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Showing papers in "European Journal of Nuclear Medicine and Molecular Imaging in 2014"


Journal ArticleDOI
TL;DR: 68Ga-PSMA PET/CT can detect lesions characteristic for PC with improved contrast when compared to standard 18F-fluoromethylcholine PET/ CT, especially at low PSA levels.
Abstract: Purpose Positron emission tomography (PET) with choline tracers has found widespread use for the diagnosis of prostate cancer (PC). However, choline metabolism is not increased in a considerable number of cases, whereas prostate-specific membrane antigen (PSMA) is overexpressed in most PCs. Therefore, a 68Ga-labelled PSMA ligand could be superior to choline tracers by obtaining a high contrast. The aim of this study was to compare such a novel tracer with standard choline-based PET/CT.

818 citations


Journal ArticleDOI
TL;DR: Tissue kinetics of a small molecule inhibitor of PSMA using PET/CT to estimate radiation dosimetry for the potential therapeutic use of 131I-MIP-1095 in men with mCRPC enables a targeted tumor therapy with unprecedented doses delivered to the tumor lesions.
Abstract: Introduction Since the prostate-specific membrane antigen (PSMA) is frequently over-expressed in prostate cancer (PCa) several PSMA-targeting molecules are under development to detect and treat metastatic castration resistant prostate cancer (mCRPC). We investigated the tissue kinetics of a small molecule inhibitor of PSMA ((S)-2-(3-((S)-1-carboxy-5-(3-(4-[124I]iodophenyl)ureido)pentyl)ureido)pentanedioicacid; MIP-1095) using PET/CT to estimate radiation dosimetry for the potential therapeutic use of 131I-MIP-1095 in men with mCRPC. We also report preliminary safety and efficacy of the first 28 consecutive patients treated under a compassionate-use protocol with a single cycle of 131I-MIP-1095.

314 citations


Journal ArticleDOI
TL;DR: PCa was detected more easily and more accurately with Ga-PSMA PET/MRI than with PET/CT and with lower radiation exposure, Consequently, this new technique could clarify unclear findings onPET/CT.
Abstract: Purpose 68Ga-labelled HBED-CC-PSMA is a highly promising tracer for imaging recurrent prostate cancer (PCa). The intention of this study was to evaluate the feasibility of PET/MRI with this tracer.

296 citations


Journal ArticleDOI
TL;DR: The first-in-human experience with 213Bi-DOTATOC targeted alpha therapy (TAT) in patients pretreated with beta emitters shows that TAT can induce remission of tumours refractory to beta radiation with favourable acute and mid-term toxicity at therapeutic effective doses.
Abstract: Purpose Radiopeptide therapy using a somatostatin analogue labelled with a beta emitter such as 90Y/177Lu-DOTATOC is a new therapeutic option in neuroendocrine cancer. Alternative treatments for patients with refractory disease are rare. Here we report the first-in-human experience with 213Bi-DOTATOC targeted alpha therapy (TAT) in patients pretreated with beta emitters.

276 citations


Journal ArticleDOI
TL;DR: Despite differing white and grey matter retention characteristics, cortical retention for each 18F tracer was highly correlated with that of PiB, enabling conversion of thresholds across tracer measurement scales with a high level of internal consistency.
Abstract: Purpose The increasing use of amyloid PET in Alzheimer’s disease research and clinical trials has motivated efforts to standardize methodology. We compared retention of the 11C radiotracer Pittsburgh Compound B (PiB) and that of two 18F amyloid radiotracers (florbetapir and flutemetamol) using two study populations. We also examined the feasibility of converting between tracer-specific measures, using PiB as the common link between the two 18F tracers.

