Fluorine-18 Fluorodeoxyglucose PET Research Articles

Influence of the methodological aspects of the dichotomization of total metabolic tumor volume measured through baseline fluorine-18 fluorodeoxyglucose PET on survival prediction in lymphoma.

The total metabolic tumor volume (TMTV) measured from fluorine-18 fluorodeoxyglucose (18F-FDG) PET can be useful for determining the prognosis of patients with lymphoma. Stratifying patients into high- and low-TMTV risk groups requires a cutoff point, which is determined through the dichotomization method. This study investigated whether different TMTV dichotomization methods influenced survival prediction in patients with lymphoma. We retrospectively enrolled 129 patients with lymphoma who had undergone baseline 18F-FDG PET. TMTV was calculated using a fixed standardized uptake value threshold of 4.0. A total of six methods were employed to determine the optimal TMTV cutoff point using receiver-operating characteristic curve analyses, X-Tile bioinformatics software, and the Cutoff Finder web application. The prognostic performance of each method in survival prediction was examined. The median (interquartile range) TMTV was 123 cm3 (21-335 cm3). The optimal TMTV cutoff values for predicting progression-free survival (PFS) and overall survival (OS) were in the range of 144-748 cm3. The cutoff points were used to dichotomize patients into two groups with distinct prognoses. All TMTV dichotomizations were significantly predictive of PFS and OS. The survival curves showed significant differences between the high- and low-TMTV groups. The C-indices of the survival models did not significantly differ in any of the dichotomizations. The prognostic significance of TMTV was maintained regardless of the methodological aspects of dichotomization. However, the optimal TMTV cutoff point varied according to the chosen dichotomization method. Care should be taken when establishing an optimal TMTV cutoff point for clinical use.

Feasibility of somatostatin receptor-targeted imaging for detection of myocardial inflammation: A pilot study

BackgroundGallium-68 Dotatate binds preferentially to somatostatin receptor (sstr) subtype-2 (sstr-2) on inflammatory cells. We aimed at investigating the potential clinical use of sstr-targeted imaging for the detection of myocardial inflammation. MethodsThirteen patients, with suspected cardiac sarcoidosis (CS) based on clinical history and myocardial uptake on recent fluorine-18 fluorodeoxyglucose (FDG) PET, were enrolled to undergo Dotatate PET after FDG-PET (median time 37 days [IQR 25-55]). Additionally, we investigated ex-vivo the immunohistochemistry expression of sstr-2 in 3 explanted sarcoid hearts. ResultsAll FDG scans showed cardiac uptake (focal/multifocal = 6, focal on diffuse/heterogeneous = 7), and 46% (n = 6) extra-cardiac uptake (mediastinal/hilar). In comparison, Dotatate scans showed definite abnormal cardiac uptake (focal/multifocal) in 4 patients, probably abnormal (heterogenous/patchy) in 3, and negative uptake in 6 cases. Similarly, 6 patients had increased mediastinal/hilar Dotatate uptake. Overall concordance of FDG and Dotatate uptake was 54% in the heart and 100% for thoracic nodal activity. Quantitatively, FDG maximum standardized uptake value was 5.0 times [3.8-7.1] higher in the heart, but only 2.25 times [1.7-3.0; P = .019] higher in thoracic nodes relative to Dotatate. Ex-vivo, sstr-2 immunostaining was weakly seen within well-formed granulomas in all 3 examined sarcoid heart specimens with no significant staining of background myocardium or normal myocardium. ConclusionOur preliminary data suggest that, compared to FDG imaging, somatostatin receptor-targeted imaging may be less sensitive for the detection of myocardial inflammation, but comparable for detecting extra-cardiac inflammation.

Evaluation of the Small-animal Nano Scan PET/CT System using 89Zr.

