Receptor-Targeted Peptide Conjugates Based on Diphosphines Enable Preparation of 99mTc and 188Re Theranostic Agents for Prostate Cancer.

Benchtop 99Mo/99mTc and 188W/188Re generators enable economical production of molecular theranostic 99mTc and 188Re radiopharmaceuticals, provided that simple, kit-based chemistry exists to radiolabel targeting vectors with these radionuclides. We have previously described a diphosphine platform that efficiently incorporates 99mTc into receptor-targeted peptides. Here, we report its application to label a prostate-specific membrane antigen (PSMA)-targeted peptide with 99mTc and 188Re for diagnostic imaging and systemic radiotherapy of prostate cancer. Methods: Two diphosphine-dipeptide bioconjugates, DP1-PSMAt and DP2-PSMAt, were formulated into kits for radiolabeling with 99mTc and 188Re. The resulting radiotracers were studied in vitro, in prostate cancer cells, and in vivo in mouse xenograft models, to assess similarity of uptake and biodistribution for each 99mTc/188Re pair of agents. Results: Both DP1-PSMAt and DP2-PSMAt could be efficiently radiolabeled with 99mTc and 188Re using kit-based methods to furnish the isostructural compounds M-DP1-PSMAt and M-DP2-PSMAt (M = [99mTc]Tc, [188Re]Re). All 99mTc/188Re radiotracers demonstrated specific uptake in PSMA-expressing prostate cancer cells, with negligible uptake in prostate cancer cells that did not express PSMA or in which PSMA uptake was blocked. M-DP1-PSMAt and M-DP2-PSMAt also exhibited high tumor uptake (18-30 percentage injected dose per gram at 2 h after injection), low retention in nontarget organs, fast blood clearance, and excretion predominantly via a renal pathway. Importantly, each pair of 99mTc/188Re radiotracers showed near-identical biologic behavior in these experiments. Conclusion: We have prepared and developed novel pairs of isostructural PSMA-targeting 99mTc/188Re theranostic agents. These generator-based theranostic agents have potential to provide access to the benefits of PSMA-targeted diagnostic imaging and systemic radiotherapy in health care settings that do not routinely have access to either reactor-produced 177Lu radiopharmaceuticals or PET/CT infrastructure.

Protocols for Dual Tracer PET/SPECT Preclinical Imaging.

BACKGROUND: Multi-tracer PET/SPECT imaging enables different modality tracers to be present simultaneously, allowing multiple physiological processes to be imaged in the same subject, within a short time-frame. Fluorine-18 and technetium-99m, two commonly used PET and SPECT radionuclides, respectively, possess different emission profiles, offering the potential for imaging one in the presence of the other. However, the impact of the presence of each radionuclide on scanning the other could be significant and lead to confounding results. Here we use combinations of 18F and 99mTc to explore the challenges posed by dual tracer PET/SPECT imaging, and investigate potential practical ways to overcome them. METHODS: Mixed-radionuclide 18F/99mTc phantom PET and SPECT imaging experiments were carried out to determine the crossover effects of each radionuclide on the scans using Mediso nanoScan PET/CT and SPECT/CT small animal scanners. RESULTS: PET scan image quality and quantification were adversely affected by 99mTc activities higher than 100 MBq due to a high singles rate increasing dead-time of the detectors. Below 100 MBq 99mTc, PET scanner quantification accuracy was preserved. SPECT scan image quality and quantification were adversely affected by the presence of 18F due to Compton scattering of 511 keV photons leading to over-estimation of 99mTc activity and increased noise. However, 99mTc:18F activity ratios of > 70:1 were found to mitigate this effect completely on the SPECT. A method for correcting for Compton scatter was also explored. CONCLUSION: Suitable combinations of injection sequence and imaging sequence can be devised to meet specific experimental multi-tracer imaging needs, with only minor or insignificant effects of each radionuclide on the scan of the other.

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

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-ethoxy-N-ethyldithiocarbamato)nitrido 99mTc(V)) (99mTc-NOET) could allow 99mTc-sestamibi to be repurposed to specifically report on ΔΨm as a readout of evolving cardiotoxicity. Isolated rat hearts were perfused within a γ-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 < 0.05. Cardiac 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 < 0.05)), while 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.

