Circulating Tumor DNA in Head and Neck Squamous Cell Carcinoma: Association with Metabolic Tumor Burden Determined with FDG-PET/CT.

BACKGROUND: The detection of circulating tumor DNA (ctDNA) with next-generation sequencing (NGS) in venous blood is a promising tool for the genomic profiling of head and neck squamous cell carcinoma (HNSCC). The association between ctDNA findings and metabolic tumor burden detected with FDG-PET/CT imaging is of particular interest for developing prognostic and predictive algorithms in HNSCC. METHODS: Twenty-six prospectively enrolled HNSCC patients were eligible for further analysis. All patients underwent tumor tissue and venous liquid biopsy sampling and FDG-PET/CT before definitive oncologic treatment. An NGS-based commercial panel was used for a genomic analysis of the samples. RESULTS: Maximum variant allele frequency (VAF) in blood correlated positively with whole-body (WB) metabolic tumor volume (MTV) and total lesion glycolysis (TLG) (r = 0.510, p = 0.008 and r = 0.584, p = 0.002, respectively). A positive liquid biopsy was associated with high WB-TLG using VAF ≥ 1.00% or ≥5.00% as a cut-off value (p = 0.006 or p = 0.003, respectively). Additionally, ctDNA detection was associated with WB-TLG when only concordant variants detected in both ctDNA and tissue samples were considered. CONCLUSIONS: A high metabolic tumor burden based on FDG imaging is associated with a positive liquid biopsy and high maximum VAF. Our findings suggest a complementary role of metabolic and genomic signatures in the pre-treatment evaluation of HNSCC.

PET-CT detection of local residual laryngeal carcinoma after definitive (chemo)radiotherapy.

BACKGROUND: Positron emission tomography and computed tomography (PET-CT) is currently recommended in evaluating the treatment response after (chemo)radiotherapy ([C]RT). In the larynx, post-treatment changes and physiological uptake make image interpretation more challenging compared to other head and neck sites. Previous research has not addressed imaging factors specifically in the larynx that would help in distinguishing the residual disease and explain the unique challenges of that anatomic area. The study cohorts are small and heterogenous. Our objective was to investigate the ability of PET-CT in diagnosing local residual laryngeal carcinoma, and to uncover imaging factors that could be used in differentiating the residual disease from post-treatment and physiological changes. In the same study cohort, we also aimed to uncover prognostic factors for local residual or recurrent disease. METHODS: Our retrospective study cohort included 73 patients with T2-T4 laryngeal carcinoma undergoing (C)RT with curative intention, and post-treatment non-contrast-enhanced PET-CT at 2-6 months. Findings were compared between local residual and non-residual disease. Local residual disease was defined as a persistent tumor growth with no evidence of remission in between, confirmed by biopsy, and evident within 6 months from the end of RT. PET-CT was evaluated using a 3-step scale: negative, equivocal, and positive. RESULTS: Nine (12%) had a local residual tumor and 11 (15%) developed local recurrence, based on the biopsy. The median follow-up of surviving patients was 64 months (range, 28-174). In univariate analysis, primary tumor diameter greater than 2.4 cm (median value), and vocal cord fixation were prognostic for local residual or recurrent disease. Sensitivity, specificity, PPV, and NPV were 100%, 75%, 36%, and 100%, respectively, when the equivocal interpretation was grouped with the positive interpretation. All local residuals, and 28% (18/64) non-residuals, had a primary tumor area SUVmax of over 4.0 (p < 0.001). CT showed a persistent mass at the primary tumor area in 56% of residuals, and in 23% of non-residuals (p > 0.05). By combining SUVmax>4.0 and mass, specificity improved to 91%. CONCLUSIONS: NPV of post-treatment PET-CT in laryngeal carcinoma is high, but equivocal and positive results have low PPV and require further diagnostics. All local residuals had SUVmax over 4.0. The combination of SUVmax over 4.0 and mass on CT increased specificity, but the sensitivity was low.

Pancreatic imaging in MEN1-comparison of conventional and somatostatin receptor positron emission tomography/computed tomography imaging in real-life setting.

OBJECTIVE: Pancreatic neuroendocrine tumors (panNETs) are the leading cause of death in patients with multiple endocrine neoplasia type 1 (MEN1). The role of somatostatin receptor positron emission tomography/computed tomography (SSTR PET/CT) in MEN1 has not been established. The aim was to assess pancreatic imaging in MEN1 in a real-life setting. DESIGN: Fifty-eight patients with MEN1 [median age 40 (range 16-72) years] underwent SSTR PET/CT imaging; either as a screening tool regardless of disease stage (n = 47) or to further characterize known panNETs (n = 11). SSTR PET/CT and matched conventional imaging were blindly analyzed. We assessed the findings and the impact of SSTR PET/CT during a median follow-up of 47 months. RESULTS: SSTR PET/CT detected three times as many panNETs as conventional imaging (P < .001). SSTR PET/CT altered the management of 27 patients (47%). Seven patients (12%) were referred for surgery, and five (9%) received systemic treatment. In 15/25 (60%) patients with no previous panNET (n = 22) or in remission after surgery (n = 3), SSTR PET/CT identified a panNET (n = 14) or recurrence (n = 1). In eight patients, SSTR PET/CT revealed a panNET not immediately visible on conventional imaging. During a median follow-up of 47 months, three became visible on conventional imaging, but none required intervention. When SSTR PET/CT was negative, no panNETs were identified on conventional imaging during 38 months of follow-up. CONCLUSIONS: SSTR PET/CT demonstrates high accuracy in the detection of panNETs and alters the clinical management in nearly half of the MEN1-patients. SSTR PET/CT enables timely diagnosis and staging of MEN1-related panNETs.