The purpose of the present work was to evaluate the imaging characteristics of 89Zr-PET in comparison with those obtained using fluorine-18 Fluorodeoxyglucose (18FFDG) PET (a gold standard tracer in PET imaging) using a small-animal NanoScan PET/CT scanner. The system's spatial resolution, sensitivity, uniformity, and image quality were measured on a Nano Scan small-animal PET/CT scanner according to the NEMA NU4-2008 protocols. For reconstruction images, we used 2D and 3D reconstruction algorithms. The reconstruction methods included filter back projection (FBP), the ordered subsets expectation maximization (OSEM) algorithm, and the 3D Tera-Tomo algorithm, which are developed for the NanoScan small-animal PET/CT scanner. The results obtained showed a significant difference in the spatial resolution for 89Zr as compared to 22Na and 18F when using a 2D reconstruction algorithm. The spatial resolution values were much enhanced by using the 3D Tera-Tomo reconstruction for each isotope, the Full width at half maximum (FWHM) values was less than 1 for all isotopes at the center of the field of view (FOV). This difference in spatial resolution is dependent on the positron range, energy, and the reconstruction method. The long half-life of 89Zr makes it an ideal positron emitter for performing immuno- PET, which is matched with the biological half-life of intact mAbs.89Zr can also give several advantages over other long half-life positron emitters in relation to the overall imaging performance because of its relatively short positron range and simpler decay scheme. The values of 89Zr sensitivity that were obtained in the present study were less than those of previous studies.

FDG PET versus CT radiomics to predict outcome in malignant pleural mesothelioma patients

BackgroundCareful selection of malignant pleural mesothelioma (MPM) patients for curative treatment is of highest importance, as the multimodal treatment regimen is challenging for patients and harbors a high risk of substantial toxicity. Radiomics—a quantitative method for image analysis—has shown its prognostic ability in different tumor entities and could therefore play an important role in optimizing patient selection for radical cancer treatment. So far, radiomics as a prognostic tool in MPM was not investigated.Materials and methodsThis study is based on 72 MPM patients treated with surgery in a curative intent at our institution between 2009 and 2017. Pre-treatment Fluorine-18 fluorodeoxyglucose (FDG) PET and CT scans were used for radiomics outcome modeling. After extraction of 1404 CT and 1410 FDG PET features from each image, a preselection by principal component analysis was performed to include only robust, non-redundant features for the cox regression to predict the progression-free survival (PFS) and the overall survival (OS). Results were validated on a separate cohort. Additionally, SUVmax and SUVmean, and volume were tested for their prognostic ability for PFS and OS.ResultsFor the PFS a concordance index (c-index) of 0.67 (95% CI 0.52–0.82) and 0.66 (95% CI 0.57–0.78) for the training cohort (n = 36) and internal validation cohort (n = 36), respectively, were obtained for the PET radiomics model. The PFS advantage of the low-risk group translated also into an OS advantage. On CT images, no radiomics model could be trained. SUV max and SUV mean were also not prognostic in terms of PFS and OS.ConclusionWe were able to build a successful FDG PET radiomics model for the prediction of PFS in MPM. Radiomics could serve as a tool to aid clinical decision support systems for treatment of MPM in future.

Prognostic value of dual-point fluorine-18 fluorodeoxyglucose PET imaging, partial volume correction and glucose transporter-1 expression in resected nonsmall cell lung cancer patients.

To investigate the relationship between the prognosis and glucose transporter-1 (Glut-1) expression or fluorine-18 fluorodeoxyglucose uptake using partial volume correction and dual-point imaging in surgically resected nonsmall cell lung cancer (NSCLC) patients. Our patient population consisted of 108 NSCLC cases. The early maximum standardized uptake value (ESUVmax), delayed SUVmax (DSUVmax), partial volume correction SUVmax (cSUVmax) and retention index of primary lesions were calculated. Cox proportional hazard model was applied to evaluate the effects of PET parameters and Glut-1 expression. Overall survival (OS) and disease-free survival (DFS) were evaluated by Kaplan-Meier methods, and the difference in survival between subgroups was analyzed by log-rank test. On the Cox regression analysis, ESUVmax, DSUVmax, cSUVmax and Glut-1 were significantly related to DFS [ESUVmax, hazard ratio = 2.301, 95% confidential interval (CI) = 1.146-4.618, P = 0.019; DSUVmax, hazard ratio = 2.483, 95% CI = 1.257-4.905, P = 0.009; cSUVmax, hazard ratio = 2.205, 95% CI = 1.038-4.686, P = 0.04; Glut-1, hazard ratio = 2.095, 95% CI = 1.086-4.041, P = 0.001] and OS (ESUVmax, hazard ratio = 3.197, 95% CI = 1.339-7.633, P = 0.009; DSUVmax, hazard ratio = 3.599, 95% CI = 1.521-8.516, P = 0.004; cSUVmax, hazard ratio = 8.655, 95% CI = 2.048-36.658, P = 0.003; Glut-1, hazard ratio = 2.427, 95% CI = 5.140, P = 0.021). Retention index had no significant association with DFS or OS. On the Kaplan-Meier survival curves, the patients with high ESUVmax, DSUVmax, cSUVmax and Glut-1 showed significantly worse prognosis than those with low values (ESUVmax: DFS, P = 0.001, OS, P = 0.003; DSUVmax: DFS, P = 0.002, OS, P = 0.004; cSUVmax: DFS, P < 0.001, OS, P = 0.013; Glut-1: DFS, P = 0.012, OS, P = 0.002). cSUVmax, ESUVmax, DSUVmax and Glut-1 may be more useful biomarkers than retention index for predicting outcomes in NSCLC patients.

