Utility of 68 Ga-DOTA-Exendin-4 positron emission tomography-computed tomography imaging in distinguishing between insulinoma and nesidioblastosis in patients with confirmed endogenous hyperinsulinaemic hypoglycaemia.

BACKGROUND: Because management is very different, it is important to differentiate between small focal insulinomas and diffuse pancreatic dysplasia (nesidioblastosis) in patients with confirmed endogenous hyperinsulinaemic hypoglycaemia (EHH). Most insulinomas highly express glucagon-like peptide-1 receptors enabling positron emission tomography-computed tomography imaging with its radiolabelled analogue; 68 Ga-DOTA-Exendin-4 (Exendin). AIM: To determine: (i) the utility of Exendin in EHH patients in a clinical setting; and (ii) whether the degree of Exendin uptake differentiates non-insulinoma pancreatogenous hypoglycaemia syndrome (NIPHS) from post-gastric bypass hypoglycaemia (PGBH). METHODS: This retrospective study reviewed the clinical, biochemistry and prior imaging findings in confirmed EHH patients referred for Exendin. Accuracy of Exendin was based on surgical findings and treatment outcomes. Finally, average Exendin uptake (SUVmax) of five PGBH studies was compared with the SUVmax of a key NIPHS case report. RESULTS: Twenty of 25 consecutive patients had confirmed EHH. Exendin located insulinomas in eight of nine patients enabling successful surgical excision with rapid and durable cure. Exendin correctly identified diffuse nesidioblastosis in two of three cases requiring partial pancreatectomy for hypoglycaemia control. All three relapsed within 1.7 years with one needing completion pancreatectomy. Establishing the cause in the remainder relied on other investigations, clinical correlation and response to empirical treatment. Finally, Exendin SUVmax could not distinguish between NIPHS and PGBH. CONCLUSION: In EHH patients, Exendin accurately identifies the site of insulinoma and thereby differentiates it from nesidioblastosis but negative findings should not be ignored. Exendin is unlikely to differentiate between normal pancreatic uptake, NIPHS and PGBH.

Head-to-head comparison of cerebral blood flow single-photon emission computed tomography and 18 F-fluoro-2-deoxyglucose positron emission tomography in the diagnosis of Alzheimer disease.

BACKGROUND: Clinical diagnosis of Alzheimer disease (AD) is only 70% accurate. Reduced cerebral blood flow (CBF) and metabolism in parieto-temporal and posterior cingulate cortex may assist diagnosis. While widely accepted that 18 F-fluoro-2-deoxyglucose positron emission tomography (18 F-FDG PET) has superior accuracy to CBF-SPECT for AD, there are very limited head-to-head data from clinically relevant populations and these studies relied on clinical diagnosis as the reference standard. AIMS: To compare directly the accuracy of CBF-SPECT and 18 F-FDG PET in patients referred for diagnostic studies in detecting ß-amyloid PET confirmed AD. METHODS: A total of 126 patients, 56% with mild cognitive impairment and 44% with dementia, completed both CBF-SPECT and 18 F-FDG PET as part of their diagnostic assessment, and subsequently underwent ß-amyloid PET for research purposes. Transaxial slices and Neurostat 3D-SSP analyses of 18 F-FDG PET and CBF-SPECT scans were independently reviewed by five nuclear medicine clinicians blinded to all other data. Operators selected the most likely diagnosis and their diagnostic confidence. Accuracy analysis used final diagnosis incorporating ß-amyloid PET as the reference standard. RESULTS: Clinicians reported high diagnostic confidence in 83% of 18 F-FDG PET compared to 67% for CBF-SPECT (P = 0.001). All reviewers showed individually higher accuracy using 18 F-FDG PET. Based on majority read, the combined area under the receiver operating characteristic curve in diagnosing AD was 0.71 for 18 F-FDG PET and 0.61 for CBF-SPECT (P = 0.02). The sensitivity of 18 F-FDG PET and CBF-SPECT was 76% versus 43% (P < 0.001), while specificity was 74% versus 83% (P = 0.45). CONCLUSIONS: 18 F-FDG PET is superior to CBF-SPECT in detecting AD among patients referred for the assessment of cognitive impairment.

Chronic ephedrine administration decreases brown adipose tissue activity in a randomised controlled human trial: implications for obesity.