Incidence and Predictors of Atrial Fibrillation in Cardiac Sarcoidosis: A Multimodality Imaging Study.

BACKGROUND: In cardiac sarcoidosis (CS), the risk and predictors of new-onset atrial fibrillation (AF) are poorly known. OBJECTIVES: The authors evaluated the incidence and characteristics of AF in newly diagnosed CS. METHODS: The authors studied 118 patients (78 women, mean age 50 years) with AF-naive CS having undergone cardiac 18F-fluorodexoyglucose positron emission tomography (18F-FDG PET) at the time of diagnosis. Details of patient characteristics and medical or device therapy were collected from hospital charts. The PET scans were re-analyzed for presence of atrial and ventricular inflammation, and coincident cardiac magnetic resonance (CMR) studies and single-photon emission computed tomography (SPECT) perfusions were analyzed for cardiac structure and function, including the presence and extent of myocardial scarring. Detection of AF was based on interrogation of intracardiac devices and on ambulatory or 12-lead electrocardiograms. RESULTS: Altogether 34 patients (29%) suffered paroxysms of AF during follow-up (median, 3 years) with persistent AF developing in 7 patients and permanent AF in 4. The estimated 5-year incidence of AF was 55% (95% CI: 34%-72%) in the 39 patients with atrial 18F-FDG uptake at the time of diagnosis vs 18% (95% CI: 10%-28%) in the 79 patients without atrial uptake (P < 0.001). In cause-specific Cox regression analysis, atrial uptake was an independent predictor of AF (P < 0.001) with HR of 6.01 (95% CI: 2.64-13.66). Other independent predictors were an increased left atrial maximum volume (P < 0.01) and history of sleep apnea (P < 0.01). Ventricular involvement by PET, SPECT, or CMR was nonpredictive. Symptoms of AF prompted electrical cardioversion in 12 patients (35%). Three of the 34 patients (9%) experiencing AF suffered a stroke versus none of those remaining free of AF. CONCLUSIONS: In newly diagnosed CS, future AF is relatively common and associated with atrial inflammation and enlargement on multimodality cardiac imaging.

Adalimumab and sulfasalazine in alleviating sacroiliac and aortic inflammation detected in PET/CT in patients with axial spondyloarthritis: PETSPA.

AIM: Inflammatory signals in the sacroiliac (SI) joints and the aorta of patients with axial spondyloarthritis (axSpA) were graded by positron emission tomography/computed tomography (PET/CT) imaging before and after treatment with sulfasalazine (SSZ) or adalimumab (ADA). METHODS: Patients with axSpA, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) ≥ 4, were recruited. Disease-modifying antirheumatic drug-naïve patients started SSZ for 12 weeks, whereas those with prestudy treatment with or contraindication to SSZ commenced ADA for 16 weeks. In addition, those patients in the SSZ group with insufficient response commenced ADA for 16 weeks. 18F-fluorodeoxyglucose PET/CT was performed after inclusion and after treatment with SSZ and ADA. Maximum standardized uptake value (SUVmax) was assessed for the aorta and the SI joints, and maximal target-to-blood-pool ratio (TBRmax) only for the aorta. RESULTS: Among five SSZ patients, mean ± SD BASDAI was 4.7 ± 1.6 before and 3.5 ± 1.4 after treatment (p = .101). In 13 ADA patients, the BASDAI decreased from 5.4 ± 1.6 to 2.8 ± 2.2 (p < .001). Among the SSZ patients, SUVmax in SI joints decreased from 2.35 ± 0.55 to 1.51 ± 0.22 (-35.8%, p = .029). Aortic TBRmax decreased from 1.59 ± 0.43 to 1.26 ± 0.26 (-33.2%, p = .087). In the ADA patients, SUVmax in the SI joints was 1.92 ± 0.65 before and 1.88 ± 0.54 after treatment (-1.8%, p = .808) and TBRmax in the aorta 1.50 ± 0.60 before and 1.40 ± 0.26 after treatment (-6.7%, p = .485). CONCLUSIONS: Our small open-label study showed that SSZ may reduce PET-CT-detectable inflammation in the SI joints, with a trend towards a reduction in the aorta.