Prospective analysis of the utility of 18-FDG PET in Merkel cell carcinoma of the skin: A Trans Tasman Radiation Oncology Group Study, TROG 09:03.

TROG 09.03 prospectively studied the utility of Fluorine-18 Fluorodeoxyglucose (18-FDG) PET in the management of Merkel cell carcinoma of skin. Following consent and registration, a pre-treatment FDG-PET/CT was performed. Sites of avid disease were confirmed by cytology where practicable. Following surgery, patients with AJCCv7 Stages IIA-IIIB disease were treated with chemo-radiotherapy and reassessed with a post-treatment PET. Fifty-eight subjects (45 males and 13 females, median age 68years) were enrolled between 2011 and 2015, 43 patients of whom went on to receive chemo-radiotherapy. An occult primary was present in 22 (37.9%), T1 in 22 (37.9%) and T2 disease in 14 (24.1%). Nodal disease was present in 69% of cases. Fifty per cent of subjects had gross residual disease at the primary site and/or nodal site at the time of registration. 18-FDG PET/CT had a sensitivity of 94.74% (95% CI 82-99.3%) and a specificity of 88.24% (95% CI 63.56-98.54). The positive predictive value was 94.74% (83.01-98.51) and the negative predictive value was 88.24% (95% CI 65.81-96.69). The pre-treatment PET influenced a treatment decision in 27.6% of cases. Upstaging occurred in 15 (25.9%), with no down staging. Other diseases were identified in 4 (6.9%) patients. Univariate analysis failed to demonstrate that pre-treatment SUV levels or a negative post-treatment PET had any impact on overall survival. PET staged patients had 89% 3-year in-field loco-regional control and 76% 3-year overall survival. Staging 18-FDG-PET significantly influenced treatment decisions in approximately one-third of cases of MCC and should be considered in the routine pre-treatment work-up. Post-treatment PET was not found to be prognostic. Funding through the Medicare Benefits Schedule needs to be considered for high risk MCC.

Brain metabolic correlates of CSF Tau protein in a large cohort of Alzheimer’s disease patients: A CSF and FDG PET study

AimsPhysiopathological mechanisms of Alzheimer’s disease (AD) are still matter of debate. Especially the role of amyloid β and tau pathology in the development of the disease are still matter of debate. Changes in tau and amyloid β peptide concentration in cerebrospinal fluid (CSF) and hypometabolic patterns at fluorine-18 fluorodeoxyglucose (18F-FDG) PET scanning are considered as biomarkers of AD. The present study was aimed to evaluate the relationships between the concentrations of CSF total Tau (t-Tau), phosphorilated Tau (p-Tau) and Aβ1–42 amyloid peptide with 18F-FDG brain distribution in a group of patients with AD. Materials and methodsWe examined 131 newly diagnosed AD patients according to the NINCDS-ADRDA criteria and 20 healthy controls. The mean (±SD) age of the patients was 70 (±7) years; 57 were male and 74 were female. All patients and controls underwent a complete clinical investigation, including medical history, neurological examination, mini-mental state examination (MMSE), a complete blood screening (including routine exams, thyroid hormones and a complete neuropsychological evaluation). Structural MRI was performed not earlier than 1 month before the 18F-FDG PET/CT. The following patients were excluded: those with isolated deficits and/or unmodified MMSE (=25/30) on revisit (period of follow-up: 6, 12 and 18 months); patients who had had a clinically manifest acute stroke in the last 6 months with a Hachinsky score greater than 4; and patients with radiological evidence of subcortical lesions. All AD patients were taken off cholinesterase inhibitor treatment throughout the study. We performed lumbar puncture and CSF sampling for diagnostic purposes 2 weeks (±2 days) before the PET/CT scan. The relationship between brain F-FDG uptake and CSF biomarkers was analysed using statistical parametric mapping (SPM8; Wellcome Department of Cognitive Neurology, London, UK) implemented in Matlab R2012b using the MMSE score, sex and age, and other CSF biomarkers as covariates. Resultst-Tau, p-Tau and Aβ(1–42) in CSF resulted 774 ± 345 pg/ml, 98 ± 64 pg/ml and 348.8 ± 111 pg/ml respectively. SPM analysis showed a significant negative correlation between CSF t-Tau and 18F FDG uptake in right temporal, parietal and frontal lobe (Brodmann areas, BA, 20, 40 and 8; P fdr and few corr < 0.001, ke 19534). We did not find any significant relationships with other CSF biomarkers. Conclusionst-Tau deposition in brain is related to temporal, parietal and frontal hypometabolism in AD.