Lung clearance of inhaled aerosol of Tc-99m-methoxyisobutyl isonitrile: relationships with cigarette smoking, age and gender.

Tc-99m-methoxyisobutyl isonitrile (Tc-99m-MIBI) is a radiolabelled xenobiotic, the disappearance rate of which from lungs following inhalation as a radioaerosol correlates inversely with bronchopulmonary multidrug resistance protein 1 (MRP1) expression. Tc-99m-MIBI clearance has previously been shown to be delayed in cigarette smokers. The aim of the current study was to determine whether smoking correlates with bronchopulmonary MRP1 expression, to confirm that Tc-99m-MIBI disappearance rate from the lungs following inhalation is delayed in smokers, and to determine the effects of gender and age on disappearance rate. Participants underwent dynamic imaging for 40 min over the lungs following inhalation of Tc-99m-MIBI using a double-headed gamma camera. The half-time of clearance was obtained from geometric mean of anterior and posterior counts and averaged between the two lungs. Paraffin-embedded tissue obtained from healthy lung during surgery in 13 patients was graded immunohistochemically for MRP1 as negative (0), weak (1), moderate (2) or strong (3). In 4 non-smokers, grading was 1 in three and 0 in one. In 9 smokers, in contrast, expression was graded 2-3 in 8 and 1 in one (P<0·02). Mean clearance half-time in smokers (142 ± 29 min; n = 17) was longer than in non-smokers (91 ± 14 min; n = 18; P<0·0001). In non-smokers, half-times were not significantly different between men (96 ± 16; n = 6) min and women (88 ± 12 min; P = 0·2). Combining genders into one group, half-time correlated with participant age (P = 0·0005). We conclude that smoking upregulates MRP1 and delays clearance of inhaled Tc-99m-MIBI. There is no significant gender difference in non-smokers but ageing is associated with longer clearance half-times.

Characterization of attenuation and respiratory motion artifacts and their influence on SPECT MP image evaluation using a dynamic phantom assembly with variable cardiac defects.

BACKGROUND: A phantom assembly that simulates the respiratory motion of the heart was used to investigate artifacts and their impact on defect detection. METHODS: SPECT/CT images were acquired for phantoms with and without small and large cardiac defects during normal and deep breathing, and also at four static respiratory phases. Acquisitions were reconstructed with and without AC, and with misalignment of transmission and emission scans. A quantitative analysis was performed to assess artifacts. Two physicians reported on defect presence or absence and their results were evaluated. RESULTS: All large defects were correctly reported. Attenuation reduced uptake in the basal LV walls, increasing FN physicians' reports for small defects. Respiratory motion reduced uptake mainly in the anterior and inferior walls increasing FP and FN reports on images without and with small defects, respectively. Artifacts due to misalignment between CT and SPECT scans in normal breathing phantoms did not influence the physicians' reports. CONCLUSIONS: Attenuation and respiratory motion correction should be applied to reduce artifacts before reporting on small defects in deep breathing conditions. Artifacts due to misalignment between CT and SPECT scans do not affect defect detection in normal breathing when the LV is co-registered in SPECT and CT images prior to AC.

Impact of respiratory motion correction on SPECT myocardial perfusion imaging using a mechanically moving phantom assembly with variable cardiac defects.

BACKGROUND: The aim of this study was to determine the impact of respiratory motion correction on SPECT MPI and on defect detection using a phantom assembly. METHODS: SPECT/CT data were acquired using an anthropomorphic phantom with inflatable lungs and with an ECG beating and moving cardiac compartment. The heart motion followed the respiratory pattern in the cranio-caudal direction to simulate normal or deep breathing. Small or large transmural defects were inserted into the myocardial wall of the left ventricle. SPECT/CT images were acquired for each of the four respiratory phases, from exhale to inhale. A respiratory motion correction was applied using an image-based method with transformation parameters derived from the SPECT data by a non-rigid registration algorithm. A report on defect detection from two physicians and a quantitative analysis on MPI data were performed before and after applying motion correction. RESULTS: Respiratory motion correction eliminated artifacts present in the images, resulting in a uniform uptake and reduction of motion blurring, especially in the inferior and anterior regions of the LV myocardial walls. The physicians' report after motion correction showed that images were corrected for motion. CONCLUSIONS: A combination of motion correction with attenuation correction reduces artifacts in SPECT MPI. AC-SPECT images with and without motion correction should be simultaneously inspected to report on small defects.