AIMS/HYPOTHESIS: Brown adipose tissue (BAT) activation increases energy expenditure and may have therapeutic potential to combat obesity. The primary activating and adaptive signal for BAT is via ß-adrenergic signalling. We previously demonstrated that human BAT is acutely responsive to oral administration of the sympathomimetic, ephedrine. Here we aimed to determine whether adaptive thermogenesis can be induced via chronic treatment with ephedrine. METHODS: Twenty-three healthy young men, recruited from the general public in Melbourne, Australia, who were non-smokers, physically inactive and non-medicated with no prior history of cardiovascular disease or diabetes were recruited for this study. They were assigned to receive either 1.5 mg kg(-1) day(-1) ephedrine ('active' group; n = 12, age 23 ± 1 years, BMI 24 ± 1 kg/m(2)) or placebo (n = 11; 22 ± 2 years, 23 ± 2 kg/m(2)) for 28 days in a randomised (computer-generated random order sequence), placebo-controlled, parallel-group trial. Participants and all investigators were blinded to treatments. Body composition was measured before and after the intervention by dual energy X-ray absorptiometry. BAT activity, measured via (18)F-fluorodeoxyglucose positron emission tomography-computed tomography, in response to a single dose of 2.5 mg/kg ephedrine, was the primary outcome measure to be determined before and after the 28 day treatment period. RESULTS: Twenty-eight individuals were randomised and consented to the study. Twenty-three completed the trial and only these participants were included in the final analyses. After 28 days of treatment, the active group lost a significant amount of total body fat (placebo 1.1 ± 0.3 kg, ephedrine -0.9 ± 0.5 kg; p < 0.01) and visceral fat (placebo 6.4 ± 19.1 g, ephedrine -134 ± 43 g; p < 0.01), with no change in lean mass or bone mineral content compared with the placebo group. In response to acute ephedrine, BAT activity (change in mean standardised uptake value: placebo -3 ± 7%, ephedrine -22 ± 6%) and the increase in systolic blood pressure were significantly reduced (p < 0.05) in the active group compared with placebo. CONCLUSIONS/INTERPRETATION: Chronic ephedrine treatment reduced body fat content, but this was not associated with an increase in BAT activity. Rather, chronic ephedrine suppressed BAT glucose disposal, suggesting that chronic ephedrine treatment decreased, rather than increased, BAT activity. TRIAL REGISTRATION: ClinicalTrials.gov NCT02236962 FUNDING: This study was funded by the National Health and Medical Research Council of Australia Program Grant (1036352) and the OIS scheme from the Victorian State Government.

The prevalence of thyroglossal tract thyroid tissue on SPECT/CT following (131) I ablation therapy after total thyroidectomy for thyroid cancer.

OBJECTIVE: To determine the prevalence of thyroglossal tract thyroid tissue on SPECT/CT and to assess the contribution of this tissue to total neck radioactive iodine (RAI) activity in patients given (131) I ablation therapy after total thyroidectomy for thyroid cancer. PATIENTS AND METHODS: Eighty-three consecutive patients with thyroid cancer treated with total thyroidectomy underwent whole-body planar and SPECT/CT imaging of the neck following initial RAI ablation. On SPECT/CT, thyroglossal tract thyroid tissue was defined as RAI in the anterior neck, superior to the thyroid bed in close proximity to the midline without evidence of localization to lymph nodes. Quantification was performed using region of interest analysis on planar imaging following localization on SPECT/CT. SPECT/CT, and planar images were classified by two reviewers as positive, negative or equivocal with interobserver agreement quantified using a Kappa score. Disagreement was resolved using a third reviewer. RESULTS: Thyroglossal tract thyroid tissue was present in 39/83 (47%; 95%CI: 36-58%) patients on SPECT/CT. In these 39 patients, this tissue contributed to a significant amount of total neck activity (median = 50%; IQR 19-74%). Interobserver agreement for the presence of thyroglossal tract thyroid tissue was substantial on SPECT/CT (Kappa = 0.73) and fair on planar imaging (Kappa = 0.31). CONCLUSION: Thyroglossal tract thyroid tissue was present in one half of our study population and contributed to a significant amount of total neck RAI activity. Given the high prevalence of this tissue, our results suggest that total neck RAI activity on planar imaging may not be suitable to assess the completeness of thyroid bed surgery.

