients (mean age 55.93 ± 11.04 years)with invasive ductal carcinoma HER2 + treated with surgery and with an anthracycline-based adjuvant CHT, were enrolled. The trend of cardiac function was assessed by evaluation of LV-EF, LV-EDV and LV-ESV using gSPECT in baseline conditions and at 12, 15 and 52 weeks during treatment and then at 6, 12, 24 and 48 months during follow-up. Each patient was studied 15-20 min after injection of 555 MBq of 99mTc-Tetrofosmin with gSPECT (16 frames/cardiac cycle) using an Infinia Hawkeye IV gamma-camera. Dosimetry was assed according to ICRP reports. Results Two out of the 17 patients enrolled left the protocol: one because of a second tumor and the other due to the appearance of cardiotoxicity. 15 patients completed the study: mean LVEF at baseline was 70.67 ± 5.68. The greatest modification occurred after 15th week of treatment, when mean LV-EF showed a significant decrease to 65.67 ± 8.27, while mean LV-EDV and mean LV-ESV increased from 73.60 ± 16.72 up to 84.73 ± 21.11 and from 21.93 ± 7.17 up to 30.27 ± 14.16, respectively. All parameters progressively returned similar to baseline values at the final examination (after 48th month): mean LV-EF 70.20 ± 5.65, LV-EDV 73.40 ± 16.15 and ESV 22.07 ± 7.50. In one case cardiotoxicity occurred at 15th week: LV-EF decreased from 69 to 47%, LV-EDV increased from 92 up to 142 ml and LV-ESV from 28 up to 75 ml. According to our image protocols, effective dose for gSPECT was 3.83 mSv (ICRP 106). The use of gSPET instead of MUGA (6.47 mSv–ICRP 80) allowed a dose effective saving of 2.64 mSv/each control with a total saving of 21.12 mSv/patient. Conclusions Although the small sample size, gSPECT was demonstrated to be an applicable tool for monitoring cardiac function because it correctly identified BC patient with cardiotoxicity. gSPECT also allowed a significant radiation dose saving compared to MUGA: this is particularly relevant in cardiotoxicity studies that require repeated and close evaluations.

Parathyroid Scintigraphy

The visualization of abnormal parathyroid glands is difficult due to their variations in number and localization. Noninvasive parathyroid imaging studies include 99mTc-sestamibi scintigraphy, ultrasonography, computed tomography scanning, magnetic resonance imaging, and positron emission tomography. There is a general consensus that the most sensitive and specific imaging modality, especially when it is combined with single-photon emission CT is the scintigraphy with 99mTc-sestamibi or 99mTc-tetrofosmin. 99mTc-sestamibi scintigraphy significantly increases the role of preoperative scintigraphy in patients with hyperparathyroidism and allows unilateral surgical approach with minimally invasive parathyroidectomy to be used. Generally, three protocols with the use of two radiopharmaceuticals, 99mTc-sestamibi or 99mTc-tetrofosmin, are most widely applied: single-phase dual-isotope subtraction, dual-phase single-isotope and combination of both. Each one of them has specific advantages and disadvantages. While single parathyroid adenomas are localized with greater precision, hyperfunctioning parathyroid hyperplastic cells represent a real challenge to the imaging modalities. Several factors can influence the radionuclide uptake in pathologically changed parathyroid cells, like the size, the level of their functional activity, the quantity of oxyphilic cells, mitochondria, P glycoprotein and other MDR gene products.

A wall based regional innervation/perfusion mismatch assessed by cardiac 123I-mIBG and rest 99mTc-tetrofosmin SPECT to predict arrhythmic events in ischemic heart failure patients

