Synthesis, characterization, and radiosynthesis of fluorine-18-AVT-011 as a Pgp chemoresistance imaging marker.

P-glycoprotein (Pgp) is the most studied ATP-binding cassette (ABC) efflux transporter and contributes to chemoresistance. A few tracers have been developed to detect the in-vivo status of chemoresistance using positron emission tomography (PET) imaging. In our study, we have synthesized labeled AVT-011 with fluorine-18 (18F) followed by in-vitro and in-vivo analysis. Tosylate AVT-011 precursor was synthesized and characterized by 1H-NMR and 13C-NMR. AVT-011 was labeled with 18F using the nucleophilic substitution method, and a standard set of quality control was performed. The specificity for Pgp was tested in U87MG cells with and without an inhibitor (tariquidar). The biodistribution and in-vivo stability were tested in the small animals (mice). The biodistribution data of [18F]-AVT-011 was extracted from the PET-CT imaging of breast cancer patients (n = 6). The precursor was synthesized with 36 ± 4% yield and 97 ± 2% purity. The labeling was more than 95% with a 42 ± 2% yield, as evaluated by Radio-HPLC. The cell-binding assay showed a specificity of the tracer for Pgp as the uptake increased by twice after blocking the Pgp receptors. The radiotracer showed a hepatorenal excretion pathway for clearance in an animal study. The uptake was higher in the liver, lungs, spleen, and heart at 15 min and decreased at 60 min. The patients' distribution showed similar uptake patterns as observed in the small animals. [18F]AVT-011 was characterized successfully with high radiochemical purity and yield. The in-vitro and in-vivo studies proved its specificity for Pgp and safe for patient use.

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.

18F-FDG PET Detection of a Medullary Thyroid Carcinoma in a Patient With SMZL.

Incidental thyroid FDG uptake is not rarely encountered on PET studies. In this case, we present an incidental thyroid focus of F-FDG uptake identified in a patient with splenic marginal zone lymphoma during the baseline and the response assessment PET/CT study that proved to be medullary thyroid carcinoma on subsequent histological examination.

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.

Incidence and Significance of Incidental Focal Thyroid Uptake on (18)F-FDG PET Study in a Large Patient Cohort: Retrospective Single-Centre Experience in the United Kingdom.

OBJECTIVE: To assess the prevalence and pathological nature of incidental focal thyroid uptake on (18)F-FDG (2-[(18)F]-fluoro-2-deoxy-D-glucose) PET (positron emission tomography) and examine the role of the maximum standardised uptake value (SUVmax) to differentiate benign from malignant thyroid pathology. MATERIAL AND METHODS: (18)F-FDG PET reports were retrospectively reviewed. Incidental focal tracer uptake in the thyroid was noted in 147 patients (0.5%). Patients with known primary thyroid malignancy were excluded. The final diagnosis was made following ultrasonography of the neck, fine-needle aspiration cytology (FNAC) or histopathology of the surgically resected specimen where surgery was indicated. A Mann-Whitney U test was used to compare the SUVmax of benign and malignant thyroid pathology. Receiver operating characteristic (ROC) analysis was performed to identify an SUVmax cutoff in differentiating benign from malignant pathology. RESULTS: A final diagnosis was achieved in 47/147 (32%) of the patients. The diagnoses included benign lesions in 36 patients and malignancy in 9 patients. In 2 patients, FNAC demonstrated indeterminate follicular lesions; however, surgical excision was not performed. There was a highly significant difference in the mean SUVmax of malignant focal thyroid uptake (15.7 ± 5.9) compared to that of benign lesions (7.1 ± 6.8) with a p value of 0.000123. An SUVmax of 9.1 achieved a sensitivity of 81.6%, specificity of 100% and area under the curve of 0.915 in the ROC analysis differentiating benign from malignant disease. CONCLUSION: The malignancy potential of incidental focal thyroid uptake remains high and warrants prompt and appropriate follow-up by the clinician. The SUVmax may aid in further characterisation of the lesion and its management.