Prospective comparison of 18F-PSMA-1007 PET/CT, whole-body MRI and CT in primary nodal staging of unfavourable intermediate- and high-risk prostate cancer.

PURPOSE: To prospectively compare 18F-prostate-specific membrane antigen (PSMA)-1007 positron emission tomography (PET)/CT, whole-body magnetic resonance imaging (WBMRI) including diffusion-weighted imaging (DWI) and standard computed tomography (CT), in primary nodal staging of prostate cancer (PCa). METHODS: Men with newly diagnosed unfavourable intermediate- or high-risk PCa prospectively underwent 18F-PSMA-1007 PET/CT, WBMRI with DWI and contrast-enhanced CT within a median of 8 days. Six readers (two for each modality) independently reported pelvic lymph nodes as malignant, equivocal or benign while blinded to the other imaging modalities. Sensitivity, specificity and accuracy were reported according to optimistic (equivocal lesions interpreted as benign) and pessimistic (equivocal lesions interpreted as malignant) analyses. The reference standard diagnosis was based on multidisciplinary consensus meetings where available histopathology, clinical and follow-up data were used. RESULTS: Seventy-nine patients completed all the imaging modalities, except for one case of interrupted WBMRI. Thirty-one (39%) patients had pelvic lymph node metastases, which were detected in 27/31 (87%), 14/31 (45%) and 8/31 (26%) patients by 18F-PSMA-1007 PET/CT, WBMRI with DWI and CT, respectively (optimistic analysis). In 8/31 (26%) patients, only 18F-PSMA-1007 PET/CT detected malignant lymph nodes, while the other two imaging modalities were reported as negative. At the patient level, sensitivity and specificity values for 18F-PSMA-1007 PET/CT, WBMRI with DWI and CT in optimistic analysis were 0.87 (95%CI 0.71-0.95) and 0.98 (95%CI 0.89-1.00), 0.37 (95%CI 0.22-0.55) and 0.98 (95%CI 0.89-1.00) and 0.26 (95%CI 0.14-0.43) and 1.00 (95%CI 0.93-1.00), respectively. CONCLUSION: 18F-PSMA-1007 PET/CT showed significantly greater sensitivity in nodal staging of primary PCa than did WBMRI with DWI or CT, while maintaining high specificity. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov ID: NCT03537391.

Correlation of Somatostatin Receptor 1-5 Expression, [68Ga]Ga-DOTANOC, [18F]F-FDG PET/CT and Clinical Outcome in a Prospective Cohort of Pancreatic Neuroendocrine Neoplasms.

PURPOSE: The aim of this study was to correlate immunohistochemical (IHC) tissue levels of SSTR1-5 with the receptor density generated from [68Ga]Ga-DOTANOC uptake in a prospective series of NF-PNENs. METHODS: Twenty-one patients with a total of thirty-five NF-PNEN-lesions and twenty-one histologically confirmed lymph node metastases (LN+) were included in this prospective study. Twenty patients were operated on, and one underwent endoscopic ultrasonography and core-needle biopsy. PET/CT with both [68Ga]Ga-DOTANOC and [18F]F-FDG was performed on all patients. All histological samples were re-classified and IHC-stained with monoclonal SSTR1-5 antibodies and Ki-67 and correlated with [68Ga]Ga-DOTANOC and [18F]F-FDG PET/CT. RESULTS: Expression of SSTR1-5 was detected in 74%, 91%, 80%, 14%, and 77% of NF-PNENs. There was a concordance of SSTR2 IHC with positive/negative [68Ga]Ga-DOTANOC finding (Spearman's rho 0.382, p = 0.043). All [68Ga]Ga-DOTANOC-avid tumors expressed SSTR2 or SSTR3 or SSTR5. Expression of SSTR5 was higher in tumors with a low Ki-67 proliferation index (PI) (-0.353, 95% CI -0.654-0.039, p = 0.038). The mean Ki-67 PI for SSTR5 positive tumors was 2.44 (SD 2.56, CI 1.0-3.0) and 6.38 (SD 7.25, CI 2.25-8.75) for negative tumors. CONCLUSION: SSTR2 was the only SSTR subtype to correlate with [68Ga]Ga-DOTANOC PET/CT. Our prospective study confirms SSTR2 to be of the highest impact for SST PET/CT signal.

A Prospective Comparison of 18F-prostate-specific Membrane Antigen-1007 Positron Emission Tomography Computed Tomography, Whole-body 1.5 T Magnetic Resonance Imaging with Diffusion-weighted Imaging, and Single-photon Emission Computed Tomography/Computed Tomography with Traditional Imaging in Primary Distant Metastasis Staging of Prostate Cancer (PROSTAGE).