Molecular imaging using PET and SPECT for identification of breast cancer subtypes.

Breast cancer is a major disease with high morbidity and mortality in women. As a highly heterogeneous tumor, it contains different molecular subtypes: luminal A, luminal B, human epidermal growth factor 2-positive, and triple-negative subtypes. As each subtype has unique features, it may not be universal to the optimal treatment and expected response for individual patients. Therefore, it is critical to identify different breast cancer subtypes. Targeting subcellular levels, molecular imaging, especially PET and single photon emission computed tomography, has become a promising means to identify breast cancer subtypes and monitor treatment. Different biological processes between various subtypes, including changes correlated with receptor expression, cell proliferation, or glucose metabolism, have the potential for imaging with PET and single photon emission computed tomography radiopharmaceuticals. Receptor imaging, with radiopharmaceuticals targeting estrogen receptor, progesterone receptor, or human epidermal growth factor 2, is available to distinguish receptor-positive tumors from receptor-negative ones. Cell proliferation imaging with fluorine-18 fluorothymidine PET aids identification of luminal A and B subtypes on the basis of the correlation with the immunohistochemical biomarker Ki-67. Glucose metabolism imaging with fluorine-18 fluorodeoxyglucose PET may have potential to discriminate triple-negative subtypes from others. With increasing numbers of novel radiopharmaceuticals, noninvasive molecular imaging will be applied widely for the identification of different subtypes and provide more in-vivo information on individualized management of breast cancer patients.

Pharmacokinetics and microbiodistribution of 64Cu-labeled collagen-binding peptides in chronic myocardial infarction.

The aim of the study is to evaluate the pharmacokinetics and microbiodistribution of Cu-labeled collagen-binding peptides. The affinity constant (KD), association (ka), and dissociation rate constant (kd) for the peptide collagelin or its analog (named CRPA) binding to collagen were measured by biolayer interferometric analysis. Rats (n=4-5) with myocardial infarction or normal were injected intravenously with the Cu-labeled peptides or Cu-DOTA as a control. Dynamic PET imaging was performed for 60 min at 7-8 weeks after infarct. Fluorine-18 fluorodeoxyglucose PET imaging was performed to identify the viable myocardium. To validate the PET images, slices of heart samples from the base to the apex were analyzed using autoradiography and histology. The peptides bound to collagen with a KD of ∼0.9 µmol/l. The Cu-peptides and Cu-DOTA accumulated in the infarct area (confirmed by autoradiography and histology images) within 1 min of injection and were excreted rapidly through the renal system. The blood clearance curves were biphasic with elimination half-lives of 21.9±2.4, 26.2±4.6, and 21.2±2.1 min for Cu-CRPA, Cu-collagelin, and the control Cu-DOTA, respectively. The clearance half-lives from the focal fibrotic tissue (24.1±1.5, 25.6±8.0, and 21.4±1.3 min, respectively) and remote myocardium (20.8±0.7, 21.0±5.5, and 19.1±2.4 min, respectively) were not significantly different. The uptake ratios of infarct-to-remote myocardium (1.93±0.18, 2.15±0.38, and 1.88±0.08, respectively) for Cu-CRPA, Cu-collagelin, and Cu-DOTA remained stable for the time period between 10 and 60 min. The distribution of the Cu-collagelin probes corresponds to the heterogeneous distribution of expanded extracellular space in the setting of myocardial infarction. The overall washout rate from the fibrous tissue was determined by the slow washout rate (t1/2≥20 min) of the peptides from the extracellular space to the vasculature, not by the dissociation rate (t1/2<2 min) of the Cu-peptides from collagen.

Appropriate margin thresholds for isocontour metabolic volumetry of fluorine-18 fluorodeoxyglucose PET in sarcoma: a hybrid PET/MRI study.