The GLP-1 receptor is expressed in vivo by human metastatic prostate cancer.

Objectives: The glucagon-like peptide-1 (GLP-1) receptor agonist, liraglutide, reduces human prostate cancer incidence, and similar GLP-1 receptor agonists reduce in vitro proliferation and in vivo growth of prostate cancer cell lines. Primary human prostate cancer expresses the GLP-1 receptor (GLP-1R) in vitro. Cancer evolves with stage, and whether advanced-stage human prostate cancer expresses GLP-1R is unknown. We hypothesised and aimed to prove that human metastatic castrate-resistant prostate cancer (mCRPC) expresses the GLP-1R in vivo. We hypothesised that mCRPC would thus be detectable by positron emission tomography/computed tomography (PET/CT) using a radiotracer bound to a GLP-1R ligand, as in exendin PET/CT. Materials and methods: Men with mCRPC, with more than one prostate-specific membrane antigen (PSMA)-avid lesion on PET/CT scanning (pathognomic in that setting for prostate cancer lesions), were approached to undergo PET/CT with gallium68-Dota-exendin-4. We documented PET/CT PSMA-avid lesions, which were also PET/CT exendin avid, as evidence of in vivo GLP-1R expression. Results: Out of the 24 men referred, three did not meet the inclusion criteria. Seventeen declined, largely because the study offered them no therapeutic benefit. Among the four men imaged, three had no exendin-avid lesions, while one had six osseous PSMA-avid lesions, three of which were also exendin avid. Conclusions: We demonstrated in vivo GLP-1R expression by human mCPRC, detecting PET/CT lesions avid for both PSMA and exendin, in one of four participants. GLP-1R expression may thus occur even in advanced-stage prostate cancer. Our data contribute to growing evidence supporting the testing of GLP-1 receptor agonists for therapeutic benefit in prostate cancer.

Comparison of contemporaneous left ventricular ejection fraction (LVEF) obtained from planar gated cardiac blood pool scans (GCBPS) and Tl-201 gated myocardial perfusion scans (MPS) using a novel solid state dedicated cardiac camera.

BACKGROUND: There is limited data on the concordance of left ventricular ejection fraction (LVEF) obtained via solid state dedicated cardiac cameras (SSD) and gated cardiac blood pool scans (GCBPS). This study aimed to examine the agreement of LVEF measured during GCBPS and Tl-201 myocardial perfusion scans (MPS) using SSD. METHODS: Seventy six patients were enrolled. Following stress MPS with 0.8 Mbq/kg (0.022 mCi/kg) Tl-201 and 8-frame gated rest studies after additional 15 Mbq (0.41 mCi) Tl-201, LVEFs were obtained using ECToolbox (ECT) and quantitative gated SPECT (QGS) software. Same day 16-frame planar GCBPS were performed. Interobserver variability was compared and LVEF results were compared using paired t tests, Pearson's correlation and the differences of the LVEF were plotted against GCBPS values. RESULTS: For GCBPS, ECT and QGS, the mean (±SD) LVEF was 52% ± 14%, 61% ± 18% and 48% ± 19%, respectively. When compared to GCBPS, ECT and QGS, LVEFs had similar R values of 0.85 and 0.83, respectively, and mean differences [95% limits of agreement (LA)] of -8.6% (-27.4% to +10.2%, P < .001) and 4.2% (-17.2% to +25.6%, P = .001), respectively. CONCLUSION: While the LVEF obtained by ECT or QGS demonstrates a statistically significant correlation with GCBPS, they are significantly different and the wide 95% LA suggest that Tl-201 MPS LVEFs derived from either software package are not interchangeable with GCBPS results.

Incidence and implications of negative serum thyroglobulin but positive I-131 whole-body scans in patients with well-differentiated thyroid cancer prepared with rhTSH or thyroid hormone withdrawal.