Clinical Utility of SPECT/CT Imaging Post-Radioiodine Therapy: Does It Enhance Patient Management in Thyroid Cancer?

BACKGROUND: The aim of this study was to evaluate post-therapy iodine-131 single-photon emission computed tomography/computed tomography ((131)I-SPECT/CT) imaging in comparison to conventional planar (131)I whole-body imaging, and to assess its clinical impact on the management of patients. METHODS: We retrospectively reviewed planar (131)I whole-body and (131)I-SPECT/CT imaging findings in 67 patients who underwent (131)I therapy for thyroid cancer. Two nuclear medicine physicians reviewed the scans independently. The foci of increased tracer uptake were identified in the neck, thorax and elsewhere. Within the neck, the foci of (131)I-increased uptake were graded qualitatively as probable or definite uptake in thyroid remnants and probable or definite uptake in the lymph nodes. Serum thyroglobulin level, histopathology and other imaging findings served as the reference standard. RESULTS: Of the 67 patients, 57 (85%) had radioiodine avid disease and 10 (15%) demonstrated non-radioiodine avid disease. Overall, post-therapy (131)I-SPECT/CT downstaged lymph node staging in 10 patients and upstaged it in 4 patients. This translated into a change of management for 9/57 (16%) patients with radioiodine avid disease. A change of management was observed in 5/10 patients with non-radioiodine avid disease confirmed in the post-(131)I-SPECT/CT study. Additionally, clinically significant findings such as incidental lung cancer, symptomatic pleural effusion and consolidation were also diagnosed in both groups of patients. CONCLUSION: In patients with thyroid cancer, (131)I-SPECT/CT is a valuable addition to standard post-therapy planar imaging. SPECT/CT also improved diagnostic confidence and provided crucial clinical information leading to change of management for a significant number of these patients.

Metastasis to the thyroid from non-small cell carcinoma of the lung: findings in (18)F-FDG PET/CT study.

The incidence of thyroid metastasis from other primary malignancy is rare. In this case, we present the findings of (18)F-FDG PET/CT in thyroid metastasis from underlying non-small cell carcinoma of the lung and highlight the importance of tracer uptake pattern recognition within the thyroid on (18)F-FDG PET/CT study.

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.

The role of 99mTc-diphosphonate bone SPECT/CT in the ankle and foot.

The evaluation of the osseous ankle and foot pathology often poses a clinical and diagnostic challenge because of the complex anatomy and structural biomechanics of the region. Further investigation involves a multimodality imaging approach. Although both structural and functional imaging techniques have their strengths, namely, the high specificity of the former and superior sensitivity of the latter, they also have a number of limitations when used in isolation. These include the inability to determine the functional significance of pathological anatomical abnormalities or to further characterize or localize abnormal metabolic activity. The development of integrated single-photon emission computed tomography/computed tomography systems has aimed to overcome the limitations of separate anatomical and functional imaging techniques. This may be of particular value in ankle and foot assessments, in which multiple joints may be affected by different pathologies. This review article aims to highlight the role of both structural and functional imaging techniques, with particular emphasis on the incremental value of single-photon emission computed tomography/computed tomography in evaluation of this complex anatomical region.

Thyroid cancer susceptibility polymorphisms: confirmation of loci on chromosomes 9q22 and 14q13, validation of a recessive 8q24 locus and failure to replicate a locus on 5q24.