Exploiting the Metal-Chelating Properties of the Drug Cargo for In Vivo Positron Emission Tomography Imaging of Liposomal Nanomedicines.

The clinical value of current and future nanomedicines can be improved by introducing patient selection strategies based on noninvasive sensitive whole-body imaging techniques such as positron emission tomography (PET). Thus, a broad method to radiolabel and track preformed nanomedicines such as liposomal drugs with PET radionuclides will have a wide impact in nanomedicine. Here, we introduce a simple and efficient PET radiolabeling method that exploits the metal-chelating properties of certain drugs (e.g., bisphosphonates such as alendronate and anthracyclines such as doxorubicin) and widely used ionophores to achieve excellent radiolabeling yields, purities, and stabilities with 89Zr, 52Mn, and 64Cu, and without the requirement of modification of the nanomedicine components. In a model of metastatic breast cancer, we demonstrate that this technique allows quantification of the biodistribution of a radiolabeled stealth liposomal nanomedicine containing alendronate that shows high uptake in primary tumors and metastatic organs. The versatility, efficiency, simplicity, and GMP compatibility of this method may enable submicrodosing imaging studies of liposomal nanomedicines containing chelating drugs in humans and may have clinical impact by facilitating the introduction of image-guided therapeutic strategies in current and future nanomedicine clinical studies.

Does the Clearance of Inhaled (99m)Tc-Sestamibi Correlate with Multidrug Resistance Protein 1 Expression in the Human Lung?

Purpose To examine the relation between the lung elimination rate of inhaled technetium 99m ((99m)Tc)-sestamibi and immunohistochemical expression of bronchopulmonary multidrug resistance protein 1 (MRP1) and permeability glycoprotein (P-gp) and assess the repeatability of the inhaled (99m)Tc-sestamibi clearance technique. Materials and Methods (99m)Tc-sestamibi is a known substrate for P-gp and MRP1, which are established cellular drug efflux transporters. The elimination rate of (99m)Tc-sestamibi from the lungs after inhalation as an aerosol has been hypothesized to be regulated by expression of these transporters. Institutional ethics committee approval was received for this prospective study. Written informed consent was obtained from all participants. The clearance of inhaled (99m)Tc-sestamibi from the lungs of 13 patients due to undergo surgery for primary lung cancer (five of 13) or spontaneous pneumothorax (eight of 13) was estimated after dynamic imaging of the lungs during a period of 40 minutes. The time taken to clear 50% of inhaled sestamibi (T1/2) was compared with a semiquantitative immunohistochemical assessment (grade 0-3) of MRP1 and P-gp expression in the lung by using parametric and nonparametric tests. The study was repeated in five participants to assess the repeatability of the technique by using a Bland Altman analysis method. Results MRP1 expression was seen in 12 of 13 patients, while P-gp expression was seen in only two. The mean (99m)Tc-sestamibi elimination rate was faster in patients (n = 6) with low levels of MRP1 expression (grade 0-1) and mean T1/2 of 105 minutes ± 20 (standard deviation), compared with those with higher levels of MRP1 expression (grade 2-3, n = 7) and mean T1/2 of 149 minutes ± 28 (P = .008). Bland-Altman analysis revealed excellent agreement between test and retest values. Conclusion Inhaled (99m)Tc-sestamibi clearance study is a repeatable technique demonstrating significant correlation with MRP1 expression in the lungs. (©) RSNA, 2016.

Technical Pitfalls and Limitations of SPECT/CT.

The synergy of functional and anatomic information in hybrid systems has undoubtedly enhanced the diagnostic potential of radionuclide imaging in recent years, contributing to the advancement of SPECT/CT in clinical practice. Since the introduction of commercial SPECT/CT in the late 1990 s, the field has seen rapid expansion and development toward multidetector CT subsystems, establishing the role of SPECT/CT as a routine imaging tool. It is, however, important to discuss possible challenges and technical limitations of such systems and how these influence imaging outcomes. In particular, the issues of patient motion and spatial misalignment of the SPECT and CT modalities, data corrections such as those for photon attenuation, and the choice of CT acquisition protocols in relation to radiation exposure are discussed in the article.