AIMS: To evaluate the incidence and clinical implications of a positive whole-body I-131 scan but negative stimulated serum Tg/TgAb level following an ablative or diagnostic I-131 dose in patients with well-differentiated thyroid cancer and whether there is a difference in incidence if prepared with thyroid hormone withdrawal compared with rhTSH stimulation. METHODS: I-131 scan findings, serum Tg/TgAb levels, TNM stage and method of thyroid tissue stimulation in 193 consecutive patients (138F, 55M) with well-differentiated thyroid cancer undergoing postoperative ablative I-131 therapy and 121 consecutive (94F, 27M) patients undergoing diagnostic I-131 surveillance scans were retrospectively reviewed. Comparisons of proportions were performed using Chi-square tests. Clinical, biochemical and I-131 scan follow-up data were obtained for each patient cohort. RESULTS: 39/193 (20·2%) postablative I-131 and 10/121 (8·3%) diagnostic I-131 patients had negative stimulated serum Tg/TgAb levels but positive I-131 scans for residual thyroid tissue. Nine (4·7%) of the postablative patients had I-131 uptake in the lateral neck suspicious for loco-regional metastatic disease. In the postablative I-131 group, 38/169 (22·5%) prepared with rhTSH compared to 1/24 (4·2%) prepared with thyroid hormone withdrawal were Tg/TgAb negative but I-131 scan positive (P = 0·04). Follow-up of 21/39 postablative I-131 patients with negative Tg/TgAb but positive I-131 scans confirmed a significant proportion of patients (4/21) (19·1%), remained Tg/TgAb negative/I-131 scan positive, some of whom had higher-risk disease at original diagnosis (2/4) (50%). CONCLUSIONS: Our study confirms that in the setting of I-131 ablation therapy or diagnostic I-131 scanning, a significant proportion of patients (20·2% and 8·3%, respectively) have residual benign or malignant thyroid tissue on whole-body scanning despite a negative stimulated serum Tg level. Whether such patients who would otherwise be missed as having residual thyroid tissue on serum Tg testing alone have a worse clinical outcome remains uncertain. Our findings do however suggest performing both stimulated serum Tg/TgAb levels and I-131 scans for the follow-up of patients with higher-risk thyroid cancer may be important. There may also be a slightly higher incidence of this phenomenon in patients prepared with rhTSH rather than by thyroxine withdrawal.

Optimal reproducibility of gated sestamibi and thallium myocardial perfusion study left ventricular ejection fractions obtained on a solid-state CZT cardiac camera requires operator input.

AIM: To evaluate the reproducibility of serial re-acquisitions of gated Tl-201 and Tc-99m sestamibi left ventricular ejection fraction (LVEF) measurements obtained on a new generation solid-state cardiac camera system during myocardial perfusion imaging and the importance of manual operator optimization of left ventricular wall tracking. METHODS: Resting blinded automated (auto) and manual operator optimized (opt) LVEF measurements were measured using ECT toolbox (ECT) and Cedars-Sinai QGS software in two separate cohorts of 55 Tc-99m sestamibi (MIBI) and 50 thallium (Tl-201) myocardial perfusion studies (MPS) acquired in both supine and prone positions on a cadmium zinc telluride (CZT) solid-state camera system. Resting supine and prone automated LVEF measurements were similarly obtained in a further separate cohort of 52 gated cardiac blood pool scans (GCBPS) for validation of methodology and comparison. Appropriate use of Bland-Altman, chi-squared and Levene's equality of variance tests was used to analyse the resultant data comparisons. RESULTS: For all radiotracer and software combinations, manual checking and optimization of valve planes (+/- centre radius with ECT software) resulted in significant improvement in MPS LVEF reproducibility that approached that of planar GCBPS. No difference was demonstrated between optimized MIBI/Tl-201 QGS and planar GCBPS LVEF reproducibility (P = .17 and P = .48, respectively). ECT required significantly more manual optimization compared to QGS software in both supine and prone positions independent of radiotracer used (P < .02). CONCLUSIONS: Reproducibility of gated sestamibi and Tl-201 LVEF measurements obtained during myocardial perfusion imaging with ECT toolbox or QGS software packages using a new generation solid-state cardiac camera with improved image quality approaches that of planar GCBPS however requires visual quality control and operator optimization of left ventricular wall tracking for best results. Using this superior cardiac technology, Tl-201 reproducibility also appears at least equivalent to sestamibi for measuring LVEF.

Noninvasive Assessment of Acute Graft-Versus-Host Disease of the Gastrointestinal Tract After Allogeneic Hemopoietic Stem Cell Transplantation Using 18F-FDG PET.