Funding Acknowledgements Type of funding sources: None. Introduction Cardiac 123I-mIBG SPECT imaging provides information on regional myocardial innervation. However, there is no consensus on how to use a, 17-segment based score to assess prognosis. The present study examined whether a simpler regional scoring approach for evaluation of 123I-mIBG SPECT combined with rest 99mTc-tetrofosmin SPECT myocardial perfusion imaging could be used for the prediction of arrhythmic events (AEs) in ischemic heart failure (HF). Methods 261 ischemic HF subjects (NYHA II/III, LVEF ≤35% on gated SPECT) of the ADMIRE-HF study cohort with complete cardiac 123I-mIBG and rest 99mTc-tetrofosmin SPECT studies were enrolled. Both SPECT image sets were read together by 2 experienced nuclear imagers and scored by consensus. In addition to standard 17 segments scoring, the readers classified walls (i.e. anterior, lateral, inferior, septum and apex) as normal, matched defect of innervation and perfusion, mismatched (i.e., innervation defect lager than perfusion defect) or reverse mismatched (i.e., innervation defect smaller than perfusion defect). Cox proportional hazards ratios (HR) were used to determine if the visual segmental wall classification innervation/perfusion mismatch score, 123I-mIBG summed defect scores (SDS), 99mTc-tetrofosmin SDS and innervation/perfusion mismatch SDS, age, LVEF, NYHA class, B-type natriuretic peptide (BNP) and norepinephrine (NE) plasma levels were associated with occurrence of AEs (i.e. sudden cardiac death, sustained VT, resuscitated cardiac arrest, appropriate ICD therapy). Results At 2-year median follow-up, 38 subjects (14.6%) had AEs. Subjects with 1 or 2 mismatched walls were more than twice as likely to have AEs compared with subjects with either 0 or 3-5 mismatched walls (24.0% vs 10.8%, p = 0.006). Cox regression analyses showed that the combination of the presence of visual mismatch in 1-2 walls and BNP and were the only independent predictors of AEs (HR 2.583 [1.261-5.107],p = 0.001) However, compared to the visual mismatch, the contribution of BNP is relatively small (i.e., HR 1.001 [1.000-1.001]). Conclusion In ischemic HF with LVEF ≤35 the highest risk of AEs occurs in subjects with intermediate levels of visual wall-level innervation/perfusion mismatches. Therefore, a simple visual wall-level based assessment of combined cardiac 123I-mIBG and rest 99mTc-tetrofosmin SPECT can be used to differentiate those HF patients at higher AE risk from those with relatively low AE risk. Table 1. Cox regression analysis Variable HR (95% CI) X2 change X2 p-value AE’s 1-2 mismatched segments 2.412 (1.204-4.830) 6.581 5.880 0.010 BNP 1-2 mismatched segments 1.001 (1.000-1.001) 2.538 (1.261-5.107) 13.434 4.129 0.001 Abstract Figure. Kaplan Meier curves for AEs

Cardiac sympathetic denervation in wild-type transthyretin amyloidosis

Background Tissue accumulation of misfolded transthyretin (TTR) may occur because of TTR gene mutations (variant amyloid TTR amyloidosis, ATTRv), or as an age-related phenomenon (wild-type ATTR, ATTRwt). Cardiac sympathetic denervation has been reported in ATTRv, but has never been investigated in ATTRwt. Methods Fifteen consecutive patients with ATTRwt cardiomyopathy (81% men, median age 82 years, no one with prior myocardial infarction) underwent Cadmium Zinc Telluride tomographic imaging for amyloid burden (99mTc-hydroxymethylene diphosphonate - 99mTc-HMDP), innervation (123I-metaiodobenzylguanidine – 123I-MIBG), and perfusion (99mTc-tetrofosmin). Results Median summed 99mTc-HMDP score was 60 (58–62), denoting a severe and diffuse amyloid burden. Planar 123I-MIBG examination showed decreased early and late H/M ratios (late H/M ratio: 1.5 [1.3–1.6], range 1.2–1.9, reference value ≥2.0). Summed 123I-MIBG score was 12 (6–22), with the most prominent denervation in the infero-septal, inferior, and infero-lateral regions; summed rest score was 7 (5–11), with lowest degrees of myocardial perfusion in the inferior and infero-septal regions. The correlation between amyloid burden (as relative 99mTc-HMDP uptake) and innervation (as relative 123I-MIBG uptake) did not achieve statistical significance at both segmental (p=0.252) and regional level (p=0.251). Nevertheless, denervation tended to worsen in parallel with the amyloid burden, and 123I-MIBG scores increased with 99mTc-HMDP scores. Segments and regions with more prominent hypoperfusion were those showing the more intense denervation (r=0.500 and 0.591, respectively; both p&lt;0.001). Conclusions Patients with ATTRwt cardiomyopathy display cardiac sympathetic denervation, particularly in the inferior and septal myocardial wall. Myocardial hypoperfusion has a similar regional pattern, while the amyloid burden is more extensive. Funding Acknowledgement Type of funding source: None