An audit of half-count myocardial perfusion imaging using resolution recovery software.

INTRODUCTION: The Nuclear Medicine Software Quality Group of the Institute of Physics and Engineering in Medicine has conducted a multicentre, multivendor audit to evaluate the use of resolution recovery software from several manufacturers when applied to myocardial perfusion data with half the normal counts acquired under a variety of clinical protocols in a range of departments. The objective was to determine whether centres could obtain clinical results with half-count data processed with resolution recovery software that were equivalent to those obtained using their normal protocols. MATERIALS AND METHODS: Sixteen centres selected 50 routine myocardial perfusion studies each, from which the Nuclear Medicine Software Quality Group generated simulated half-count studies using Poisson resampling. These half-count studies were reconstructed using resolution recovery and the clinical reports compared with the original reports from the full-count data. A total of 769 patient studies were processed and compared. RESULTS: Eight centres found only a small number of clinically relevant discrepancies between the two reports, whereas eight had an unacceptably high number of discrepancies. There were no significant differences in acquisition parameters between the two groups, although centres finding a high number of discrepancies were more likely to perform both rest and stress scans on normal studies. CONCLUSION: Half of the participating centres could potentially make use of resolution recovery to reduce the administered activity for myocardial perfusion scans without changing their routine acquisition protocols. The other half could consider adjusting the reconstruction parameters used with their resolution recovery software if they wish to use reduced activity successfully.

Real-time differential tracking of human neutrophil and eosinophil migration in vivo.

BACKGROUND: Hitherto, in vivo studies of human granulocyte migration have been based on indiscriminate labeling of total granulocyte populations. We hypothesized that the kinetics of isolated human neutrophil and eosinophil migration through major organs in vivo are fundamentally different, with the corollary that studying unseparated populations distorts measurement of both. METHODS: Blood neutrophils and eosinophils were isolated on 2 separate occasions from human volunteers by using Current Good Manufacturing Practice CD16 CliniMACS isolation, labeled with technetium 99m-hexamethylpropyleneamine oxime, and then reinfused intravenously. The kinetics of cellular efflux were imaged over 4 hours. RESULTS: Neutrophils and eosinophils were isolated to a mean purity of greater than 97% and greater than 95%, respectively. Activation of neutrophils measured as an increase in their CD11b mean fluorescence intensity in whole blood and after isolation and radiolabeling was 25.98 ± 7.59 and 51.82 ± 17.44, respectively, and was not significant (P = .052), but the mean fluorescence intensity of CD69 increased significantly on eosinophils. Analysis of the scintigraphic profile of lung efflux revealed exponential clearance of eosinophils, with a mean half-life of 4.16 ± 0.11 minutes. Neutrophil efflux was at a significantly slower half-life of 13.72 ± 4.14 minutes (P = .009). The migration of neutrophils and eosinophils was significantly different in the spleen at all time points (P = .014), in the liver at 15 minutes (P = .001), and in the bone marrow at 4 hours (P = .003). CONCLUSIONS: The kinetics of migration of neutrophils and eosinophils through the lung, spleen, and bone marrow of human volunteers are significantly different. Study of mixed populations might be misleading.

Imaging Inflammation in Asthma: Real Time, Differential Tracking of Human Neutrophil and Eosinophil Migration in Allergen Challenged, Atopic Asthmatics in Vivo.