Metabolic volumetry and heterogeneity indexes are increasingly being used in fluorine-18 fluorodeoxyglucose (F-FDG) PET, mostly using isocontour methods. However, there is no standard method to determine optimal margin thresholds for isocontour volume of interest (VOIiso). Here, VOIiso with various margin thresholds were compared with exact anatomical tumor volumes in sarcoma using a hybrid PET/MRI scanner. F-FDG PET/MRI images were retrospectively analyzed for 36 lesions of soft tissue or bone sarcoma. VOIiso of tumors was drawn with varying margin thresholds; standardized uptake value (SUV) 1.0-4.0 with an increment of 0.5 and 30-70% of maximal SUV (SUVmax) with an increment of 10%. Exact anatomical tumor volumes (VOIMRI) were drawn manually on the basis of MRI. In each VOI, metabolic tumor volume, SUVmean, total lesion glycolysis, and SD were measured and compared between VOIiso and VOIMRI. Significant correlations were observed between the indexes from VOIiso and VOIMRI. For metabolic tumor volume, no significant difference existed between VOIiso and VOIMRI with margin thresholds of 30 and 40% of SUVmax, and SUV 1.5. For SUVmean, no significant difference existed with 30% of SUVmax, and SUV 1.5. For total lesion glycolysis, no significant difference existed with 40% of SUVmax, SUV 1.5, and 2.0. For SD, no significant difference existed with 30% of SUVmax, SUV 1.5, and 2.0. Margin thresholds of 30 or 40% of SUVmax and SUV 1.5 or 2.0 may be used for the VOIiso method in F-FDG PET images of sarcoma. VOIiso with these margin thresholds are expected to produce reliable metabolic, volumetric, and heterogeneity indexes on F-FDG PET images.

The usefulness of fluorine-18 fluorodeoxyglucose PET in the detection of recurrence in patients with differentiated thyroid cancer with elevated thyroglobulin and negative radioiodine whole-body scan.

PET/computed tomography (CT) using fluorine-18 fluorodeoxyglucose (F-FDG) has been used in the diagnosis of recurrence and metastases of differentiated thyroid cancer (DTC) in cases of negative whole-body scan (WBS) despite elevated concentrations of stimulated thyroglobulin (Tg). To assess the utility of PET/CT in the detection of recurrence among patients with DTC with increased Tg levels and negative results of WBS. PET/CT results were retrospectively analyzed in patients with DTC with increased Tg and negative results of WBS as well as negative cervical ultrasonography and chest radiography. PET-CT was performed 1-2 weeks after recent diagnostics under conditions of endogenous or exogenous thyroid-stimulating hormone stimulation. PET/CT was performed using a Discovery ST scanner 1 h after an intravenously F-FDG injection (activity 4-5 MBq/kg). To determine the cutoff value of Tg, receiver operating characteristic curves were analyzed. Sixty-nine patients with DTC (48 women, 21 men) aged 22-83 years (mean 50.9±17.5 years) were qualified. In 44 patients (63.8%), PET/CT indicated lesions of DTC. Thirty (43.5%) patients had F-FDG positive findings. In the remaining 14 patients (20.3%), lesions were found in CT only. Patients with a positive PET/CT scan had significantly higher Tg values than patients with a negative PET/CT (mean 143.8 vs. 26.5 ng/ml, P=0.03). The cutoff value of Tg concentration measured with the receiver operating characteristic analysis was 32.9 ng/ml. PET/CT is a useful tool in the detection of recurrence among thyroid cancer patients in cases of conflicting results of standard procedures, particularly for those with high Tg levels and negative WBS. The probability of obtaining a positive PET-CT result increases with the level of Tg.

Novel assessment of global metabolism by 18F-FDG-PET for localizing affected lobe in temporal lobe epilepsy.