Five single nucleotide polymorphisms (SNPs) associated with thyroid cancer (TC) risk have been reported: rs2910164 (5q24); rs6983267 (8q24); rs965513 and rs1867277 (9q22); and rs944289 (14q13). Most of these associations have not been replicated in independent populations and the combined effects of the SNPs on risk have not been examined. This study genotyped the five TC SNPs in 781 patients recruited through the TCUKIN study. Genotype data from 6122 controls were obtained from the CORGI and Wellcome Trust Case-Control Consortium studies. Significant associations were detected between TC and rs965513A (p=6.35×10(-34)), rs1867277A (p=5.90×10(-24)), rs944289T (p=6.95×10(-7)), and rs6983267G (p=0.016). rs6983267 was most strongly associated under a recessive model (P(GG vs GT + TT)=0.004), in contrast to the association of this SNP with other cancer types. However, no evidence was found of an association between rs2910164 and disease under any risk model (p>0.7). The rs1867277 association remained significant (p=0.008) after accounting for genotypes at the nearby rs965513 (p=2.3×10(-13)) and these SNPs did not tag a single high risk haplotype. The four validated TC SNPs accounted for a relatively large proportion (∼11%) of the sibling relative risk of TC, principally owing to the large effect size of rs965513 (OR 1.74).

Value of lateral blood pool imaging in patients with suspected stress fractures of the tibia.

AIM: To critically evaluate the use of lateral blood pool imaging in athletes with lower limb pain and with a clinical suspicion of stress fracture. METHODS: Two experienced nuclear medicine physicians evaluated 3-phase bone scans using 99mTc-methylene diphosphonate performed in 50 consecutive patients referred from a specialist sports injury clinic for suspected tibial stress fracture. The vascularity to the tibia as seen on the blood pool (second phase) images in the anterior/posterior views was compared with the lateral/medial view assessments. Stress fractures were presumed to be present when on the delayed images (third phase) there was a focal or fusiform area of increased tracer uptake involving the tibial cortex. Shin splints which are a recognized cause of lower limb pain in athletes mimicking stress fracture were diagnosed if increased tracer uptake was seen extending along the posterior tibial surface with no significant focal or fusiform area of uptake within this. Inter-reviewer agreement for the assessment of vascularity was also assessed using Cohen's Kappa scores. RESULTS: Twenty-four stress fractures in 24 patients and 66 shin splints in 40 patients were diagnosed. In 18 patients stress fracture and shin splints coexisted. In 10 patients no tibial pathology was identified. Of the 24 patients diagnosed with stress fractures, lateral/medial blood pool imaging was superior in the assessment of blood pool activity (P < 0.001) identifying increased vascularity in 21 cases compared with the anterior/posterior views positive in only 11 cases. The inter-reviewer agreement was near perfect for lateral/medial views, κ = 0.86 while very good for anterior/posterior views, κ = 0.68. CONCLUSION: In patients with suspected tibial stress fractures, lateral views of the tibia provide the optimal method for evaluation of vascularity. Prospective studies with quantitative or semi-quantitative assessment of skeletal vascularity could provide supplementary information relating to the pathophysiology of stress fractures, for example, the time scale of vascular changes after a tibial stress fracture, and potentially could have clinical relevance as to the assessment of the severity of stress fractures and their prognosis.

Beware of the focal uptake at the ischium on the bone scan in prostate cancer.

RATIONALE: The isotope bone scan is routinely used in the management of prostate cancer as the skeleton is the second most common area of metastasis after lymph nodes. A classic site of involvement in the pelvis is the ischium, and the aim of this study was to assess the value of single-photon emission computed tomography/computed tomography (SPECT/CT) imaging in patients with focal ischial uptake on the planar scan. MATERIALS AND METHODS: This was a retrospective study of consecutive 150 patients with prostate cancer who were referred for a whole-body bone scan between August 2007 and 2008. Two experienced nuclear medicine consultants along with a musculoskeletal radiologist reviewed the scans. RESULTS: Sixty-eight patients were diagnosed with widespread metastases and 46 patients showed typical degenerative disease changes on planar whole-body imaging. SPECT/CT imaging was done in 36 patients to clarify the diagnosis in areas of indeterminate uptake noted on planar whole-body imaging. Ten of these 36 patients who had focal increased ischial uptake were included in the study. Only three of these 10 patients were diagnosed as having a metastatic lesion with the presence of an enthesopathy, a common finding. CONCLUSION: Isolated focal uptake in the ischium is a relatively common finding in patients with prostate cancer and there is concern that this, on occasion, could be misinterpreted as metastasis. SPECT/CT imaging has an important role in differentiating a benign from a malignant lesion.