234 citations


Journal ArticleDOI
TL;DR: 18F-Florbetapir PET may be a promising technique to image light chain and transthyretin cardiac amyloidosis and its role in diagnosing amyloids in other organ systems and in assessing response to therapy needs to be further studied.
Abstract: Cardiac amyloidosis, a restrictive heart disease with high mortality and morbidity, is underdiagnosed due to limited targeted diagnostic imaging. The primary aim of this study was to evaluate the utility of 18F-florbetapir for imaging cardiac amyloidosis. We performed a pilot study of cardiac 18F-florbetapir PET in 14 subjects: 5 control subjects without amyloidosis and 9 subjects with documented cardiac amyloidosis. Standardized uptake values (SUV) of 18F-florbetapir in the left ventricular (LV) myocardium, blood pool, liver, and vertebral bone were determined. A 18F-florbetapir retention index (RI) was computed. Mean LV myocardial SUVs, target-to-background ratio (TBR, myocardial/blood pool SUV ratio) and myocardial-to-liver SUV ratio between 0 and 30 min were calculated. Left and right ventricular myocardial uptake of 18F-florbetapir were noted in all the amyloid subjects and in none of the control subjects. The RI, TBR, LV myocardial SUV and LV myocardial to liver SUV ratio were all significantly higher in the amyloidosis subjects than in the control subjects (RI median 0.043 min−1, IQR 0.034 – 0.051 min−1, vs. 0.023 min−1, IQR 0.015 – 0.025 min−1, P = 0.002; TBR 1.84, 1.64 – 2.50, vs. 1.26, IQR 0.91 – 1.36, P = 0.001; LV myocardial SUV 3.84, IQR 1.87 – 5.65, vs. 1.35, IQR 1.17 – 2.28, P = 0.029; ratio of LV myocardial to liver SUV 0.67, IQR 0.44 – 1.64, vs. 0.18, IQR 0.15 – 0.35, P = 0.004). The myocardial RI, TBR and myocardial to liver SUV ratio also distinguished the control subjects from subjects with transthyretin and those with light chain amyloid. 18F-Florbetapir PET may be a promising technique to image light chain and transthyretin cardiac amyloidosis. Its role in diagnosing amyloid in other organ systems and in assessing response to therapy needs to be further studied.

227 citations


Journal ArticleDOI
TL;DR: F-FDG PET/CT is a useful tool for assessing organ involvement, monitoring therapeutic response, and guiding interventional treatment of IgG4-RD, and the image pattern is suggested to be updated into the consensus diagnostic criteria for IgG 4-RD.
Abstract: Purpose IgG4-related disease (IgG4-RD) is an increasingly recognized clinicopathological disorder with immune-mediated inflammatory lesions mimicking malignancies. A cohort study was prospectively designed to investigate the value of 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in characterizing IgG4-RD.

203 citations


Journal ArticleDOI
TL;DR: Pretherapy TMTV is an independent predictor of outcome in patients with DLBCL and shows independence of TMTV for OS prediction compared with other pretherapy indices of tumour burden, such as tumour bulk and the International Prognostic Index.
Abstract: Purpose We investigated the prognostic value of total metabolic tumour volume (TMTV) in diffuse large B-cell lymphoma (DLBCL).

179 citations


Journal ArticleDOI
TL;DR: The evidence strongly implies a correlation between the absorbed doses delivered and the response and toxicity, indicating that dosimetry-based personalized treatments would improve outcome and increase survival.
Abstract: Molecular radiotherapy (MRT) has demonstrated unique therapeutic advantages in the treatment of an increasing number of cancers. As with other treatment modalities, there is related toxicity to a number of organs at risk. Despite the large number of clinical trials over the past several decades, considerable uncertainties still remain regarding the optimization of this therapeutic approach and one of the vital issues to be answered is whether an absorbed radiation dose-response exists that could be used to guide personalized treatment. There are only limited and sporadic data investigating MRT dosimetry. The determination of dose-effect relationships for MRT has yet to be the explicit aim of a clinical trial. The aim of this article was to collate and discuss the available evidence for an absorbed radiation dose-effect relationships in MRT through a review of published data. Based on a PubMed search, 92 papers were found. Out of 79 studies investigating dosimetry, an absorbed dose-effect correlation was found in 48. The application of radiobiological modelling to clinical data is of increasing importance and the limited published data on absorbed dose-effect relationships based on these models are also reviewed. Based on National Cancer Institute guideline definition, the studies had a moderate or low rate of clinical relevance due to the limited number of studies investigating overall survival and absorbed dose. Nevertheless, the evidence strongly implies a correlation between the absorbed doses delivered and the response and toxicity, indicating that dosimetry-based personalized treatments would improve outcome and increase survival.