BACKGROUND: Computed tomography (CT) and bone scintigraphy (BS) are the imaging modalities currently used for distant metastasis staging of prostate cancer (PCa). OBJECTIVE: To compare standard staging modalities with newer and potentially more accurate imaging modalities. DESIGN, SETTING, AND PARTICIPANTS: This prospective, single-centre trial (NCT03537391) enrolled 80 patients with newly diagnosed high-risk PCa (International Society of Urological Pathology grade group ≥3 and/or prostate-specific antigen [PSA] ≥20 and/or cT ≥ T3; March 2018-June 2019) to undergo primary metastasis staging with two standard and three advanced imaging modalities. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The participants underwent the following five imaging examinations within 2 wk of enrolment and without a prespecified sequence: BS, CT, 99mTc-hydroxymethylene diphosphonate (99mTc-HMDP) single-photon emission computed tomography (SPECT)-CT, 1.5 T whole-body magnetic resonance imaging (WBMRI) using diffusion-weighted imaging, and 18F-prostate-specific membrane antigen-1007 (18F-PSMA-1007) positron emission tomography(PET)-CT. Each modality was reviewed by two independent experts blinded to the results of the prior studies, who classified lesions as benign, equivocal, or malignant. Pessimistic and optimistic analyses were performed to resolve each equivocal diagnosis. The reference standard diagnosis was defined using all available information accrued during at least 12 mo of clinical follow-up. Patients with equivocal reference standard diagnoses underwent MRI and/or CT to search for the development of anatomical correspondence. PSMA PET-avid lesions without histopathological verification were rated to be malignant only if there was a corresponding anatomical finding suspicious for malignancy at the primary or follow-up imaging. RESULTS AND LIMITATIONS: Seventy-nine men underwent all imaging modalities except for one case of interrupted MRI. The median interval per patient between the first and the last imaging study was 8 d (interquartile range [IQR]: 6-9). The mean age was 70 yr (standard deviation: 7) and median PSA 12 ng/mL (IQR:7-23). The median follow-up was 435 d (IQR: 378-557). Metastatic disease was detected in 20 (25%) patients. The imaging modality 18F-PSMA-1007 PET-CT had superior sensitivity and highest inter-reader agreement. The area under the receiver-operating characteristic curve (AUC) values for bone metastasis detection with PSMA PET-CT were 0.90 (95% confidence interval [CI]: 0.85-0.95) and 0.91 (95% CI: 0.87-0.96) for readers 1 and 2, respectively, while the AUC values for BS, CT, SPECT-CT, and WBMRI were 0.71 (95% CI: 0.58-0.84) and 0.8 (95% CI: 0.67-0.92), 0.53 (95% CI: 0.39-0.67) and 0.66 (95% CI: 0.54-0.77), 0.77 (95% CI: 0.65-0.89) and 0.75 (95% CI: 0.62-0.88), and 0.85 (95% CI: 0.74-0.96) and 0.67 (95% CI: 0.54-0.80), respectively, for the other four pairs of readers. The imaging method 18F-PSMA-1007 PET-CT detected metastatic disease in 11/20 patients in whom standard imaging was negative and influenced clinical decision making in 14/79 (18%) patients. In 12/79 cases, false positive bone disease was reported only by PSMA PET-CT. Limitations included a nonrandomised study setting and few histopathologically validated suspicious lesions. CONCLUSIONS: Despite the risk of false positive bone lesions, 18F-PSMA-1007 PET-CT outperformed all other imaging methods studied for the detection of primary distant metastasis in high-risk PCa. PATIENT SUMMARY: In this report, we compared the diagnostic performance of conventional and advanced imaging. It was found that 18F-prostate-specific membrane antigen-1007 positron emission tomography/computed tomography (18F-PSMA-1007 PET-CT) was superior to the other imaging modalities studied for the detection of distant metastasis at the time of initial diagnosis of high-risk prostate cancer. PSMA PET-CT also appears to detect some nonmetastatic bone lesions.

Prediction of the aggressiveness of non-functional pancreatic neuroendocrine tumors based on the dual-tracer PET/CT.