Acute graft-versus-host disease of the gastrointestinal tract (acute GIT-GVHD) often complicates allogeneic hemopoietic stem cell transplantation (AHSCT). 18F-FDG PET/CT is known to detect active inflammation and may be a useful noninvasive test for acute GIT-GVHD. The objective of this study was to evaluate the diagnostic utility of 18F-FDG PET/CT to noninvasively assess patients with clinically suspected acute GIT-GVHD. Fifty-one AHSCT patients with clinically suspected acute GIT-GVHD prospectively underwent 18F-FDG PET/CT scanning followed by upper and lower GIT endoscopy within 7 d. Endoscopic biopsies of 4 upper GIT and 4 colonic segments were obtained for histology to compare with corresponding quantitative segmental 18F-FDG PET/CT SUVmax Receiver-operating-characteristic curve (ROC) analysis was performed to determine predictive capacity of 18F-FDG PET/CT SUVmax for acute GIT-GVHD. A separate qualitative visual 18F-FDG PET/CT analysis was also performed for comparison. Results: Twenty-three of 51 (45.1%) patients had biopsy-confirmed acute GIT-GVHD, with 19 of 23 (82.6%) having upper GIT and 22 of 22 (100%) colonic involvement. One of 23 patients did not undergo a colonoscopy. GVHD involved the entire colon contiguously in 21 of 22 patients. For quantitative analysis, histology from 4 upper GIT and 4 colonic segments were compared with 18F-FDG PET/CT SUVmax Colonic segments positive for GVHD had a higher SUVmax (4.1 [95% CI, 3.6-4.5]) than did normal colonic segments (2.3 [1.9-2.7], P = 0.006). No difference was demonstrated in upper GIT segments. Quantitative 18F-FDG PET/CT yielded a 69% sensitivity, 57% specificity, 73% negative predictive value, and 59% positive predictive value for the detection of GVHD compared with 70%, 76%, 76%, and 68%, respectively, for qualitative analysis. Conclusion: 18F-FDG PET is a useful noninvasive diagnostic test for acute GIT-GVHD, which when present always involves the colon and usually in its entirety, suggesting colonic biopsy obtained by sigmoidoscopy is adequate for histologic confirmation when acute GIT-GVHD is suspected. Of note, 18F-FDG PET cannot distinguish acute GIT-GVHD from non-GVHD inflammatory changes in the colon.

Long-Term Follow-up and Outcomes of Retreatment in an Expanded 50-Patient Single-Center Phase II Prospective Trial of 177Lu-PSMA-617 Theranostics in Metastatic Castration-Resistant Prostate Cancer.

177Lu-PSMA-617 is a radioligand with high affinity for prostate-specific membrane antigen (PSMA), enabling targeted ß-irradiation of prostate cancer. We have previously reported favorable activity with low toxicity in a prospective phase II trial involving 30 men with metastatic castration-resistant prostate cancer. We now report their longer-term outcomes, including a 20-patient extension cohort and outcomes of subsequent systemic treatments after completion of trial therapy. Methods: Fifty patients with PSMA-avid metastatic castration-resistant prostate cancer who had progressed after standard therapies received up to 4 cycles of 177Lu-PSMA every 6 wk. Endpoints included prostate-specific antigen (PSA) response (Prostate Cancer Working Group 2), toxicity (Common Terminology Criteria for Adverse Events, version 4.03), imaging response, patient-reported health-related quality of life, progression-free survival, and overall survival. We also describe, as a novel finding, outcomes of men who subsequently progressed and had further systemic therapies, including 177Lu-PSMA. Results: Seventy-five men were screened to identify 50 patients eligible for treatment. Adverse prognostic features of the cohort included short median PSA doubling time (2.3 mo) and extensive prior treatment, including prior docetaxel (84%), cabazitaxel (48%), and abiraterone or enzalutamide (92%). The mean administered radioactivity was 7.5 GBq/cycle. A PSA decline of at least 50% was achieved in 32 of 50 patients (64%; 95% confidence interval [CI], 50%-77%), including 22 patients (44%; 95% CI, 30%-59%) with at least an 80% decrease. Of 27 patients with measurable soft-tissue disease, 15 (56%) achieved an objective response by RECIST 1.1. The most common toxicities attributed to 177Lu-PSMA were self-limiting G1-G2 dry mouth (66%), transient G1-G2 nausea (48%), G3-G4 thrombocytopenia (10%), and G3 anemia (10%). Brief Pain Inventory severity and interference scores decreased at all time points, including at the 3-mo follow-up, with a decrease of -1.2 (95% CI, -0.5 to -1.9; P = 0.001) and -1.0 (95% CI, -0.2 to -0.18; P = 0.013), respectively. At a median follow-up of 31.4 mo, median overall survival was 13.3 mo (95% CI, 10.5-18.7 mo), with a significantly longer survival of 18.4 mo (95% CI, 13.8-23.8 mo) in patients achieving a PSA decline of at least 50%. At progression after prior response, further 177Lu-PSMA was administered to 15 (30%) patients (median of 2 cycles commencing 359 d from enrollment), with a PSA decline of at least 50% in 11 patients (73%). Four of 21 patients (19%) receiving other systemic therapies on progression experienced a PSA decline of at least 50%. There were no unexpected adverse events with 177Lu-PSMA retreatment. Conclusion: This expanded 50-patient cohort of men with extensive prior therapy confirms our earlier report of high response rates, low toxicity, and improved quality of life with 177Lu-PSMA radioligand therapy. On progression, rechallenge 177Lu-PSMA demonstrated higher response rates than other systemic therapies.