BACKGROUND: It is important to study differential inflammatory cellular migration, particularly of eosinophils and neutrophils, in asthma and how this is influenced by environmental stimuli such as allergen exposure and the effects of anti asthma therapy. METHODS: We isolated blood neutrophils and eosinophils from 12 atopic asthmatic human volunteers (Group 1 - four Early Allergic Responders unchallenged (EAR); Group 2 - four Early and Late Allergic Responders (LAR) challenged; Group 3 - four EAR and LAR challenged and treated with systemic corticosteroids) using cGMP CD16 CliniMACS. Cells were isolated prior to allergen challenge where applicable, labelled with (99m)Tc-HMPAO and then re-infused intravenously. The kinetics of cellular influx/efflux into the lungs and other organs were imaged via scintigraphy over 4 h, starting at 5 to 6 h following allergen challenge where applicable. RESULTS: Neutrophils and eosinophils were isolated to a mean (SD) purity of 98.36% (1.09) and 96.31% (3.0), respectively. Asthmatic neutrophils were activated at baseline, mean (SD) CD11b(High) cells 46 (10.50) %. Isolation and radiolabelling significantly increased their activation to > 98%. Eosinophils were not activated at baseline, CD69(+) cells 1.9 (0.6) %, increasing to 38 (3.46) % following isolation and labelling. Analysis of the kinetics of net eosinophil and neutrophil lung influx/efflux conformed to a net exponential clearance with respective mean half times of clearance 6.98 (2.18) and 14.01 (2.63) minutes for Group 1, 6.03 (0.72) and 16.04 (2.0) minutes for Group 2 and 5.63 (1.20) and 14.56 (3.36) minutes for Group 3. These did not significantly differ between the three asthma groups (p > 0.05). CONCLUSIONS: Isolation and radiolabelling significantly increased activation of eosinophils (CD69) and completely activated neutrophils (CD11b(High)) in all asthma groups. Net lung neutrophil efflux was significantly slower than that of eosinophils in all asthma study groups. There was a trend for pre-treatment with systemic corticosteroids to reduce lung retention of eosinophils following allergen challenge.

Integration of advanced 3D SPECT modeling into the open-source STIR framework.

PURPOSE: The Software for Tomographic Image Reconstruction (STIR, http://stir.sourceforge.net) package is an open source object-oriented library implemented in C++. Although its modular design is suitable for reconstructing data from several modalities, it currently only supports Positron Emission Tomography (PET) data. In this work, the authors present results for Single Photon Emission Computed Tomography (SPECT) imaging. METHODS: This was achieved by the complete integration of a 3D SPECT system matrix modeling library into STIR. RESULTS: The authors demonstrate the flexibility of the combined software by reconstructing simulated and acquired projections from three different scanners with different iterative algorithms of STIR. CONCLUSIONS: The extension of the open source STIR project with advanced SPECT modeling will enable the research community to study the performance of several algorithms on SPECT data, and potentially implement new algorithms by expanding the existing framework.

UK audit of quantification of left-ventricular function using gated myocardial perfusion imaging.

PURPOSE: The aim of the study was to evaluate UK-wide interinstitutional reproducibility of left-ventricular functional parameters, end-systolic volume, end-diastolic volume and ejection fraction, obtained from gated myocardial perfusion imaging (GMPI) studies using technetium-99m-labelled radiopharmaceuticals. The study was carried out by the UK Institute of Physics and Engineering in Medicine Nuclear Medicine Software Quality Group. MATERIALS AND METHODS: Ten anonymized clinical GMPI studies, five with normal perfusion and five with perfusion defects, were made available in DICOM and proprietary formats for download and through manufacturers' representatives. Two of the studies were duplicated in order to assess intraoperator repeatability, giving a total of 12 studies. Studies were made available in 8 and 16 frames/cycle. RESULTS: A total of 58 institutions across England, Scotland, Wales and Northern Ireland participated in this study using six different computer packages. Studies were processed at centres using their normal clinical computers and software. The overall mean±SD ejection fraction for all centres was 58.5±3%; the mean end-diastolic volume was 114±12 ml and the mean end-systolic volume was 54±6 ml. The results were affected by the number of frames per cycle and by the postprocessing computer package, but not by the reconstruction filter in the filtered back-projection. CONCLUSION: Calculation of functional parameters from GMPI using technetium-99m-labelled radiopharmaceuticals is reliable and shows limited variability across the UK.

An audit of manufacturers' implementation of reconstruction filters in single-photon emission computed tomography.