BACKGROUND: Predicting the aggressive behavior of non-functional pancreatic neuroendocrine tumors (NF-PNET) remains controversial. We wanted to explore, in a prospective setting, whether the diagnostic accuracy can be improved by dual-tracer functional imaging 68Ga-DOTANOC and 18F-FDG-PET/CT in patients with NF-PNETs. METHODS: Thirty-one patients with NF-PNET (90% asymptomatic) underwent PET-imaging with 18F-FDG and 68Ga-DOTANOC, followed by surgery (n = 20), an endoscopic ultrasonography and fine-needle biopsy (n = 2) or follow-up (n = 9). A focal activity on PET/CT greater than the background that could not be identified as physiological activity was considered to indicate tumor tissue. The imaging results were compared to histopathology. The mean follow-up time was 31.3 months. RESULTS: Thirty-one patients presented a total of 53 lesions (40 histologically confirmed) on PET/CT. Thirty patients had a 68Ga-DOTANOC-positive tumor (sensitivity 97%) and 10 patients had an 18F-FDG-positive tumor. In addition, one 68Ga-DOTANOC-negative patient was 18F-FDG-positive. 18F-FDG-PET/CT was positive in 19% (3/16) of the G1 tumors, 63% (5/8) of the G2 tumors and 1/1 of the well-differentiated G3 tumor. 68Ga-DOTANOC-PET/CT was positive in 94% of the G1 tumors, 100% of the G2 tumors and 1/1 of the well-differentiated G3 tumor. Two out of six (33%) of the patients with lymph node metastases (LN+) were 18F-FDG-positive. The 18F-FDG-PET/CT correlated with tumor Ki-67 (P = 0.021). Further, the Krenning score correlated with tumor Ki-67 (P = 0.013). 18F-FDG-positive tumors were significantly larger than the 18F-FDG-negative tumors (P = 0.012). 18F-FDG-PET/CT showed a positive predictive value of 78% in the detection of potentially aggressive tumors (G2, G3, or LN + PNETs); the negative predictive value was 69%. CONCLUSIONS: 18F-FDG-PET/CT is useful to predict tumor grade but not the LN+ of NF-PNETs. Patients with 18F-FDG-avid NF-PNETs should be referred for surgery. The 68Ga-DOTANOC-PET/CT also has prognostic value since the Krenning score predicts the histopathological tumor grade. TRIAL REGISTRATION: The study has been registered at ClinicalTrials.gov; Non-functional Pancreatic NET and PET imaging, NCT02621541.

MGMT Promoter Methylation and Parathyroid Carcinoma.

CONTEXT: Parathyroid carcinoma (PC) is extremely rare. Prognosis is poor, with no known evidence-based systemic therapies. We previously reported complete remission in a patient with metastasized parathyroid carcinoma and high tumor MGMT promoter methylation status who was treated with temozolomide. OBJECTIVE: To study MGMT promoter methylation status in an additional set of aggressive parathyroid tumors. DESIGN/SETTING: The study included 12 patients: 7 with sporadic and 5 with familial primary hyperparathyroidism (two of the latter carried a CDC73 gross deletion). Patient 9 is the previously described patient with PC and high MGMT methylation status. Her daughter (patient 12) had surgery for severe primary hyperparathyroidism due to atypical parathyroid adenoma during pregnancy. Eleven patients thus had PC and one had atypical parathyroid adenoma. MGMT promoter methylation status was determined from DNA extracted from primary (n = 10) or metastatic (n = 2) tumors. A mean methylation level >20% was considered high. Patient 11 had metastatic PC and received temozolomide cycles. RESULTS: Only the previously published patient (patient 9) had high tumor MGMT promoter methylation status. This was not a characteristic of the atypical parathyroid adenoma of the daughter (patient 12). Patient 11 (CDC73 intragenic deletion) has disseminated PC, low MGMT promoter methylation, and stable disease on follow-up after temozolomide treatment. CONCLUSION: High MGMT promoter methylation status seems rare in PC. However, as demonstrated in other neuroendocrine tumors, some patients with disseminated PC might benefit from temozolomide. Demonstration of high methylation status could be a predictor of positive response to temozolomide treatment.

Effect of blood glucose level on standardized uptake value (SUV) in 18F- FDG PET-scan: a systematic review and meta-analysis of 20,807 individual SUV measurements.

OBJECTIVES: To evaluate the effect of pre-scan blood glucose levels (BGL) on standardized uptake value (SUV) in 18F-FDG-PET scan. METHODS: A literature review was performed in the MEDLINE, Embase, and Cochrane library databases. Multivariate regression analysis was performed on individual datum to investigate the correlation of BGL with SUVmax and SUVmean adjusting for sex, age, body mass index (BMI), diabetes mellitus diagnosis, 18F-FDG injected dose, and time interval. The ANOVA test was done to evaluate differences in SUVmax or SUVmean among five different BGL groups (< 110, 110-125, 125-150, 150-200, and > 200 mg/dl). RESULTS: Individual data for a total of 20,807 SUVmax and SUVmean measurements from 29 studies with 8380 patients was included in the analysis. Increased BGL is significantly correlated with decreased SUVmax and SUVmean in brain (p < 0.001, p < 0.001,) and muscle (p < 0.001, p < 0.001) and increased SUVmax and SUVmean in liver (p = 0.001, p = 0004) and blood pool (p = 0.008, p < 0.001). No significant correlation was found between BGL and SUVmax or SUVmean in tumors. In the ANOVA test, all hyperglycemic groups had significantly lower SUVs compared with the euglycemic group in brain and muscle, and significantly higher SUVs in liver and blood pool. However, in tumors only the hyperglycemic group with BGL of > 200 mg/dl had significantly lower SUVmax. CONCLUSION: If BGL is lower than 200 mg/dl no interventions are needed for lowering BGL, unless the liver is the organ of interest. Future studies are needed to evaluate sensitivity and specificity of FDG-PET scan in diagnosis of malignant lesions in hyperglycemia.