The aim of this study was to develop a novel method of global quantitative analysis for use in the diagnosis and treatment evaluation of temporal lobe epilepsy (TLE). We studied 16 patients diagnosed with TLE who underwent fluorine-18 fluorodeoxyglucose-PET (F-FDG-PET) and MRI at the Hospital of the University of Pennsylvania. To quantify temporal lobe hypometabolism, we averaged the mean standardized uptake value across regions of interest (ROIs) encompassing each lobe in its entirety and calculated the metabolic ratios and lateralization indices for each patient on the basis of global measurements. For comparison, we carried out a traditional 'punch biopsy' ROI analysis by averaging the mean standardized uptake value within 1 cm diameter ROIs across select slices. Both techniques were performed twice by the same rater to test intraobserver variability. An expert observer carried out visual analyses of both F-FDG-PET and MRI for reference. The global quantitative analysis identified a seizure focus lateralization in agreement with clinical evaluations for 91% of patients on both trials, with intraclass correlation coefficients of 0.97 and 0.92 for metabolic ratios and lateralization indices, respectively. The punch biopsy analysis was in agreement for 91 and 82% of patients on respective trials, with intraclass correlation coefficients of 0.90 and 0.75. Expert visual analyses carried out on F-FDG-PET and MRI were in agreement for 64 and 9% of patients, respectively. The global quantitative analysis proved to be the most accurate and reliable of the methods tested. This technique has the potential to improve metabolic analysis in TLE and other neuropsychiatric disorders.

Cerebral metabolic rate of glucose quantification with the aortic image-derived input function and Patlak method: numerical and patient data evaluation.

Quantitative maps of cerebral metabolic rate of glucose (CMRGlu) from fluorine-18 fluorodeoxyglucose-PET are useful in brain studies, but are challenging to acquire because of technical constraints, which hinder their use in clinical routine. Aortic image-derived input functions (IDIFs) combined with Sokoloff's method were proposed as a suitable solution. However, Sokoloff's method requires the use of standard kinetic constants, which may produce biased estimates. Patlak's method would be more appropriate, but concern can arise when used with an aortic IDIF from unavailability of a complete brain curve acquired starting from injection. The aim of this study was to develop a CMRGlu quantification technique that combines Patlak's method with aortic IDIFs in a clinical setting. A simple acquisition protocol for aortic IDIF measurement was developed and applied on a sample of patients with different degrees of hypometabolism (one healthy control, four patients with a neurodegenerative condition, and one coma patient). CMRGlu estimates in vivo were obtained with both the Sokoloff method and the Patlak method. Computer simulations were performed to assess the causes of bias affecting Sokoloff and Patlak estimates and interpret the results obtained in patients. Simulations showed that Sokoloff's method is less stable than Patlak's method as the extent of bias changed across different physiological states, potentially leading to misinterpretation of clinical data. In clinical patients, Sokoloff and Patlak estimates were correlated on the whole, but deviations emerged for critical physiological states. CMRGlu quantification with the Patlak method and aortic IDIF is feasible, easy to implement in clinical practice, and superior to Sokoloff's method from a personalized medicine perspective.

Granuloma Mimicking Local Recurrence on PET/CT after Liver Resection of Colorectal Liver Metastasis: A Case Report

Positron emission tomography–computed tomography (PET/CT) improves the diagnostic interpretation of fluorine-18 fluorodeoxyglucose (18F-FDG ) PET and CT in oncologic patients and has an impact on both diagnostic and therapeutic aspects of patient management. However, false positive findings from the PET/CT imaging should be taken into consideration as they mislead physicians into improper therapeutic actions. We present a 48-year-old female patient with a history of left colectomy for colorectal cancer and subsequent liver metastasectomy. After one year of follow-up, she presented with a highly suspicious lesion in the liver, which was confirmed on PET/CT as a metastatic liver tumor. Consequently, the patient underwent surgical excision of the tumor, and the definitive histological diagnosis showed a granulomatous tissue with giant cells and foreign body tissue reaction. Based on this report, we briefly review the dangerous pitfalls from radiological and PET/CT imaging concerning the preoperative diagnostic workup examination, as they may significantly alter the treatment plan in oncologic patients.

Feasibility of simultaneous 18F-FDG PET/MRI for the quantitative volumetric and metabolic measurements of abdominal fat tissues using fat segmentation.

