Dataset Information

Detection of anthracycline-induced cardiotoxicity using perfusion-corrected ^99mTc sestamibi SPECT.

ABSTRACT: By the time cardiotoxicity-associated cardiac dysfunction is detectable by echocardiography it is often beyond meaningful intervention. ^99mTc-sestamibi is used clinically to image cardiac perfusion by single photon emission computed tomography (SPECT) imaging, but as a lipophilic cation its distribution is also governed by mitochondrial membrane potential (??_m). Correcting scans for variations in perfusion (using a ??_m-independent perfusion tracer such as (bis(N-ethoxy-N-ethyldithiocarbamato)nitrido ^99mTc(V)) (^99mTc-NOET) could allow ^99mTc-sestamibi to be repurposed to specifically report on ??_m as a readout of evolving cardiotoxicity. Isolated rat hearts were perfused within a ?-detection apparatus to characterize the pharmacokinetics of ^99mTc-sestamibi and ^99mTc-NOET in response to mitochondrial perturbation by hypoxia, ionophore (CCCP) or doxorubicin. All interventions induced ^99mTc-sestamibi washout; hypoxia from 24.9?±?2.6% ID to 0.4?±?6.2%, CCCP from 22.8?±?2.5% ID to -3.5?±?3.1%, and doxorubicin from 23.0?±?2.2% ID to 17.8?±?0.7, p?99mTc-NOET retention (34.0?±?8.0% ID) was unaffected in all cases. Translating to an in vivo rat model, 2 weeks after bolus doxorubicin injection, there was a dose-dependent loss of cardiac ^99mTc-sestamibi retention (from 2.3?±?0.3 to 0.9?±?0.2 ID/g with 10?mg/kg (p?99mTc-NOET retention (0.93?±?0.16 ID/g) was unaffected. ^99mTc-NOET therefore traps in myocardium independently of the mitochondrial perturbations that induce ^99mTc-sestamibi washout, demonstrating proof-of-concept for an imaging approach to detect evolving cardiotoxicity.

SUBMITTER: Safee ZM

PROVIDER: S-EPMC6338786 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Detection of anthracycline-induced cardiotoxicity using perfusion-corrected 99mTc sestamibi SPECT.

Safee Zaitulhusna M ZM Baark Friedrich F Waters Edward C T ECT Veronese Mattia M Pell Victoria R VR Clark James E JE Mota Filipa F Livieratos Lefteris L Eykyn Thomas R TR Blower Philip J PJ Southworth Richard R

Scientific reports 20190118 1

By the time cardiotoxicity-associated cardiac dysfunction is detectable by echocardiography it is often beyond meaningful intervention. 99mTc-sestamibi is used clinically to image cardiac perfusion by single photon emission computed tomography (SPECT) imaging, but as a lipophilic cation its distribution is also governed by mitochondrial membrane potential (ΔΨm). Correcting scans for variations in perfusion (using a ΔΨm-independent perfusion tracer such as (bis(N- ...[more]

PMID: 30659226

Similar Datasets

Project description:BackgroundThe introduction of hybrid SPECT/CT devices enables quantitative imaging in SPECT, providing a methodological setup for quantitation using SPECT tracers comparable to PET/CT. We evaluated a specific quantitative reconstruction algorithm for SPECT data using a 99mTc-filled NEMA phantom. Quantitative and qualitative image parameters were evaluated for different parametrizations of the acquisition and reconstruction protocol to identify an optimized quantitative protocol.ResultsThe reconstructed activity concentration (ACrec) and the signal-to-noise ratio (SNR) of all examined protocols (n = 16) were significantly affected by the parametrization of the weighting factor k used in scatter correction, the total number of iterations and the sphere volume (all, p < 0.0001). The two examined SPECT acquisition protocols (with 60 or 120 projections) had a minor impact on the ACrec and no significant impact on the SNR. In comparison to the known AC, the use of default scatter correction (k = 0.47) or object-specific scatter correction (k = 0.18) resulted in an underestimation of ACrec in the largest sphere volume (26.5 ml) by - 13.9 kBq/ml (- 16.3%) and - 7.1 kBq/ml (- 8.4%), respectively. An increase in total iterations leads to an increase in estimated AC and a decrease in SNR. The mean difference between ACrec and known AC decreased with an increasing number of total iterations (e.g., for 20 iterations (2 iterations/10 subsets) = - 14.6 kBq/ml (- 17.1%), 240 iterations (24i/10s) = - 8.0 kBq/ml (- 9.4%), p < 0.0001). In parallel, the mean SNR decreased significantly from 2i/10s to 24i/10s by 76% (p < 0.0001).ConclusionQuantitative SPECT imaging is feasible with the used reconstruction algorithm and hybrid SPECT/CT, and its consistent implementation in diagnostics may provide perspectives for quantification in routine clinical practice (e.g., assessment of bone metabolism). When combining quantitative analysis and diagnostic imaging, we recommend using two different reconstruction protocols with task-specific optimized setups (quantitative vs. qualitative reconstruction). Furthermore, individual scatter correction significantly improves both quantitative and qualitative results.