Heterogeneity of myocardial 2-[18F]fluoro-2-deoxy-D-glucose uptake is a typical feature in cardiac sarcoidosis: a study of 231 patients.

Aims: The goal of the investigation was to evaluate whether a semi-quantitative method reflecting myocardial 2-[18F]fluoro-2-deoxy-D-glucose (FDG) uptake heterogeneity has added value in addition to visual analysis in the diagnosis of cardiac sarcoidosis (CS). Methods and results: This retrospective analysis included 271 consecutive patients suspected of CS attending cardiac positron emission tomography combined with computed tomography (PET-CT) at our institution between 2007 and 2013. Visual analysis of PET-CT and semi-quantitative analysis of heterogeneity [coefficient of variation (CoV)] of myocardial FDG uptake were performed. The presence of CS and initial symptoms were verified from patient data. The criteria for CS included histological verification from the myocardium or from an extracardiac site. Thirty cancer patients without cardiac disease were included as controls. CS was diagnosed in 48/231 (20.8%) of analysed patients. Of these, 13 (27.1%) had no extracardial signs of the disease and 30 (62.5%) had FDG positive mediastinal lymph nodes. Visual analysis of PET-CT identified 48.9% of the CS patients. We found a cut-off value of 0.184 for CoV to have the best accuracy to detect CS from a patient population with suspected CS (75.0% sensitivity and 51.4% specificity). Compared to controls, CoV identified CS patients with a good accuracy (68.8% sensitivity and 93.3% specificity). CS patients with FDG positive mediastinal lymph nodes had higher CoV than CS patients without lymph node involvement (0.282 vs. 0.208, P = 0.016). CS patients with more severe initial symptoms had a higher CoV than patients with more benign symptoms (0.283 vs. 0.195, P = 0.01). Conclusion: CoV provides a good addition to visual analysis of cardiac FDG PET-CT in diagnosis of CS. As a semi-quantitative measure, it reduces intra-observer variability. It also seems to indicate more severe disease, but to confirm this, prospective studies are needed.

F-18-fluorodeoxyglucose positron emission tomography-guided sampling of mediastinal lymph nodes in the diagnosis of cardiac sarcoidosis.

Histologic proof of granulomatous inflammation is prerequisite for the diagnosis of cardiac sarcoidosis (CS). Because of the limited sensitivity of endomyocardial biopsy (EMB), confirmation of sarcoidosis often has to be acquired from extracardiac biopsies. We set out to review our experience of F-18-fluorodeoxyglucose positron emission tomography (F-18-FDG PET) in guiding extracardiac tissue biopsies in suspected CS. We included in this work 68 consecutive patients with proved CS who had undergone cardiac F-18-FDG PET with (n = 57) or without whole-body imaging as part of initial diagnostic evaluation. Their hospital charts, imaging studies, and diagnostic biopsies were reviewed in retrospect. Whole-body PET images showed extracardiac foci of abnormally high F-18-FDG uptake in 39 of 57 patients, of whom 38 had involvement of mediastinal lymph nodes (MLN). Parallel F-18-FDG uptake was found in other lymph nodes (n = 10), lungs (n = 9), liver (n = 3), spleen (n = 2), and thyroid gland (n = 1). Adding the mediastinal findings at cardiac PET without whole-body imaging, abnormal F-18-FDG uptake in MLN was found in totally 43 of the 68 patients with CS (63%). Histology of systemic sarcoidosis was known at presentation of cardiac symptoms in 8 patients. Of the 60 patients with missing histology, 24 patients underwent mediastinoscopy for sampling of PET-positive MLN, most often (n = 20) after nondiagnostic EMB; microscopy revealed diagnostic noncaseating granulomatous inflammation in 24 of the 24 cases (sensitivity 100%). In the remaining 36 patients, sarcoidosis histology was confirmed by EMB (n = 30), by biopsy of lungs (n = 2) or peripheral lymph nodes (n = 2), or at autopsy (n = 1) or post-transplantation (n = 1). In conclusion, MLN accumulate F-18-FDG at PET in most patients with CS and provide a highly productive source for diagnostic biopsies either primarily or subsequent to nondiagnostic EMB.

Combining FDG-PET and 99mTc-SPECT to predict functional outcome after coronary artery bypass surgery.