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.

SPECT/CT in imaging foot and ankle pathology-the demise of other coregistration techniques.

Disorders of the ankle and foot are common and given the complex anatomy and function of the foot, they present a significant clinical challenge. Imaging plays a crucial role in the management of these patients, with multiple imaging options available to the clinician. The American College of radiology has set the appropriateness criteria for the use of the available investigating modalities in the management of foot and ankle pathologies. These are broadly classified into anatomical and functional imaging modalities. Recently, single-photon emission computed tomography and/or computed tomography scanners, which can elegantly combine functional and anatomical images have been introduced, promising an exciting and important development. This review describes our clinical experience with single-photon emission computed tomography and/or computed tomography and discusses potential applications of these techniques.

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.

Multislice SPECT/CT in benign and malignant bone disease: when the ordinary turns into the extraordinary.

Nuclear medicine has entered a new era of multimodality imaging. Dedicated multislice single-photon emission computed tomography/computed tomography (SPECT/CT) cameras are relatively new additions to the diagnostic armamentarium in nuclear medicine. The integration of SPECT and CT provides precise anatomical localization and may enable characterization of abnormalities identified on planar or SPECT imaging by providing structural information by CT. The evidence in support of SPECT/CT is rapidly amounting but still relatively limited. To date, studies have suggested improved diagnostic confidence and specificity in the diagnosis of bone pathology. The combination of functional information and anatomical localization has the potential to influence medical practice with newer imaging algorithms. This review presents the current evidence and potential indications of SPECT/CT bone imaging in the assessment of benign and malignant conditions.

Cost-effectiveness of 99mTc-sestamibi in predicting response to chemotherapy in patients with lung cancer: systematic review and meta-analysis.

UNLABELLED: Multidrug resistance (MDR) is a major problem in lung cancer. (99m)Tc-methoxyisobutylisonitrile ((99m)Tc-MIBI) has been demonstrated to be a noninvasive marker for the diagnosis of MDR-related P glycoprotein and MDR-associated protein expression in various solid tumors. Studies have shown that (99m)Tc-MIBI could play a significant role in the management of lung cancer; for example, it could be used in the selection of patients for chemotherapy or radiotherapy or in combined protocols before the start of treatment. Accurate selection of chemosensitive patients with (99m)Tc-MIBI would result not only in effective treatment of patients but also in significant cost savings for health care providers. There is increasing pressure on health care providers to consider costs in medical decision making, particularly in the last decade, as several economic evaluations have appeared in the medical literature. The aims of this study were to undertake a systematic review of the performance of (99m)Tc-MIBI imaging in the assessment of treatment resistance in lung cancer and to use the findings of the review in a decision tree analysis of the potential cost-effectiveness of (99m)Tc-MIBI imaging in selecting lung cancer patients for chemotherapy. METHODS: This study included a systematic review of the literature and a meta-analysis together with a cost-effectiveness analysis of studies with a decision tree analysis model. RESULTS: Analysis of the studies revealed that the overall sensitivity of (99m)Tc-MIBI in identifying responders to chemotherapy was 94%, the specificity was 90%, and the accuracy was 92%. The sensitivity analysis revealed an incremental cost-effectiveness ratio of greater than pound30,000 ( approximately $42,900) for the strategy of treating all patients to recover the small loss of life expectancy (7.5 d) associated with the use of (99m)Tc-MIBI to preselect patients for chemotherapy. CONCLUSION: (99m)Tc-MIBI SPECT can accurately predict which patients with lung cancer will respond to chemotherapy. The use of (99m)Tc-MIBI to preselect patients for chemotherapy has the potential to yield significant cost savings in the health care system without a significant loss of life expectancy for patients.

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.