170 citations


Journal ArticleDOI
TL;DR: The outstanding response rates and survival outcomes suggest that PRRT is highly effective in advanced G1/2 pNET when compared to data of other treatment modalities.
Abstract: The clinical benefit of peptide receptor radionuclide therapy (PRRT) in patients with pancreatic neuroendocrine tumours (pNET) has not yet been well described and defined in its full extent due to limited data in this tumour subgroup. This study was intended to obtain robust, comparative data on the outcome and toxicity of standardized PRRT with 177Lu-octreotate in a well-characterized population of patients with advanced pNET of grade 1/2 (G1/2). We retrospectively analysed a cohort of 68 pNET patients with inoperable metastatic disease consecutively treated with 177Lu-octreotate (four intended cycles at 3-monthly intervals; mean activity per cycle 8.0 GBq). Of these 68 patients, 46 (67.6 %) had documented morphological tumour progression during the 12 months before initiation of treatment, and PRRT was the first-line systemic therapy in 35 patients (51.5 %). Response was evaluated according to modified Southwest Oncology Group (SWOG) criteria and additionally with Response Criteria in Solid Tumors (RECIST) 1.1. Survival was analysed using Kaplan-Meier curves and Cox proportional hazards model for univariate and multivariate analyses. Toxicity was assessed by standard follow-up laboratory work-up including blood count, and liver and renal function, supplemented with serial 99mTc-DTPA clearance measurements. The median follow-up period was 58 months (range 4 – 112). Reversible haematotoxicity (grade 3 or more) occurred in four patients (5.9 %). No significant nephrotoxicity (grade 3 or more) was observed. Treatment responses (SWOG criteria) consisted of a partial response in 41 patients (60.3 %), a minor response in 8 (11.8 %), stable disease in 9 (13.2 %), and progressive disease in 10 (14.7 %). Median progression-free survival (PFS) and overall survival (OS) were 34 (95 % CI 26 – 42) and 53 months (95 % CI 46 – 60), respectively. A G1 proliferation status was associated with longer PFS (p = 0.04) and OS (p = 0.044) in the multivariate analysis. Variables linked to impaired OS, on the other hand, were a reduced performance status (Karnofsky score ≤70 %, p = 0.007), a high hepatic tumour burden (≥25 % liver volume, p = 0.017), and an elevated plasma level of neuron-specific enolase (NSE >15 ng/ml, p = 0.035). The outstanding response rates and survival outcomes suggest that PRRT is highly effective in advanced G1/2 pNET when compared to data of other treatment modalities. Independent predictors of survival are the tumour proliferation index, the patient’s performance status, tumour burden and baseline plasma NSE level.