AIMS: Single-photon emission computed tomography (SPECT) and positron emission tomography (PET) are suggested to improve clinical decision-making in ischaemic cardiomyopathy. Here, we present a unique cohort of patients who underwent nuclear medicine studies and cardiac magnetic resonance imaging (MRI) both before and 1 year after coronary artery bypass (CABG) surgery to assess benefit from surgery. METHODS AND RESULTS: Before CABG, we applied three quantitative techniques using (18)F-fluorodeoxyglucose-PET and (99m)technetium-tetrofosmin-SPECT with a software tool to measure defects with hypoperfused but viable and non-viable myocardium in 15 patients. One method used solely PET, two others combined PET and SPECT at different thresholds. As a reference, we used change in left-ventricular (LV) function and volume by MRI. Preoperatively, ischaemic but viable areas detected by the method with a 10% threshold combining PET-SPECT and the PET-only method correlated significantly with preoperative regional wall thickening (WT; P = 0.03 and P = 0.005, respectively). When compared with global functional outcome (change in LV ejection fraction) and LV remodelling (change in end-diastolic volume) 1 year postoperatively, no correlation appeared with preoperative PET- or PET-SPECT-derived viable or non-viable tissue. Neither was any correlation observable between local change in WT and local preoperative defect size evaluated by any of these three methods. CONCLUSION: Preoperatively, PET and PET-SPECT with 10% threshold detected dysfunctional myocardium, but all analysis methods failed to predict 1-year functional outcome assessed by MRI. In patients with three-vessel disease and heart failure, SPECT perfusion and PET viability study results show substantial heterogeneity; this should be considered when selecting patients for revascularization.

(99m)Technetium Sestamibi-(123)Iodine Scintigraphy Is More Accurate Than (99m)Technetium Sestamibi Alone before Surgery for Primary Hyperparathyroidism.

Objectives. Studies comparing outcome of single-(99m)Tc-methoxyisobutylisonitrile ((99m)Tc-sestamibi) and dual-tracer (99m)Tc-sestamibi scintigraphy in combination with (123)I before primary surgery of primary hyperparathyroidism (PHPT) are scarce. Methods. We compared (99m)Tc-sestamibi/(123)I and (99m)Tc-sestamibi in a single-centre retrospective series of 269 PHPT patients. The results were related to laboratory, surgical and histological findings. Results. (99m)Tc-sestamibi/(123)I and (99m)Tc-sestamibi were positive in 206 (76.6%) and 111 (41.3%) of 269 patients, respectively (P < 0.001). Accuracies for (99m)Tc-sestamibi/(123)I and (99m)Tc-sestamibi were 63.4% and 34.9%, respectively (96% CI, P < 0.001). Prevalence of multiglandular disease was 15.2%. In multiglandular disease, (99m)Tc-sestamibi/(123)I and (99m)Tc-sestamibi revealed 43.8 and 22.1% of pathological glands, respectively (P < 0.001). Cure rate was similar for patients with (191/206; 92.7%) and without (59 of 63; 93.7%) a positive (99m)Tc-sestamibi/(123)I finding. Duration of targeted surgery (one or two quadrants) was 21 and 15 minutes shorter than bilateral neck exploration, respectively (both P < 0.001). Higher serum calcium (P = 0.014) and PTH (P = 0.055) concentrations and larger tumours (P < 0.001) characterized the 206 patients with a positive preoperative scan who were cured by removal of a single adenoma. Conclusions. (99m)Tc-sestamibi/(123)I scintigraphy is more accurate than (99m)Tc-sestamibi before surgery of PHPT. However, outcome of surgery is not determined by scintigraphy alone.

Seasonal Temperature Changes Do Not Affect Cardiac Glucose Metabolism.

FDG-PET/CT is widely used to diagnose cardiac inflammation such as cardiac sarcoidosis. Physiological myocardial FDG uptake often creates a problem when assessing the possible pathological glucose metabolism of the heart. Several factors, such as fasting, blood glucose, and hormone levels, influence normal myocardial glucose metabolism. The effect of outdoor temperature on myocardial FDG uptake has not been reported before. We retrospectively reviewed 29 cancer patients who underwent PET scans in warm summer months and again in cold winter months. We obtained myocardial, liver, and mediastinal standardized uptake values (SUVs) as well as quantitative cardiac heterogeneity and the myocardial FDG uptake pattern. We also compared age and body mass index to other variables. The mean myocardial FDG uptake showed no significant difference between summer and winter months. Average outdoor temperature did not correlate significantly with myocardial SUVmax in either summer or winter. The heterogeneity of myocardial FDG uptake did not differ significantly between seasons. Outdoor temperature seems to have no significant effect on myocardial FDG uptake or heterogeneity. Therefore, warming the patients prior to attending cardiac PET studies in order to reduce physiological myocardial FDG uptake seems to be unnecessary.

FDG-PET/CT in the Assessment of Treatment Response after Oncologic Treatment of Head and Neck Squamous Cell Carcinoma.