Project description:PurposeSentinel lymph node (SLN) biopsy has proven to reliably stage the clinically negative neck in early-stage oral squamous cell carcinoma (OSCC). [99mTc]Tc-tilmanocept may be of benefit in OSCC with complex lymphatic drainage patterns and close spatial relation to SLNs.MethodsA prospective within-patient evaluation study was designed to compare [99mTc]Tc-tilmanocept with [99mTc]Tc-nanocolloid for SLN detection. A total of 20 patients with early-stage OSCC were included, who underwent lymphoscintigraphy with both tracers. Both lymphoscintigraphic images of each patient were evaluated for SLN detection and radiotracer distribution at 2-4 h post-injection.ResultsThe injection site's remaining radioactivity was significantly lower for [99mTc]Tc-tilmanocept (29.9%), compared with [99mTc]Tc-nanocolloid (60.9%; p < 0.001). Radioactive uptake in SLNs was significantly lower for [99mTc]Tc-tilmanocept (1.95%) compared with [99mTc]Tc-nanocolloid (3.16%; p = 0.010). No significant difference was seen in SLN to injection site ratio in radioactivity between [99mTc]Tc-tilmanocept (0.066) and [99mTc]Tc-nanocolloid (0.054; p = 0.232). A median of 3.0 and 2.5 SLNs were identified with [99mTc]Tc-tilmanocept and [99mTc]Tc-nanocolloid, respectively (p = 0.297). Radioactive uptake in higher echelon nodes was not significantly different between [99mTc]Tc-tilmanocept (0.57%) and [99mTc]Tc-nanocolloid (0.86%) (p = 0.052). A median of 2.0 and 2.5 higher echelon nodes was identified with [99mTc]Tc-tilmanocept and [99mTc]Tc-nanocolloid, respectively (p = 0.083).Conclusion[99mTc]Tc-tilmanocept had a higher injection site clearance, but at the same time a lower uptake in the SLN, resulting in an SLN to injection site ratio, which was not significantly different from [99mTc]Tc-nanocolloid. The relatively low-radioactive uptake in SLNs of [99mTc]Tc-tilmanocept may limit intraoperative detection of SLNs, but can be overcome by a higher injection dose.

Project description:BackgroundMolecular breast imaging (MBI) performed with 99mTc sestamibi has been shown to be a valuable technique for the detection of breast cancer. Alternative radiotracers such as 99mTc maraciclatide may offer improved uptake in breast lesions. The purpose of this study was to compare relative performance of 99mTc sestamibi and 99mTc maraciclatide in patients with suspected breast cancer, using a high-resolution dedicated gamma camera for MBI. Women with breast lesions suspicious for malignancy were recruited to undergo two MBI examinations-one with 99mTc sestamibi and one with 99mTc maraciclatide. A radiologist interpreted MBI studies in a randomized, blinded fashion to assign an assessment score (1-5) and measured lesion size. Lesion-to-background (L/B) ratio was measured with region-of-interest analysis.ResultsAmong 39 analyzable patients, 21 malignant tumors were identified in 21 patients. Eighteen of 21 tumors (86%) were seen on 99mTc sestamibi MBI and 19 of 21 (90%) were seen on 99mTc maraciclatide MBI (p = 1). Tumor extent measured with both radiopharmaceuticals correlated strongly with pathologic size (99mTc sestamibi, r = 0.84; 99mTc maraciclatide, r = 0.81). The L/B ratio in detected breast cancers was similar for the two radiopharmaceuticals: 1.55 ± 0.36 (mean ± S.D.) for 99mTc sestamibi and 1.62 ± 0.37 (mean ± S.D.) for 99mTc maraciclatide (p = 0.53). No correlation was found between the L/B ratio and molecular subtype for 99mTc sestamibi (r s = 0.12, p = 0.63) or 99mTc maraciclatide (r s = -0.12, p = 0.64). Of 20 benign lesions, 10 (50%) were seen on 99mTc sestamibi and 9 of 20 (45%) were seen on 99mTc maraciclatide images (p = 0.1). The average L/B ratio for benign lesions was 1.34 ±0.40 (mean ±S.D.) for 99mTc sestamibi and 1.41 ±0.52 (mean ±S.D.) for 99mTc maraciclatide (p = 0.75). Overall diagnostic performance was similar for both radiopharmaceuticals. AUC from ROC analysis was 0.83 for 99mTc sestamibi and 0.87 for 99mTc maraciclatide (p = 0.64).Conclusions99mTc maraciclatide offered comparable lesion uptake to 99mTc sestamibi, in both malignant and benign lesions. There was good correlation between lesion extent and uptake measured from both radiopharmaceuticals. 99mTc maraciclatide offered a marginal (but not significant) improvement in sensitivity over 99mTc sestamibi. Our findings did not support an association between the uptake of either radiopharmaceutical and tumor molecular subtype.Trial registrationClinicalTrials.gov, NCT00888589.