168 citations


Journal ArticleDOI
TL;DR: SPECT/CT significantly improved the specificity and positive predictive value of bone scintigraphy in cancer patients and had a significant effect on clinical management because of correct downstaging and upstaging, better definition of the extent of metastases, and a reduction in further diagnostic procedures.
Abstract: This study was designed to assess the additional value of SPECT/CT of the trunk used in conjunction with conventional nuclear imaging and its effects on patient management in a large patient series. In 353 patients, whole-body scintigraphy (WBS), SPECT, and SPECT/CT were prospectively performed for staging and restaging. SPECT/CT of the trunk was performed in all patients. In the 308 evaluable patients (211 with breast cancer, 97 with prostate cancer), clinical follow-up was used as the gold standard. Bone metastases were confirmed in 72 patients and excluded in 236. Multistep analyses per lesion and per patient were performed. Clinical relevance was expressed in terms of downstaging and upstaging rates on a per-patient basis. In the total patient group, sensitivities, specificities, and negative and positive predictive values on a per-patient basis were 93 %, 78 %, 95 % and 59 % for WBS, 94 %, 71 %, 97 % and 53 % for SPECT, and 97 %, 94 %, 97 % and 88 % for SPECT/CT, respectively. In all subgroups, specificity and positive predictive value were significantly (p < 0.01) better with SPECT/CT. Downstaging of metastatic disease in the total, breast cancer and prostate cancer groups using SPECT/CT was possible in 32.1 %, 33.8 % and 29.5 % of patients, respectively. Upstaging in previously negative patients by additional SPECT/CT was observed in three breast cancer patients (2.1 %). Further diagnostic imaging procedures for unclear scintigraphic findings were necessary in only 2.5 % of patients. SPECT/CT improved diagnostic accuracy for defining the extent of multifocal metastatic disease in 34.6 % of these patients. SPECT/CT significantly improved the specificity and positive predictive value of bone scintigraphy in cancer patients. In breast cancer patients, we found a slight increase in sensitivity. SPECT/CT had a significant effect on clinical management because of correct downstaging and upstaging, better definition of the extent of metastases, and a reduction in further diagnostic procedures.

Journal ArticleDOI
TL;DR: 18F-THK523 does not bind to Aβ in vivo, while following the known distribution of paired helical filaments (PHF)-tau in the brain, and selectively binds to tau in AD patients.
Abstract: Purpose Diagnosis of tauopathies such as Alzheimer’s disease (AD) still relies on post-mortem examination of the human brain. A non-invasive method of determining brain tau burden in vivo would allow a better understanding of the pathophysiology of tauopathies. The purpose of the study was to evaluate 18F-THK523 as a potential tau imaging tracer.

Journal ArticleDOI
TL;DR: Though clinical applications of quantitative SPECT imaging are lacking due to the previous non-availability of accurately calibrated SPECT reconstructions, these are beginning to emerge as the community and industry focus on producing SPECT/CT systems that are intrinsically quantitative.
Abstract: The introduction of combined modality single photon emission computed tomography (SPECT)/CT cameras has revived interest in quantitative SPECT. Schemes to mitigate the deleterious effects of photon attenuation and scattering in SPECT imaging have been developed over the last 30 years but have been held back by lack of ready access to data concerning the density of the body and photon transport, which we see as key to producing quantitative data. With X-ray CT data now routinely available, validations of techniques to produce quantitative SPECT reconstructions have been undertaken. While still suffering from inferior spatial resolution and sensitivity compared to positron emission tomography (PET) imaging, SPECT scans nevertheless can be produced that are as quantitative as PET scans. Routine corrections are applied for photon attenuation and scattering, resolution recovery, instrumental dead time, radioactive decay and cross-calibration to produce SPECT images in units of kBq.ml−1. Though clinical applications of quantitative SPECT imaging are lacking due to the previous non-availability of accurately calibrated SPECT reconstructions, these are beginning to emerge as the community and industry focus on producing SPECT/CT systems that are intrinsically quantitative.

Journal ArticleDOI
TL;DR: Measurement of baseline TMTV in lymphoma using a fixed 41% SUVmax threshold is reproducible and correlates with the other parameters for tumour mass evaluation, and should be evaluated in prospective studies.
Abstract: Purpose The presence of a bulky tumour at staging on CT is an independent prognostic factor in malignant lymphomas. However, its prognostic value is limited in diffuse disease. Total metabolic tumour volume (TMTV) determined on 18F-FDG PET/CT could give a better evaluation of the total tumour burden and may help patient stratification. Different methods of TMTV measurement established in phantoms simulating lymphoma tumours were investigated and validated in 40 patients with Hodgkin lymphoma and diffuse large B-cell lymphoma.