Quantification of volume and inflammatory activity in the fat tissue is important because these are closely related to type 2 diabetes mellitus and cardiovascular disease. Fluorine-18 fluorodeoxyglucose (F-FDG) PET/computed tomography (CT) has been utilized to measure the metabolic activity of fat tissue. In this study, we assessed the feasibility of simultaneous PET/magnetic resonance (MR) in metabolic and volumetric measurements of fat tissue and the potential advantage over PET/CT. Twenty-four healthy individuals were enrolled, who underwent simultaneous F-FDG PET/MRI. Twenty-five F-FDG PET/CT scans were selected. Isocontour volumes of interest (VOIs) were used to segment and separate visceral fat (VF) and abdominal subcutaneous fat (SF) in using the MR image (T1 DIXON VIBE sequence) of PET/MR and the CT image of PET/CT. Volume, mean standardized uptake value of VF, and SF VOIs were calculated. Overlap between F-FDG PET and VF VOI was better in F-FDG PET/MR than PET/CT. The mean standardized uptake value of VF was associated with the degree of intestinal uptake on F-FDG PET/CT, but not on F-FDG PET/MR. Volumetric and metabolic measurements using F-FDG PET/MR showed an excellent reproducibility, with a high intraclass correlation coefficient between different observers (0.951-0.997). The measured metabolic activity was higher in VF than SF. We established a method for the quantitative measurement of volume and metabolic status of abdominal VF and SF using simultaneous F-FDG PET/MR. F-FDG PET/MR has an advantage over F-FDG PET/CT in terms of being less confounded by intestinal uptake. This method could be used to assess the inflammatory activity of fat tissue, which is a major risk factor for type 2 diabetes mellitus and cardiovascular disease.

Patient-derived tumor xenograft strategies for informed management of patients with metastatic melanoma.

Metastatic melanoma has benefited from immunotherapy and targeted therapy advances. Faced with the inescapable onset of treatment resistance, the choice of a second-line treatment can be guided by a patient-derived tumor xenograft (PDTX). This new approach requires an excellent multidisciplinary collaboration where the surgeon has a key role to play. Each patient included (stage IIIC or IV) presented with subcutaneous melanoma metastasis that could be surgically resected. The surgeon performed orthotopic PDTX on CB17-SCID mice. To validate the model, tumor material was amplified over three successive generations of animals to obtain cohorts compatible with carrying out a study to compare treatment response by targeted therapy (vemurafenib versus controls). Tumors were characterized (histologically and genetically) at all stages of the generations' amplification. Functional imaging by fluorine-18 fluorodeoxyglucose PET scan was performed for the third generation PDTX. Seventeen patients with a mutated BRAF V600E subcutaneous metastasis were included, yielding 257 PDTX. Clinical, histological, and genetic characteristics of the grafted tumors were stable over the three mice generations. The treatment response to vemurafenib was observed for all PDTX. The fluorine-18 fluorodeoxyglucose PET scan evidenced a decreased in glucose uptake in the treated tumors. PDTX models are being widely used in fundamental research and are more compatible with clinical issues. If PDTX are simple and easily reproducible in metastatic melanoma, an organized multidisciplinary platform is essential to implement them. In our experience, surgeons have a key role to play in the cohesion of this new therapeutic approach.

The prognostic value of tumor shadow disappearance rate on integrated PET/CT evaluation of solitary pulmonary nodules with low glucose metabolism.

This study aimed to determine the prognostic value of the tumor shadow disappearance rate (TDR) on integrated PET/computed tomography (PET/CT) evaluation of solitary pulmonary nodules (SPNs) with low glucose uptake. From January 2008 to September 2010, 99 patients who underwent fluorine-18 fluorodeoxyglucose PET (F-FDG-PET)/CT scanning for the evaluation of SPNs with a maximum standardized uptake value (SUVmax) below 2.75 (2.5+10%) were retrospectively reviewed. Among the 99 SPNs from these patients, 67 were malignant and 32 were benign, based on surgical pathology. Differences in baseline characteristics between the two groups were examined by means of the independent t-test, the Mann-Whitney U-test, and the χ-test. To test the efficacy of TDR for determining malignancy, the sensitivity, specificity, positive predictive value, negative predictive value, accuracy, and positive and negative likelihood ratios (LR+ and LR-, respectively) with 95% confidence intervals were calculated using the pathological test as the gold standard. Patients with malignant nodules were older than those with benign nodules (64.5 vs. 55.1 years, respectively, P<0.001) and had higher TDRs (0.8 vs. 0.3, respectively, P<0.001). The optimal cutoff point for the TDR was 0.4886 where the sensitivity, specificity, positive predictive value, and negative predictive value were 0.851, 0.844, 0.919, and 0.730, respectively, and the LR+ and LR- were 5.443 and 0177, respectively. A significant negative correlation between TDR and SUVmax was found only in the malignant group. The diagnostic value of TDR complements the PET/CT evaluation of SPNs with a low F-FDG uptake.

The role of fluorine-18 fluorodeoxyglucose PET in prognosis evaluation for stem cell transplantation of lymphoma: a systematic review and meta-analysis.