Incidence of radiation thyroiditis and thyroid remnant ablation success rates following 1110 MBq (30 mCi) and 3700 MBq (100 mCi) post-surgical 131I ablation therapy for differentiated thyroid carcinoma.

OBJECTIVE: To evaluate the relationships between thyroid remnant (131)I uptake, radiation thyroiditis and remnant ablation success rate between lower (1110 MBq) and higher (3700 MBq) initial ablative (131)I dose for post-surgical ablation therapy for differentiated thyroid cancer. DESIGN: Patients having post-surgical administration of 1110 MBq (68 patients) or 3700 MBq (115 patients) (131)I were retrospectively reviewed. Thyroid remnant (131)I uptake on a 48 h post-administration scan was correlated with neck symptoms experienced. Patients were classified as having insignificant, mild or severe thyroiditis based on symptoms. Absent thyroid bed (131)I uptake on a follow-up 74 MBq (131)I study was considered successful ablation. RESULTS: 183 patients were included. Median (131)I remnant uptake was 37 MBq. 21% (39/183) of patients developed thyroiditis. Incidence and severity of thyroiditis increased with increasing remnant (131)I activity (P 73 MBq. For patients treated with 1110 MBq and 3700 MBq, incidence of thyroiditis was 12% and 27% (P = 0.02) and remnant ablation success rate was 76% and 84% (P = NS), respectively. Occurrence of thyroiditis did not correlate with successful ablation. CONCLUSIONS: Incidence and severity of radiation thyroiditis following (131)I remnant ablation therapy is directly related to thyroid remnant (131)I uptake. As 1110 MBq (131)I is associated with a significantly lower frequency of thyroiditis but similar remnant ablation rate to 3700 MBq, it warrants consideration for thyroid remnant ablation particularly in patients with low risk disease.

Double-blind, randomized, placebo-controlled study of high-dose HMG CoA reductase inhibitor therapy on ventricular remodeling, pro-inflammatory cytokines and neurohormonal parameters in patients with chronic systolic heart failure.

BACKGROUND: Statins decrease mortality in patients with coronary artery disease. However, chronic heart failure (CHF) patients were often excluded in such trials. Statins possess pharmacologic properties (independent of cholesterol lowering) that may be beneficial on ventricular remodeling in such patients. METHODS AND RESULTS: We conducted a 6-month randomized placebo (PBO)-controlled study of rosuvastatin (ROS) in patients with systolic (left ventricular ejection fraction [LVEF] <40%) CHF of ischemic or nonischemic etiology. The primary end point was change in LVEF by radionuclide ventriculogram. Secondary end points included change in echocardiographic parameters, neurohormonal and inflammatory markers, Packer composite score, death, and heart failure hospitalization. Patients were well matched for baseline values. Compared with PBO (n = 46), ROS patients (n = 40) had a decrease in low-density lipoprotein cholesterol (PBO +3, ROS -54%, P < .001). There was no significant change in LVEF by radionuclide ventriculogram (PBO +5.3, ROS +3.2%), fractional shortening by echocardiographic (PBO +2.7, ROS +1.8%), left ventricular end-diastolic diameter (PBO -1.7, ROS +0.8 mm), left ventricular end-systolic diameter (PBO -1.9, ROS +0.1 mm). Plasma norepinephrine, endothelin-1, brain natriuretic peptide, hsCRP, tumor necrosis factor-alpha and interleukin-6, patient global assessment, Packer composite, death/heart failure hospitalization, and adverse events were similar between PBO and ROS. CONCLUSIONS: Despite being safe and effective at decreasing plasma cholesterol, high-dose ROS did not beneficially alter parameters of LV remodeling. Reasons for absence of benefit are uncertain, but may include patient population studied, high dose of ROS used or high use of effective background CHF medications.