Journal ArticleDOI
TL;DR: TMTV0 is more relevant than tumour bulk for predicting the outcome in patients with HL, and adds a significant prognostic insight to interim PET response assessment, and may guide clinicians in their choice of therapeutic strategy.
Abstract: The presence of a bulky tumour at staging in Hodgkin lymphoma (HL) is a predictor of a poor outcome. The total metabolic tumour volume at baseline (TMTV0) computed on PET may improve the evaluation of tumour burden. To explore the clinical usefulness of TMTV0, we compared the prognostic value of TMTV0, tumour bulk and interim PET response in a retrospective single-centre study. From 2007 to 2010, 59 consecutive patients with a first diagnosis of HL were treated in our institution. PET was done at baseline (PET0) and after two cycles of chemotherapy (PET2), and treatment was not modified according to the PET2 result. TMTV0 was measured with a semiautomatic method using a 41 % SUVmax threshold. SUVmax reduction between PET0 and PET2 (ΔSUVmaxPET0-2) was also computed. Based on ROC analysis, patients with a ΔSUVmaxPET0-2 >71 % were considered good responders and a TMTV0 >225 ml was considered to represent hypermetabolic bulky disease. Median TMTV0 was 117 ml and 17 patients (29 %) had a TMTV0 >225 ml. TMTV0 (>225 ml vs. ≤225 ml) and tumour bulk ( 71 % and TMTV0 ≤225 ml (n = 37, 63 %), ΔSUVmaxPET0-2 = 225 ml (n = 17, 29 %), and ΔSUVmaxPET0-2 = 225 ml (n = 5, 8 %). In these three groups the 4-year PFS rates were 92 %, 49 %, and 20 % (p < 0.0001), respectively. TMTV0 is more relevant than tumour bulk for predicting the outcome in patients with HL, and adds a significant prognostic insight to interim PET response assessment. The combination of TMTV0 and ΔSUVmaxPET0-2 made it possible to identify three subsets of HL patients with different outcomes. This may guide clinicians in their choice of therapeutic strategy.

Journal ArticleDOI
TL;DR: Positive FDG PET/CT findings obviate the need for BMB for the detection of bone marrow involvement in patients with newly diagnosed DLBCL.
Abstract: To systematically review and meta-analyse published data on the diagnostic performance of 18F-FDG PET/CT in detecting bone marrow involvement in patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL). PubMed/MEDLINE and Embase were systematically searched for relevant studies. The methodological quality of each study was assessed. Sensitivities and specificities of FDG PET/CT in individual studies were calculated and meta-analysed with a random effects model. A summary receiver operating characteristic curve (sROC) was constructed with the Moses-Shapiro-Littenberg method. Weighted summary proportions of discrepancies between the FDG PET/CT and (blind) bone marrow biopsy (BMB) results among all patients were calculated. Seven studies, with a total of 654 patients with newly diagnosed DLBCL, were included. Overall, the quality of the included studies was moderate. The sensitivity and specificity of FDG PET/CT for detecting bone marrow involvement ranged from 70.8 % to 95.8 % and from 99.0 % to 100 %, with pooled estimates of 88.7 % (95 % confidence interval, CI, 82.5 – 93.3 %) and 99.8 % (95 % CI 98.8 – 100 %), respectively. The area under the sROC curve was 0.9983. The weighted summary proportion of FDG PET/CT-negative patients with positive BMB findings among all patients was 3.1 % (95 % CI 1.8 – 5.0 %) and the weighted summary proportion of FDG PET/CT-positive patients with negative BMB findings among all patients was 12.5 % (95 % CI 8.4 – 17.3 %). FDG PET/CT is accurate and complementary to BMB for detecting bone marrow involvement in patients with newly diagnosed DLBCL. A negative FDG PET/CT scan cannot rule out the presence of bone marrow involvement, but positive FDG PET/CT findings obviate the need for BMB for the detection of bone marrow involvement in these patients.