AIM: The Nuclear Medicine Software Quality Group of the Institute of Physics and Engineering in Medicine has conducted an audit to compare the ways in which different manufacturers implement the filters used in single-photon emission computed tomography. The aim of the audit was to identify differences between manufacturers' implementations of the same filter and to find means for converting parameters between systems. METHODS: Computer-generated data representing projection images of an ideal test object were processed using seven different commercial nuclear medicine systems. Images were reconstructed using filtered back projection and a Butter worth filter with three different cutoff frequencies and three different orders. RESULTS: The audit found large variations between the frequency-response curves of what were ostensibly the same filters on different systems. The differences were greater than could be explained simply by different Butter worth formulae. Measured cutoff frequencies varied between 40 and 180% of that expected. There was also occasional confusion with respect to frequency units. CONCLUSION: The audit concluded that the practical implementation of filtering, such as the size of the kernel, has a profound effect on the results, producing large differences between systems. Nevertheless, this work shows how users can quantify the frequency response of their own systems so that it will be possible to compare two systems in order to find filter parameters on each that produce equivalent results. These findings will also make it easier for users to replicate filters similar to other published results, even if they are using a different computer system.

Assessment of Inter-modality Spatial Alignment Accuracy in Hybrid Single Photon Emission Computed Tomography in Patients with Hand and Wrist Pain.

Single photon emission computed tomography (SPECT) and computed tomography (CT) integrated in one system (SPECT/CT) is an effective co-registration technique that helps to localize and characterize lesions in the hand and wrist. However, patient motion may cause misalignment between the two modalities leading to potential misdiagnosis. The aim of the present study was to evaluate the hardware-based registration accuracy of multislice SPECT/CT of the hand and wrist and to determine the effect of misalignment errors on diagnostic accuracy. A total of 55 patients who had multislice SPECT/CT of the hand and wrist between July 2008 and January 2010 were included. Two reviewers independently evaluated the fused images for any misalignments with six degrees of freedom: Translation and rotation in the X, Y and Z directions. The results were tested against an automated fusion tool (Syntegra). More than half of the patients had moved during SPECT scanning (Reviewer 1: 29 patients; Reviewer 2: 30 patients) and they all originated in the Y-direction translation (vertical hand motion). Five fused images had significant misalignment errors that could have led to misdiagnosis. The Wilcoxon test indicated statistically non-significant difference (P > 0.05) between reviewers and statistically non-significant difference between the reviewers and software registration. The study also showed high inter-reviewer agreement (κ = 0.87). Hand movement during the SPECT scan was common, but significant misalignments and subsequent misdiagnosis were infrequent. Future studies should investigate the use of hand and wrist immobilization devices and reductions of scan time to minimize patient motion.

Comparison of 10 versus 20 min SPECT 99mTc-MDP bone scans: use of 3D-OSEM image reconstruction with distance-dependent resolution modelling.

BACKGROUND: Iterative reconstruction with system response modelling has been implemented in commercial software by manufacturers for distance-dependent resolution modelling (DRM) of the collimator physical effects. Initial experience with such algorithms also shows improvements in noise characteristics with lower dependency on counting statistics. In this study the performance of one such algorithm, the Philips Astonish, was assessed for bone single-photon emission computed tomography (SPECT) acquired at count levels reduced by half on technetium-99m methylene diphosphonate scans. METHODS: For every SPECT scan, two sets of images were generated with the aid of concurrent data acquisition: (i) a conventional scan used routinely for reporting at 20 s per projection reconstructed with filtered back-projection (FBP20 s) and (ii) a scan at 10 s per projection reconstructed with Astonish (DRM10 s). Phantom and pilot patient data were used to initially establish optimal reconstruction parameters. Subsequently, patient studies (n=28) were scored independently by two experienced observers (blinded to reconstruction method or acquisition time) for image quality based on a scale of 1-5. Observers were also asked to report the number of observed lesions in each scan. RESULTS: Results show that scores were better or equivalent for the vast majority of DRM10 s images compared with FBP20 s with statistically significant differences between the two methods (observer A: mean DRM10 s=4.3±0.5, mean FBP20 s=3.8±0.8, P=0.0064; observer B: mean DRM10 s=3.6±0.8, mean FBP20 s=3.1±0.9, P=0.0073). Improvements in image quality for DRM10 s were reported on 16 out of 28 scans for observer A and 15 out of 28 scans for observer B, whereas 8 out of 28 and 9 out of 28 scans received equivalent scores, respectively. The total number of lesions reported for both DRM10 s and FBP20 s was 72 for both observers showing no differences between the two methods. CONCLUSION: These results indicate that the use of the DRM algorithm has the potential for reducing bone SPECT acquisition times by half without compromising current levels of image quality and diagnostic value, or reduce the injected dose when radioactivity supply is limited.