The role of fluorine-18 fluorodeoxyglucose PET (F-FDG PET) in prognostic evaluation of pre-stem cell transplantation (SCT) and post-SCT is still uncertain. A systematic review and meta-analysis were carried out to detect the prognostic power of F-FDG PET. 'PubMed', EMBASE, and Springer were searched for relevant articles. Subgroup analysis was carried out to evaluate the F-FDG PET in predicting the prognosis between Hodgkin lymphoma (HL) and non-Hodgkin lymphoma. Finally, 17 studies that included 1192 patients were eligible, 16 studies for progression-free survival (PFS) and 12 studies for overall survival (OS). For the pre-SCT PET or PET/computed tomography scan, the combined hazard ratios (HRs) of PET for PFS and OS were 2.32 and 2.64, respectively. Subgroup analysis showed that the HRs of PFS for HL and non-Hodgkin lymphoma were 3.28 and 2.00, respectively. For the post-SCT PET scan, the combined HR for PFS was 4.61. The sensitivity analysis showed that exlcusion of any single study had no significant effect on HR. We found that F-FDG PET was especially effective in predicting pre-STC and post-STC prognosis. The patients with a negative PET scan had a better prognosis compared with those with a positive scan in PFS and OS. In the subgroup analysis, F-FDG PET had a higher value in predicting prognosis before SCT for HL patients.

Mild-to-moderate hyperglycemia will not decrease the sensitivity of 18F-FDG PET imaging in the detection of pedal osteomyelitis in diabetic patients.

Pedal osteomyelitis is a worrisome complication of diabetic foot disease. Controlling serum glucose levels is difficult for many diabetic patients. High serum glucose levels could potentially affect the results of fluorine-18 fluorodeoxyglucose (18F-FDG) PET imaging in the detection of osteomyelitis. The aim of this investigation was to determine whether high serum glucose levels diminish the diagnostic accuracy of 18F-FDG PET imaging in detecting pedal osteomyelitis in diabetic patients. Forty-eight consecutive diabetic patients with a suspicion of pedal osteomyelitis were included in this investigation. At the time of 18F-FDG administration, 21 patients had serum glucose levels less than 150 mg/dl (group A), and 27 had serum glucose levels greater than 150 mg/dl (group B). Results of PET imaging were compared with final diagnostic outcome based on histopathology and/or 12 months' clinical follow-up. Osteomyelitis was confirmed in 17 patients. 18F-FDG PET correctly detected osteomyelitis in 15 of 17 patients for a sensitivity of 88.3% (15/17). This technique successfully excluded osteomyelitis in 30 of 31 cases for a specificity of 96.8% (30/31) and an overall accuracy of 93.8% (45/48). The sensitivity of 18F-FDG PET imaging was 87.5% (7/8) in patients with serum glucose levels less than 150 mg/dl (group A) and 88.9% (8/9) in patients with serum glucose levels greater than 150 mg/dl (group B). These results do not significantly differ from the overall sensitivity of 88.3% (15/17). Mildly to moderately elevated serum glucose levels do not adversely affect the accuracy of 18F-FDG PET imaging in the detection of pedal osteomyelitis in diabetic patients.

Evaluating the use of optimally respiratory gated 18F-FDG-PET in target volume delineation and its influence on radiation doses to the organs at risk in non-small-cell lung cancer patients.

This radiotherapy planning study evaluated tumour delineation using both optimally respiratory gated and nongated fluorine-18 fluorodeoxyglucose-PET (F-FDG-PET). For 22 non-small-cell lung tumours, both scans were used to create the nongated and gated (g) gross tumour volumes (GTVg) together with the accompanying clinical target volumes (CTV) and planning target volumes (PTV). The size of the target volumes (TV) was evaluated and the accompanying radiotherapy plans were created to study the radiation doses to the organs at risk (OAR). The median volumes of GTVg, CTVg and PTVg were statistically significantly smaller compared with the corresponding nongated volumes, resulting in a median TV reduction of 0.5 cm (interquartile range 0.1-1.2), 1.5 cm (-0.2 to 7.0) and 2.3 cm (-0.5 to 11.3) for the GTVg, CTVg and PTVg, respectively. For the OAR, only the percentage of lung (GTV included) receiving at least 35 Gy was significantly smaller after gating, with a median difference in lung volume receiving at least 35 Gy of 5.7 cm (interquartile range -0.8 to 30.50). Compared with nongated F-FDG-PET, the TVs obtained with optimally respiratory gated F-FDG-PET were significantly smaller, however, without a clinically relevant difference in radiation dose to the OAR.