Project description:IntroductionThe incidence of renal tumours is increasing and anatomic imaging cannot reliably distinguish benign tumours from renal cell carcinoma. Up to 30% of renal tumours are benign, with oncocytomas the most common type. Biopsy has not been routinely adopted in many centres due to concerns surrounding non-diagnostic rate, bleeding and tumour seeding. As a result, benign masses are often unnecessarily surgically resected. 99mTc-sestamibi SPECT/CT has shown high diagnostic accuracy for benign renal oncocytomas and other oncocytic renal neoplasms of low malignant potential in single-centre studies. The primary aim of MULTI-MIBI is to assess feasibility of a multicentre study of 99mTc-sestamibi SPECT/CT against a reference standard of histopathology from surgical resection or biopsy. Secondary aims of the study include obtaining estimates of 99mTc-sestamibi SPECT/CT sensitivity and specificity and to inform the design and conduct of a future definitive trial.Methods and analysisA feasibility prospective multicentre study of participants with indeterminate, clinical T1 renal tumours to undergo 99mTc-sestamibi SPECT/CT (index test) compared with histopathology from biopsy or surgical resection (reference test). Interpretation of the index and reference tests will be blinded to the results of the other. Recruitment rate as well as estimates of sensitivity, specificity, positive and negative predictive value will be reported. Semistructured interviews with patients and clinicians will provide qualitative data to inform onward trial design and delivery. Training materials for 99mTc-sestamibi SPECT/CT interpretation will be developed, assessed and optimised. Early health economic modelling using a decision analytic approach for different diagnostic strategies will be performed to understand the potential cost-effectiveness of 99mTc-sestamibi SPECT/CT.Ethics and disseminationEthical approval has been granted (UK HRA REC 20/YH/0279) protocol V.5.0 dated 21/6/2022. Study outputs will be presented and published nationally and internationally.Trial registration numberISRCTN12572202.

Project description:PurposeInvestigate the impact of acquisition time and reconstruction parameters on single-photon emission computed tomography/computed tomography (SPECT/CT) image quality with the ultimate aim of finding the shortest possible acquisition time for clinical whole-body SPECT/CT (WB-SPECT/CT) while maintaining image quality METHODS: The National Electrical Manufacturers Association (NEMA) image quality measurements were performed on a SPECT/CT imaging system using a NEMA International Electrotechnical Commission (IEC) phantom with spherical inserts of varying diameter (10-37 mm), filled with 99m Tc in activity sphere-to-background concentration ratio of 8.5:1. A gated acquisition was acquired and binned data were summed to simulate acquisitions of 15, 8, and 3 s per projection angle. Images were reconstructed on a Hermes (HERMES Medical Solutions AB, Stockholm, Sweden) workstation using eight subsets and between 4 and 24 iterations of the three-dimensional (3D) ordered subset expectation maximization (OSEM) algorithm. Reconstructed images were post-smoothed with 3D Gaussian filter ranging from 0 to 12 mm full-width at half maximum (FWHM). Contrast recovery, background variability, and contrast-to-noise ratio were evaluated RESULTS: As expected, the spheres were more clearly defined as acquisition time and count statistics improved. The optimal iteration number and Gaussian filter were determined from the contrast recovery convergence and level of noise. Convergence of contrast recovery was observed at eight iterations while 12 iterations yielded stabilized values at all acquisition times. In addition, it was observed that applying 3D Gaussian filter of 8-12 mm FWHM suppressed the noise and mitigated Gibbs artifacts. Background variability was larger for small spheres than larger spheres and the noise decreased when acquisition time became longer. A contrast-to-noise ratio >5 was reached for the two smallest spheres of 10 and 13 mm at acquisition times of 8 s CONCLUSION: Optimized reconstruction parameters preserved image quality with reduce acquisition time in present study. This study suggests an optimal protocol for clinical 99m Tc SPECT/CT can be reached at 8 s per projection angle, with data reconstructed using 12 iterations and eight subset of the 3D OSEM algorithm and 8 mm Gaussian post-filter.

Dataset Information

Detection of anthracycline-induced cardiotoxicity using perfusion-corrected ^99mTc sestamibi SPECT.

Publications

Detection of anthracycline-induced cardiotoxicity using perfusion-corrected <sup>99m</sup>Tc sestamibi SPECT.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets