Fluorodeoxyglucose positron emission tomography for evaluating early response during neoadjuvant chemoradiotherapy in patients with potentially curable esophageal cancer.

BACKGROUND: Neoadjuvant chemoradiotherapy before surgery can improve survival in patients with potentially curable esophageal cancer, but not all patients respond. Fluorodeoxyglucose positron emission tomography (FDG-PET) has been proposed to identify nonresponders early during neoadjuvant chemoradiotherapy. The aim of the present study was to determine whether FDG-PET could differentiate between responding and nonresponding esophageal tumors early in the course of neoadjuvant chemoradiotherapy. METHODS: This clinical trial comprised serial FDG-PET before and 14 days after start of chemoradiotherapy in patients with potentially curable esophageal carcinoma. Histopathologic responders were defined as patients with no or less than 10% viable tumor cells (Mandard score on resection specimen). PET response was measured using the standardized uptake value (SUV). Receiver operating characteristic analysis was used to evaluate the ability of SUV in distinguishing between histopathologic responders and nonresponders. RESULTS: In 100 included patients, 64 were histopathologic responders. The median SUV decrease 14 days after the start of therapy was 30.9% for histopathologic responders and 1.7% for nonresponders (P = 0.001). In receiver operating characteristic analysis, the area under the curve was 0.71 (95% CI = 0.60-0.82). Using a 0% SUV decrease cutoff value, PET correctly identified 58 of 64 responders (sensitivity 91%) and 18 of 36 nonresponders (specificity 50%). The corresponding positive and negative predictive values were 76% and 75%, respectively. CONCLUSIONS: SUV decrease 14 days after the start of chemoradiotherapy was significantly associated with histopathologic tumor response, but its accuracy in detecting nonresponders was too low to justify the clinical use of FDG-PET for early discontinuation of neoadjuvant chemoradiotherapy in patients with potentially curable esophageal cancer.

Diagnostic strategies for pre-treatment staging of patients with oesophageal cancer.

BACKGROUND/AIMS: Current guidelines for staging oesophageal cancer recommend a series of preoperative investigations. There is no consensus on the recommended order for these investigations or whether all investigations are necessary in all patients. Our aim was to determine an efficient strategy for pre-treatment staging of patients with oesophageal cancer. METHODS: We retrospectively compared 15 staging strategies, based on all possible orders of all possible subsets of three staging modalities (computed tomography, endoscopic ultrasonography and external ultrasonography of the neck). We assumed that if distant metastases or local irresectability were found and confirmed, no further investigations would be performed. Main outcome was the minimal number of investigations needed to detect all patients with incurable disease. RESULTS: Using all three investigations in all 412 patients would lead to performance of 1,236 investigations. Both strategies starting with computed tomography or endoscopic ultrasonography and ending with external ultrasonography were most efficient, using a total of 1,112 investigations. CONCLUSION: The use of a conditional staging strategy with a specific order of imaging can reduce the number of tests necessary to identify incurable patients with oesophageal cancer by 10%. In our opinion, this is not enough to recommend implementation of a logistically more complex diagnostic system.

Response monitoring of neoadjuvant therapy using CT, EUS, and FDG-PET.

Neoadjuvant or adjuvant multimodality therapy in oesophageal cancer is introduced in an effort to improve prognosis. However, in a substantial fraction of patients there is no response to this non-surgical therapy. Non-invasive imaging modalities such as computed tomography (CT), endoscopic ultrasound (EUS) and 18F-2-fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET) have been evaluated for assessing patient response to therapy, and these are described in this review. Currently, FDG-PET seems to be the best available tool for neoadjuvant therapy response assessment in oesophageal cancer.

Radiopharmaceutical management of 90Y/111In labeled antibodies: shielding and quantification during preparation and administration.

BACKGROUND: The combined application of potent beta-emitting isotopes for therapy with remitting isotopes for scintigraphy requires a profound regimen concerning team member safety and radionuclide quantification. METHODS: We have developed materials and methods for a proper and easy manipulation of 90Y during preparation and administration of 90Y/111In pharmaceuticals used for radioimmunotherapy. RESULTS: The efficacy of the shielding measures is documented. Protocols for the calibration of gamma-dose calibrators with respect to 90Y are extended to the assessment of quench-corrected liquid scintillation counting of 90Y. The contribution of 90Y backscatter to 111 In counting is quantified. Newly developed shielding equipment allows an adequate administration of relatively large volumes (100 ml) of 90Y/111In labeled pharmaceuticals to patients. CONCLUSIONS: The procedures described combine pharmaceutical (Good Manufacturing Practice) and radiation safety requirements with an accurate logging of relevant data.

Role of positron emission tomography in the (re-)staging of oesophageal cancer.

BACKGROUND: Various studies have demonstrated that 18F-Fluorodeoxyglucose-positron emission tomography (FDG-PET), measuring altered tissue glucose metabolism, is a promising non-invasive method for detecting both distant nodal and haematogenous metastases in patients with oesophageal carcinoma (OC) and might thus prevent futile esophagectomy. Moreover, FDG-PET is a promising tool in assessing response to non-surgical treatment, and might therefore be used for an early decision on whether treatment should be stopped or continued. MATERIAL AND METHODS: Review of the recent literature regarding the diagnostic performance of FDG-PET in the preoperative staging of patients with OC and regarding diagnostic accuracy of FDG-PET in assessing response to neoadjuvant therapy in patients with OC compared to conventional techniques (especially computed tomography (CT) and endoscopic ultrasonography (EUS)). RESULTS: A search of the literature resulted in the inclusion of 16 studies on the diagnostic value of FDG-PET. Sensitivity and specificity for the detection of locoregional metastases were moderate. Sensitivity and specificity were reasonable for distant metastases. The diagnostic accuracy of FDG-PET in assessing response to treatment was similar to the accuracy of EUS, but significantly higher than that of CT. CONCLUSIONS: The staging value of FDG-PET in OC patients is limited in the detection of locoregional metastases; however; its value is higher in the detection of distant lymphatic and haematogenous metastases. Moreover, FDG-PET is a valuable tool for the non-invasive assessment of histopathologic tumour response after neoadjuvant therapy..

Synchronous primary neoplasms detected on 18F-FDG PET in staging of patients with esophageal cancer.

UNLABELLED: Because of improvements in diagnostic technology, the incidental detection of synchronous primary tumors during the preoperative work-up of patients with esophageal cancer has increased. The aim of this study was to determine the rate and clinical relevance of synchronous neoplasms seen on (18)F-FDG PET in staging of esophageal cancer. METHODS: From January 1996 to July 2004, 366 patients with biopsy-proven malignancy of the esophagus underwent (18)F-FDG PET for initial staging. This series of patients was retrospectively reviewed for the detection of synchronous primary neoplasms. RESULTS: Twenty synchronous primary neoplasms (5.5%) were identified in 366 patients. Eleven neoplasms were in the colorectum, 5 in the kidney, 2 in the thyroid gland, 1 in the lung, and 1 in the gingiva. One of the thyroid lesions and the lung lesion were erroneously interpreted as metastases, leading to incorrect upstaging of the esophageal tumor. CONCLUSION: (18)F-FDG PET detected unexpected synchronous primary neoplasms in 5.5% of patients with esophageal cancer. Sites of pathologic (18)F-FDG uptake should be confirmed by dedicated additional investigations before treatment, because synchronous neoplasms may mimic metastases.

In vivo prediction of response to antiestrogen treatment in estrogen receptor-positive breast cancer.

UNLABELLED: In metastatic breast cancer, the estrogen receptor (ER) is a well-known prognostic factor predictive of response to hormonal treatment in most, but not all, patients. Recently, a receptor-specific radioligand for in vivo imaging of the ER in breast cancer patients was developed: (123)I-labeled cis-11beta-methoxy-17alpha-iodovinyl-estradiol (Z-(123)I-MIVE). It showed high sensitivity and specificity for the in vivo detection of ER-positive breast cancer. The aim of this study was to determine whether Z-(123)I-MIVE scintigraphy is able to predict response or resistance to antiestrogen therapy in patients with metastatic ER-positive breast carcinoma. METHODS: Twenty-three patients with first metastases of their breast cancer and positive Z-(123)I-MIVE scintigraphy were included and treated with tamoxifen, 40 mg/d. Scintigraphy was repeated, on average, 4 wk later. The results of these scintigraphies were compared with the clinical outcome. RESULTS: On baseline scintigraphy, 21 of 23 patients had clear uptake and 2 of 23 patients had faint uptake of Z-(123)I-MIVE. After initiation of antiestrogen treatment, 17 of 21 patients with clear uptake on baseline scintigraphy showed complete blockade of ER activity on the Z-(123)I-MIVE scintigraphy. Four of 21 patients showed mixed or no ER blockade. All patients with faint baseline uptake or mixed or no ER blockade after tamoxifen showed progressive disease despite antiestrogen treatment. Patients with clear baseline uptake and complete ER blockade after tamoxifen had a significantly longer progression-free interval (mean +/- SEM, 14.4 +/- 1.6 vs. 1.8 +/- 0.8 mo; P < 0.01). CONCLUSION: Z-(123)I-MIVE scintigraphy seems to be a useful tool to predict response or resistance to antiestrogen treatment in ER-positive metastatic breast cancer patients and to depict nonresponders before the clinical manifestation of progression.

Lymphatic drainage routes of the gastric cardia visualized by lymphoscintigraphy.

UNLABELLED: This study was undertaken to assess the feasibility of lymphoscintigraphy of the gastric cardia and to identify the incidence of paraesophageal lymphatic drainage, precluding total gastrectomy with esophagojejunostomy as a potentially curative therapy for gastric cardia cancer. METHODS: Ten patients scheduled for esophagectomy with high-grade dysplasia or with esophageal cancer at least 3 cm above the esophagogastric junction were enrolled in this study. Preoperatively, 111 MBq of(99m)Tc-labeled nanocolloid (n = 5) or sulfur colloid (n = 5) were injected into the submucosa of the tumor-free cardia. Subsequently, lymphoscintigraphy in combination with CT was obtained. Locoregional lymph node stations were measured for radioactivity by a gamma-probe intraoperatively and ex vivo in the resection specimen. RESULTS: In each patient, at least 1 radioactive lymph node station was detected. In total, 42 radioactive lymph node stations were detected by gamma-probe. Of those 42 areas, 38 (90%) were visible at preoperative lymphoscintigraphy. In the group of 5 patients in whom nanocolloid was used, a median of 2 (range, 1-4) node stations per patient was identified, whereas when sulfur colloid was administered a median of 6 (range, 4-8) active lymph node stations per patient could be detected (P < 0.002). Paraesophageal drainage was identified in 1 patient. CONCLUSION: Lymphoscintigraphy of the gastric cardia is feasible and can accurately determine the location of radioactive lymph nodes. Early paraesophageal lymphatic drainage is rare.

Influence of ROI definition, partial volume correction and SUV normalization on SUV-survival correlation in oesophageal cancer.

OBJECTIVE: An explanation for the discrepancies in the reported correlations between standardized uptake value (SUV) and survival might be the application of different SUV methodologies. The primary aim of this study was to examine the influence of using different methodologies on SUV-survival correlation. METHODS: Data were used from a prospective cohort study consisting of oesophageal cancer patients in whom preoperative fluorodeoxyglucose positron emission tomography was performed. Various methodologies of SUV calculation/correction were correlated with the default (SUV A41% corrected for body surface area): different volume of interest definitions, different SUV normalization, with and without serum glucose correction, and with (PVC+ ) and without partial volume correction (PVC- ). Receiver operating characteristic (ROC) curves using any type of SUV for the identification of potential correlation with disease-free survival were also compared. RESULTS: Fifty-two patients were included for this study. Significant correlations were found between SUV A41% and all the other described SUVs: SUV 50% (r2=0.99; P< 0.001), SUV A50% (r2= 0.98; P< 0.001), SUVmax (r2= 0.98; P < 0.001), SUV A41% PVC+ (r2= 0.97; P < 0.001) and SUV A41% glucose (r2= 0.93; P <0.001). No correlation was found between volume of interest 41% and SUV A41%, with or without, PVC (P = 0.85 and P = 0.41). Significant correlations were found between SUVmax corrected for body surface area, SUVmax corrected for body weight (r2=0.96; P < 0.001) and SUV corrected for lean body mass (r2= 0.98; P < 0.001). ROC curves for various SUV methodologies showed an almost identical area under the curve for any type of SUV. CONCLUSION: A strong correlation was found between all the investigated SUV methodologies. Moreover, when looking for correlations between SUV and disease-free survival, the areas under the ROC curves were almost identical for any type of SUV methodology.

Patients' perception of diagnostic tests in the preoperative assessment of esophageal cancer.

OBJECTIVE: Defining an optimal staging strategy requires an evaluation of the effectiveness and costs of diagnostic tests and may include the burden of these tests for patients. This study evaluated the burden of cervical ultrasonography (US), endoscopic ultrasonography (EUS), computed tomography (CT) and positron emission tomography (PET) in patients with esophageal carcinoma (EC). METHODS: Consenting consecutive patients underwent a standard preoperative work-up. Burden of testing was evaluated with a self-report questionnaire addressing anxiety, embarrassment, and discomfort, each measured on a 1(none) to 5 (extreme) point-scale. An overall burden score was calculated by summing the three item scores. In addition, patients were asked to rank the four tests from least to most inconvenient. Statistical analysis was performed with nonparametric tests. RESULTS: 82 patients (67 , 15 ; mean age 64.3 yrs) participated. For most tests and most dimensions of burden, the large majority of subjects was in categories 1 and 2.With respect to anxiety, the rank order (from highest burden to lowest burden) was EUS, US, PET, and CT (average scores 1.7, 1.5, 1.4, and 1.2, respectively). For embarrassment, the rank order was EUS, PET, US, and CT (1.9, 1.5, 1.4, and 1.3 respectively). For discomfort, the rank order was EUS, PET, US and CT (2.0, 1.6, 1.4, and 1.2, respectively). And for total burden, the rank order was EUS, PET, US and CT (5.6, 4.6, 4.2, and 3.7). PET was ranked as least inconvenient by 35% of patients and as most inconvenient by 16% compared with the other tests. CONCLUSION: Significant but small differences were observed in patient burden for imaging tests to evaluate EC. The perceived burden of PET was lower than that of EUS, but higher than the burden of CT. However absolute values were low for all tests and therefore patient burden will not be a key feature for the construction of an optimal staging algorithm for EC.

18FDG uptake in oesophageal adenocarcinoma: linking biology and outcome.

PURPOSE: Variable uptake of 18FDG has been noticed in positron emission tomography (PET) studies of patients with oesophageal adenocarcinoma. The aim of the present study was to investigate biological parameters involved in 18FDG uptake in oesophageal adenocarcinoma for selection of patients with increased 18FDG uptake and prediction of prognostic value of 18FDG PET. PATIENTS AND METHODS: Preoperative PET scans were performed in 26 patients with histologically proven oesophageal adenocarcinoma. 18FDG uptake was semiquantitatively measured by SUV(BSAg. )Tumour sections were stained by immunohistochemistry for angiogenic markers (VEGF, CD31), glucose transporter-1 (Glut-1), hexokinase (HK) isoforms, for proliferation marker (Ki67), for macrophage marker (CD68) and for apoptosis marker (cleaved caspase-3). Cell densities, differentiation grade, degree of necrosis and mucus, T-stage and tumour size were assessed. In addition follow-up was analysed. RESULTS: No association was found between 18FDG uptake and angiogenic markers. In contrast, a significant correlation was found between 18FDG uptake and Glut-1 expression. No correlations were found between 18FDG uptake and HK isoforms, Ki67 or cleaved caspase-3. Also, no correlations were found between 18FDG uptake and cell density, differentiation grade, CD68, mucus and necrosis. However, there was a significant correlation between 18FDG uptake and tumour size and between 18FDG uptake and tumour recurrence. CONCLUSIONS: Glut-1 expression and tumour size seem parameters associated with 18FDG uptake in patients with biopsy proven oesophageal adenocarcinoma, and may be used to select oesophageal cancer patients in whom 18FDG-PET is of diagnostic value and may predict disease outcome.

NEOadjuvant therapy monitoring with PET and CT in Esophageal Cancer (NEOPEC-trial).

BACKGROUND: Surgical resection is the preferred treatment of potentially curable esophageal cancer. To improve long term patient outcome, many institutes apply neoadjuvant chemoradiotherapy. In a large proportion of patients no response to chemoradiotherapy is achieved. These patients suffer from toxic and ineffective neoadjuvant treatment, while appropriate surgical therapy is delayed. For this reason a diagnostic test that allows for accurate prediction of tumor response early during chemoradiotherapy is of crucial importance. CT-scan and endoscopic ultrasound have limited accuracy in predicting histopathologic tumor response. Data suggest that metabolic changes in tumor tissue as measured by FDG-PET predict response better. This study aims to compare FDG-PET and CT-scan for the early prediction of non-response to preoperative chemoradiotherapy in patients with potentially curable esophageal cancer. METHODS/DESIGN: Prognostic accuracy study, embedded in a randomized multicenter Dutch trial comparing neoadjuvant chemoradiotherapy for 5 weeks followed by surgery versus surgery alone for esophageal cancer. This prognostic accuracy study is performed only in the neoadjuvant arm of the randomized trial. In 6 centers, 150 consecutive patients will be included over a 3 year period. FDG-PET and CT-scan will be performed before and 2 weeks after the start of the chemoradiotherapy. All patients complete the 5 weeks regimen of neoadjuvant chemoradiotherapy, regardless the test results. Pathological examination of the surgical resection specimen will be used as reference standard. Responders are defined as patients with < 10% viable residual tumor cells (Mandard-score).Difference in accuracy (area under ROC curve) and negative predictive value between FDG-PET and CT-scan are primary endpoints. Furthermore, an economic evaluation will be performed, comparing survival and costs associated with the use of FDG-PET (or CT-scan) to predict tumor response with survival and costs of neoadjuvant chemoradiotherapy without prediction of response (reference strategy). DISCUSSION: The NEOPEC-trial could be the first sufficiently powered study that helps justify implementation of FDG-PET for response-monitoring in patients with esophageal cancer in clinical practice. TRIAL REGISTRATION: ISRCTN45750457.

Monitoring of response to pre-operative chemoradiation in combination with hyperthermia in oesophageal cancer by FDG-PET.

PURPOSE: To evaluate the use of positron emission tomography using 18F-fluorodeoxyglucose (FDG-PET) to assess early response to pre-operative chemoradiation therapy in combination with external locoregional hyperthermia in patients with oesophageal cancer by correlating the reduction of metabolic activity with histopathologic response. MATERIAL AND METHODS: Twenty-six patients with histopathologically proven intra-thoracic oesophageal cancer (with < or =2 cm gastric involvement), scheduled to undergo a 5-week course of pre-operative chemoradiation therapy and hyperthermia, were included. FDG-PET was performed before (n = 26) and 2 weeks after initiation of therapy (n = 17). FDG uptake was quantitatively assessed by standardized uptake values. RESULTS: After neoadjuvant therapy, 24 of the 26 patients underwent surgery. In 16 patients changes in FDG uptake were correlated to histopathologic response. In these patients, histopathologic evaluation revealed less than 10% viable tumour cells in eight patients (responders) and more than 10% viable tumour cells in eight patients (non-responders). In responders, FDG uptake decreased by a median -44% (-75 to 2); in non-responders, it decreased by a median of -15% (-46 to 40). At a threshold of 31% decrease of FDG uptake compared with baseline, sensitivity to detect response was 75%, with a corresponding specificity of 75%. The positive and negative predictive values were both 75%. CONCLUSION: FDG-PET is a promising tool for early response monitoring in patients undergoing chemoradiation therapy in combination with hyperthermia.

Esophageal cancer: CT, endoscopic US, and FDG PET for assessment of response to neoadjuvant therapy--systematic review.

PURPOSE: To compare diagnostic accuracy of computed tomography (CT), endoscopic ultrasonography (US), and fluorine 18 fluorodeoxyglucose (FDG) positron emission tomography (PET) for assessment of response to neoadjuvant therapy in patients with esophageal cancer by using a systematic review of the literature. MATERIALS AND METHODS: MEDLINE and EMBASE databases and Cochrane Database of Systematic Reviews were searched for relevant studies. Two reviewers independently assessed the methodological quality of each study. Summary receiver operating characteristic (ROC) analysis was used to summarize and compare the diagnostic accuracy of the three modalities. RESULTS: Four studies with CT, 13 with endoscopic US, and seven with FDG PET met inclusion criteria. Percentages of the maximum score in regard to methodological quality ranged from 15% to 100%. Summary ROC analysis could be performed for three studies with CT, four with endoscopic US, and four with FDG PET. The maximum joint values for sensitivity and specificity were 54% for CT, 86% for endoscopic US, and 85% for FDG PET. Accuracy of CT was significantly lower than that of FDG PET (P < .006) and of endoscopic US (P < .003). Accuracy of FDG PET and that of endoscopic US were similar (P = .839). In all patients, CT was always feasible, whereas endoscopic US was not feasible in 6% of the patients, and FDG PET was not feasible in less than 1%. CONCLUSION: CT has poor accuracy for assessment of response to neoadjuvant therapy in patients with esophageal cancer. Endoscopic US and FDG PET have equivalent good accuracy, but endoscopic US is not always feasible after chemotherapy and radiation therapy. FDG PET seems to be a promising noninvasive tool for assessment of neoadjuvant therapy in patients with esophageal cancer.