The added value of multislice SPECT/CT in patients with equivocal bony metastasis from carcinoma of the prostate.

PURPOSE: The purpose of this study was to investigate the additional value of single photon emission computed tomography/computed tomography (SPECT/CT) over whole-body planar bone scintigraphy and SPECT in prostate cancer patients in terms of diagnostic confidence, inter-reviewer agreement and the possible impact on the clinical management. METHODS: This was a retrospective review of 40 consecutive prostate cancer patients (mean age 71 years) who underwent (99m)Tc-methylene diphosphonate (MDP) whole-body planar bone scintigraphy, SPECT and SPECT/CT between April 2006 and April 2008. The images were evaluated by two independent reviewers; inter-reviewer agreement was evaluated using a weighted kappa score. Each focus of abnormal increased tracer uptake was recorded using a 4-point diagnostic confidence scale. Institutional Review Board approval was obtained. RESULTS: Fifty lesions on planar bone scintigraphy in the 40 patients were evaluated. On reporting the planar study and SPECT scans, reviewers rated 61% of lesions as equivocal. On reporting the SPECT/CT scans only 8% of lesions were rated as equivocal, 24% were rated as malignant and 68% as benign. Weighted kappa scores for inter-reviewer agreement were 0.43 for bone scintigraphy, 0.56 for SPECT and 0.87 for SPECT/CT. All were significant at p < 0.0001. Follow-up imaging confirmed the SPECT/CT diagnoses in 14 patients. CONCLUSION: The addition of SPECT/CT resulted in a significant reduction of equivocal reports; a definitive diagnosis was given in the majority of the patients due to the improved diagnostic confidence compared to planar or SPECT imaging alone in prostate cancer patients with suspected bone metastases.

Synergistic impact of attenuation correction and gating in routine myocardial SPECT reporting: 2 year follow-up study.

AIM: To look at the combined impact of non-uniform attenuation correction (AC) and gated SPECT in the visual interpretation of myocardial SPECT imaging. This was compared to the individual benefit obtained by adding AC information and gated SPECT information to non-AC image information. MATERIALS: We retrospectively studied a group of 141 patients with a 22-26 month follow-up who underwent myocardial perfusion scintigraphy imaging. All the studies were corrected for attenuation with Gd line source transmission data and were ECG gated. In patients who had abnormal studies, follow-up coronary angiography information was also obtained in addition to medical follow-up information. METHODS: Two experienced nuclear medicine physicians interpreted the images independently and were blinded to the other person's report. Non-attenuation corrected data was first evaluated followed by attenuation corrected data and gated SPECT data. Four approaches to interpretation of images were undertaken: (1) non-AC images only, (2) non-AC+AC images, (3) non-AC+gated images, and (4) non-AC+AC+gated images. Study results were divided into four categories based on how confident the observers were of the diagnosis: (1) normal, (2) borderline normal, (3) borderline abnormal, and (4) abnormal. RESULTS: When results for sensitivity and specificity using the four different interpretation techniques were compared there was a statistically significant improvement in the specificity compared to non-AC image (48%) with the addition of AC (77%) and gating (82%) information (P<0.001). The best improvement in the specificity was noted when both AC and gated information (91%) was used along with non-AC information. The normalcy rates almost doubled following the addition of AC and gated data. There was also a decrease in the number of borderline results, showing an improvement in the reporter confidence in interpreting myocardial SPECT studies. Sensitivity, however, did not show a significant change between the four different approaches to interpretation of the study. CONCLUSION: Attenuation correction and gating when combined have a synergistic impact upon improving the specificity of myocardial SPECT reporting when compared to the use of individual techniques alone to improve the specificity.