BACKGROUND: In many centers, (18)F-fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) is used to monitor treatment response after definitive (chemo)radiotherapy [(C)RT] for head and neck squamous cell carcinoma (HNSCC), but its usefulness remains somewhat controversial. We aimed at assessing the accuracy of FDG-PET/CT in detecting residual disease after (C)RT. METHOD: All HNSCC patients with FDG-PET/CT performed to assess treatment response 10-18 weeks after definitive (C)RT at our institution during 2008-2010 were included. The patient charts were reviewed for FDG-PET/CT findings, histopathologic findings, and follow-up data. The median follow-up time for FDG-PET/CT negative patients was 26 months. RESULTS: Eighty-eight eligible patients were identified. The stage distribution was as follows: I, n = 1; II, n = 15; III, n = 17; IV, n = 55. The negative predictive value, positive predictive value, specificity, sensitivity, and accuracy of FDG-PET/CT in detecting residual disease were 87%, 81%, 94%, 65%, and 85%, respectively. The corresponding specific figures for the primary tumor site were 91%, 71%, 94%, 59%, and 86% and for the neck 93%, 100%, 100%, 75%, and 94%, respectively. CONCLUSIONS: In patients who have received definitive (C)RT for HNSCC, post-treatment FDG-PET/CT has good potential to guide clinical decision-making. Patients with negative scan can safely be followed up clinically only, while positive scan necessitates tissue biopsies or a neck dissection to rule out residual disease.

Nordic MCL3 study: 90Y-ibritumomab-tiuxetan added to BEAM/C in non-CR patients before transplant in mantle cell lymphoma.

The main objective of the MCL3 study was to improve outcome for patients not in complete remission (CR) before transplant by adding (90)Y-ibritumomab-tiuxetan (Zevalin) to the high-dose regimen. One hundred sixty untreated, stage II-IV mantle cell lymphoma patients <66 years received rituximab (R)-maxi-CHOP (cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisone) alternating with R-high-dose cytarabine (6 cycles total), followed by high-dose BEAM/C (bis-chloroethylnitrosourea, etoposide, cytarabine, and melphalan or cyclophosphamide) and autologous stem cell transplantation from 2005 to 2009. Zevalin (0.4 mCi/kg) was given to responders not in CR before transplant. Overall response rate pretransplant was 97%. The outcome did not differ from that of the historic control: the MCL2 trial with similar treatment except for Zevalin. Overall survival (OS), event-free survival (EFS), and progression-free survival (PFS) at 4 years were 78%, 62%, and 71%, respectively. For responding non-CR patients who received Zevalin, duration of response was shorter than for the CR group. Inferior PFS, EFS, and OS were predicted by positron emission tomography (PET) positivity pretransplant and detectable minimal residual disease (MRD) after transplant. In conclusion, positive PET and MRD were strong predictors of outcome. Intensification with Zevalin may be too late to improve the outcome of patients not in CR before transplant. This trial was registered at www.clinicaltrials.gov as #NCT00514475.

Autologous bone marrow mononuclear cell transplantation in ischemic heart failure: a prospective, controlled, randomized, double-blind study of cell transplantation combined with coronary bypass.

BACKGROUND: Bone marrow mononuclear cell (BMMC) transplantation for heart failure has shown inconsistent therapeutic efficacy. METHODS: We enrolled 104 ischemic heart failure patients scheduled for coronary artery bypass surgery (CABG). After 4- to 12-week pharmacotherapy optimization, 39 patients with left ventricular ejection fraction (LVEF) of ≤45% received injections of BMMC or vehicle intra-operatively into the myocardial infarction border area in a randomized, double-blind manner. RESULTS: The median number of cells injected was 8.4 × 10(8) (interquartile range [IQR]: 5.2 × 10(8) to 13.5 × 10(8)). We measured LV function and myocardial scar size by magnetic resonance imaging (MRI), and viability by positron emission tomography (PET) and single-photon emission computed tomography (SPECT), pre-operatively and after 1-year follow-up. LVEF, the pre-defined primary end-point measure, improved by a median of 5.6% in the control group (IQR 0.2 to 10.1) and by 4.8% in the BMMC group (IQR -0.5 to 8.2) (p = 0.59). Wall thickening in injected segments rose by a median of 4.5% among controls (IQR -18.1 to 23.9) and by 5.5% in the BMMC group (IQR -6.6 to 26.5) (p = 0.68). Changes in viability by PET and SPECT did not differ between groups. Myocardial scar size by MRI in injected segments rose by a median of 5.1% among controls (IQR -3.3 to 10.8), but fell by 13.1% in the BMMC group (IQR -21.4 to -6.5) (p = 0.0002). CONCLUSIONS: BMMC therapy combined with CABG failed to improve LV systolic function, or viability, despite reducing myocardial scar size.

[68Ga-DOTA-PET for neuroendocrine tumours]. / Somatostatiinireseptoreiden PET-TT-kuvaus 68Ga-DOTA-peptideillä parantaa neuroendokriinisten kasvainten diagnostiikkaa.

Neuroendocrine tumors (NET) are found in several organs and called NET tumors. They are relatively rare, most of them giving no symptoms and remaining undetected. Most NETs arise from the gut, stomach and bronchus. These tumors are diagnosed either by histology or by imaging. A typical feature of NETs is abundance of somatostatin receptors on the cell surface, which makes it possible to image the tumor by nuclear methods as well as estimate the response to treatment by somatostatin analogues ("theranostics"). In order to improve the diagnosis of NETs we started to produce 68Ga-DOTA peptides for PET.