125I-BMIPP and 18F-FDG uptake in a transgenic mouse model of stunned myocardium.

Reported metabolic patterns in myocardial stunning are not uniform. We investigated relative myocardial perfusion, glucose and fatty acid uptake using a technetium-99 hexakis-2-methoxyisobutyl-isonitrile (MIBI), fluorine-18 2-fluoro-2-deoxyglucose (FDG) and iodine-125 15-(p-iodo-phenyl)-3(R,S)-methylpentadecanoic acid (BMIPP) mixture, in a recently developed transgenic (TR) mouse model which mimics stunned myocardium. Twenty-seven mice - 14 TR and 13 age-matched wild type controls (C) - were divided into four groups: TR-fed, TR-fasted, C-fed and C-fasted. Animals were sacrificed 2 h after injection, tissue samples counted and percent-injected dose/gram tissue (% id/g) calculated for each radioisotope. Tissues were also Folch extracted and 125I incorporation into the various lipid pools (TG, triglycerides; DG, diglycerides; FFA, free fatty acids; PL, phospholipids) was determined by thin-layer chromatography (TLC). The pooled data for each of the four groups (TR-fed vs C-fed and TR-fed vs C-fasted) showed no differences in myocardial blood flow (% MIBI id/g), glucose uptake (% FDG id/g) or fatty acid uptake (% BMIPP id/g). Only minor differences were observed in the incorporation of 125I-BMIPP into the myocardial TG, DG, FFA and PL lipid pools. However, significantly decreased myocardial FDG uptake was observed in a subset of fasted mice - four out of ten TR-fasted mice (3.4% vs 20.5% id/g) and three out of nine C-fasted mice (5.5% vs 30.6% id/g). The transgenic mouse model of stunned myocardium shows normal myocardial perfusion and overall intact myocardial glucose and myocardial fatty acid uptake as determined with clinically applicable radiolabelled analogues. These data are in line with the hypothesis that the contractile inefficiency in stunned myocardium is not linked to metabolic alterations but is associated with an insufficient chemical to mechanical energy coupling.

Safety and feasibility of cardiac FDG SPECT following oral administration of Acipimox, a nicotinic acid derivative: Comparison of image quality with hyperinsulinemic euglycemic clamping in nondiabetic patients.

BACKGROUND: Image quality of cardiac fluorine-18-deoxyglucose (FDG) studies is highly dependent on the metabolic conditions during the study; hyperinsulinemic euglycemic clamping ensures adequate image quality. However, the approach is time-consuming. Data in a small number of patients suggest that oral administration of a nicotinic acid derivative (Acipimox, 250 mg; Byk, The Netherlands) results in good image quality. METHODS AND RESULTS: The safety and image quality of cardiac FDG single photon emission computed tomography studies after Acipimox administration were evaluated (21 patients, group 2); the results were compared with studies performed during hyperinsulinemic euglycemic clamping (69 patients, group 1). Image quality was assessed visually and quantitatively with use of heart-to-lung, heart-to-liver, and myocardium-to-background ratios. Blood samples were drawn at baseline and at the time of FDG injection to determine levels of glucose, free fatty acids, and insulin. Baseline characteristics of group 1 and 2 patients were comparable. No side effects occurred in group 1. Four patients in group 2 (19%) had paroxysmal flushing. Image quality, assessed visually, was good in 100% of group 1 patients and in 86% of group 2 patients. Images were uninterpretable in only 1 patient in group 2 (5%). All quantitative parameters of image quality (heart-to-lung, heart-to-liver, and myocardium-to-background ratios) were comparable between group 1 and 2 patients. Baseline plasma levels of all substrates were comparable between groups. At the time of FDG injection, plasma levels of glucose and free fatty acids were comparable between groups; insulin was higher in group 1 patients. CONCLUSIONS: Cardiac FDG single photon emission computed tomography after Acipimox is a simple and safe approach that renders comparable image quality to that obtained during hyperinsulinemic euglycemic clamping.