Findings on 18F-FDG PET scans after neoadjuvant chemoradiation provides prognostic stratification in patients with locally advanced rectal carcinoma subsequently treated by radical surgery.

UNLABELLED: Predicting outcome after aggressive therapy for advanced rectal cancer remains difficult. (18)F-FDG PET has emerged as a valid method for predicting patient outcomes after therapy in an increasing number of cancers. We evaluated the prognostic information obtained from the degree of change in tumor (18)F-FDG PET uptake induced by chemoradiation before radical curative surgery in patients with T3/T4 rectal cancer. METHODS: The study included 34 consecutive patients with T3/T4 Nx M0 rectal cancer on structural imaging, who underwent staging and postchemoradiation (18)F-FDG PET before planned curative surgery. Change in (18)F-FDG uptake was graded visually as complete (CMR), partial (PMR), or no (NoMR) metabolic response. Pre- and postchemoradiation (18)F-FDG PET-derived standardized uptake values (SUVs) were then obtained for PMR patients to determine whether SUV further stratified this subgroup. Operative findings were available in 30 patients (3 excluded because of (18)F-FDG PET-defined M1 disease, 1 refused surgery). Clinical status at study closeout (alive free from disease, FFD; alive with disease, AWD; or died of disease, DOD) was available for all patients. RESULTS: A pathologic complete response was found in only 6 of 30 patients (5 CMR, 1 false-positive PMR). However, after an estimated median 3.1 y of follow-up, all 17 CMR patients were FFD, 6 of 10 PMR patients were FFD, 2 of 10 had DOD, and 2 of 10 were AWD. All 3 NoMR patients DOD. PET response was highly significantly associated with overall survival duration (P < 0.0001) and time to progression (P < 0.0001). Pathologic complete response was the only other statistically significant prognostic factor (P < 0.03). The percentage of maximum SUV change after chemoradiation was not predictive of survival in PMR patients. CONCLUSION: Using a simple qualitative assessment, postchemoradiation (18)F-FDG PET scintigraphy provides good medium-term prognostic information in patients with advanced rectal cancer undergoing radical surgery with curative intent.

Ga-68 octreotate PET/CT and Tc-99m heat-denatured red blood cell SPECT/CT imaging of an intrapancreatic accessory spleen.

Intrapancreatic accessory spleens are relatively uncommon and can be difficult to distinguish from neuroendocrine tumours on CT, MRI and somatostatin receptor scintigraphy. We present the case of a 26-year-old woman with an incidentally diagnosed pancreatic lesion confirmed to be an intrapancreatic accessory spleen on Tc-99m heat-denatured red blood cell single photon emission computed tomography/CT.

Correlation of clinical outcomes with bremsstrahlung and Y-90 PET/CT imaging findings following Y-90 radiosynoviorthesis: a prospective study.

BACKGROUND: It is unclear how to predict which patients will respond to Y-90 radiosynoviorthesis. The aim of this study is to correlate clinical outcomes following Y-90 radiosynoviorthesis with bremsstrahlung and Y-90 PET/CT imaging findings. METHODS: Fifty-one joints underwent bremsstrahlung planar and Y-90 PET/CT imaging following Y-90 radiosynoviorthesis. The Y-90 distribution pattern on bremsstrahlung planar imaging was classified as diffuse or non-diffuse and compared with the intra or extra-articular location of activity on Y-90 PET/CT. Treatment response was assessed by patients and clinicians at 6 months. In patients who underwent bremsstrahlung SPECT, side-by-side comparison with PET was performed with image quality/resolution scored using a five-point-scale. FINDINGS: Bremsstrahlung planar images were classified as diffuse in 33/51 (65 %) and non-diffuse in 18/51 (35 %) scans. There was no association between treatment response and the bremsstrahlung planar imaging pattern. PET/CT confirmed an intra-articular location in all 33/33 (100 %) diffuse scans and an extra-articular location in 3/18 (17 %) non-diffuse scans. Of the three joints with extra-articular activity, none had any treatment response. Excluding these three joints, there remained no association between the bremsstrahlung planar imaging pattern and treatment response. Of the 42 joints imaged with SPECT, PET image quality/resolution was classified as superior in 40 (95 %). In one patient with extra-articular activity on PET/CT, SPECT/CT was unable to definitively localise the activity to the intra or extra-articular space. CONCLUSIONS: The distribution pattern on bremsstrahlung planar imaging did not correlate with clinical outcome following Y-90 radiosynoviorthesis in our study population. However, in patients with non-diffuse planar imaging patterns, Y-90 PET/CT should be considered to exclude extra-articular activity with PET providing superior image quality compared to SPECT.

The clinical impact of (18)F-FDG PET in patients with suspected or confirmed recurrence of colorectal cancer: a prospective study.

UNLABELLED: This prospective study aimed to confirm, in a clinical setting, the benefits suggested by earlier retrospective studies of (18)F-FDG PET scanning for the evaluation of patients with suspected recurrence of colorectal cancer. METHODS: The referring oncologist was asked to prospectively assign a treatment plan for 102 consecutive patients being evaluated by (18)F-FDG PET for suspected or confirmed recurrence of colorectal cancer and without evidence of unresectable disease on conventional staging investigations, including CT. This treatment plan was then compared with that based on incremental information supplied by PET. Management changes were validated by follow-up. RESULTS: For 6 patients, the oncologist would not commit to a management plan without access to PET information, and for all these patients, PET correctly guided management. Of the remaining 96 patients, the management plan for 54 (56%) was altered as a direct result of unexpected PET findings. Thus, PET directly influenced management in 60 (59%) of 102 patients. The discrepant PET results could be validated in 57 patients and were correct for both the presence and the extent of malignant disease in 52 (91%) of these patients but were false-positive in 1 patient because of a pelvic abscess and underestimated the extent of metastatic disease in 4 (7%). Relapse was confirmed in 49 (98%) of 50 evaluable patients with positive PET findings. Significantly, planned surgery was abandoned in 26 (60%) of 43 patients because of incremental PET findings. Of the 42 patients for whom management was not changed by PET findings, false-negative PET findings were documented for 5 (4 with metastases < 1 cm), and the PET findings for 1 were presumed to be false-positive because of sarcoidosis. CONCLUSION: This prospective study confirms the high impact, suggested by previous retrospective analyses, of (18)F-FDG PET on management of patients with suspected recurrent colorectal cancer. The major benefit of PET is avoidance of inappropriate local therapies by documentation of widespread disease.

Effect of mechanically simulated diaphragmatic respiratory motion on myocardial SPECT processed with and without attenuation correction.

UNLABELLED: The goal of this study was to assess the effect of diaphragmatic respiratory motion on inferior wall cold artifact in myocardial SPECT and to assess the ability of attenuation correction (AC) to correct for this artifact in the presence of diaphragmatic motion. METHODS: We used an anthropomorphic phantom with ventricular wall activity, variable ventricular caudal tilt, attenuating liver and spleen cold inserts, and variable vertical (diaphragmatic) motion amplitude and pattern. Cardiac SPECT images were acquired on a gamma camera with dual scanning transmission line sources and commercially available AC software (with scatter correction and iterative reconstruction). The acquired data were processed either using filtered backprojection or with the AC software. The resulting myocardial activity maps were processed with polar plots and with standardized inferior-to-anterior and anterior-to-lateral wall ratios. RESULTS: Subdiaphragmatic attenuation reduces inferior wall counts and this component of inferior wall artifact is fully corrected by AC relative to anterior wall counts both with and without diaphragmatic respiratory motion. In the phantom, diaphragmatic motion artifact manifests as reduction in relative count density in both the anterior wall and the inferior wall relative to the lateral wall, which is not corrected by AC. This artifact becomes more marked with increasing respiratory amplitude and its symmetry depends on the pattern of diaphragmatic motion. CONCLUSION: Images with AC acquired at small respiratory amplitudes (approximately 2 cm) in the phantom resemble images with AC found in published normal patient databases. These results support a clinical need for respiratory gating of myocardial SPECT images.