Journal ArticleDOI
TL;DR: qPET methodology provides semi-automatic quantification for interim FDG-PET response in lymphoma extending ordinal Deauville scoring to a continuous scale without need for follow-up data.
Abstract: Interim FDG-PET is used for treatment tailoring in lymphoma. Deauville response criteria consist of five ordinal categories based on visual comparison of residual tumor uptake to physiological reference uptakes. However, PET-response is a continuum and visual assessments can be distorted by optical illusions. With a novel semi-automatic quantification tool we eliminate optical illusions and extend the Deauville score to a continuous scale. SUVpeak of residual tumors and average uptake of the liver is measured with standardized volumes of interest. The qPET value is the quotient of these measurements. Deauville scores and qPET-values were determined in 898 pediatric Hodgkin’s lymphoma patients after two OEPA chemotherapy cycles. Deauville categories translate to thresholds on the qPET scale: Categories 3, 4, 5 correspond to qPET values of 0.95, 1.3 and 2.0, respectively. The distribution of qPET values is unimodal with a peak representing metabolically normal responses and a tail of clearly abnormal outliers. In our patients, the peak is at qPET = 0.95 coinciding with the border between Deauville 2 and 3. qPET cut values of 1.3 or 2 (determined by fitting mixture models) select abnormal metabolic responses with high sensitivity, respectively, specificity. qPET methodology provides semi-automatic quantification for interim FDG-PET response in lymphoma extending ordinal Deauville scoring to a continuous scale. Deauville categories correspond to certain qPET cut values. Thresholds between normal and abnormal response can be derived from the qPET-distribution without need for follow-up data. In our patients, qPET < 1.3 excludes abnormal response with high sensitivity.

Journal ArticleDOI
TL;DR: 18F-Fluorocholine PET/CT appears to be a promising, effective imaging method for localization of hyperfunctioning parathyroid tissue.
Abstract: Purpose Primary hyperparathyroidism is a common endocrine disorder which is diagnosed biochemically and for which therapy is surgical. A prerequisite for minimally invasive surgery, which minimizes morbidity and cost, is accurate localization of the involved gland(s). The aim of this study was to evaluate the usefulness of 18F-fluorocholine PET/CT for preoperative localization of hyperfunctioning parathyroid tissue.

Journal ArticleDOI
TL;DR: This case indicates the clinical utility of Ga-PSMA for the imaging of RCC and shows multiple pathological bone lesions with intense uptake of the tracer in the seventh cervical vertebra and acromion of the left scapula.
Abstract: Prostate-specific membrane antigen (PSMA) is a type II transmembrane protein with high expression in prostate carcinoma cells. Glu-NH-CO-NH-Lys-(Ahx)-[Ga(HBED-CC)] (GaPSMA) has been suggested as a novel tracer that can detect prostate carcinoma relapses and metastases with high contrast by targeting PSMA [1]. Besides prostate cancer, PSMA has been shown to be expressed in the neovasculature of various solid malignant tumours including clear cell renal cell carcinoma (ccRCC) [2, 3]. RCC is a potentially lethal cancer with aggressive behaviour, and has a propensity for distant metastatic spread. The common sites of metastases from ccRCC include lungs (33 – 72 %), intraabdominal lymph nodes (3 – 35 %) and brain (7 – 13 %) [4]. Bone metastases are also a frequent complication in patients with ccRCC [4]. We present to our knowledge the first reported case of a patient with a diagnosis of ccRCC with Ga-PSMA uptake. A 65-yearold woman, status post-nephrectomy, underwent GaPSMA (b) and F-FDG (a) PET/CT for staging. GaPSMA PET/CT showed multiple pathological bone lesions with intense uptake of the tracer in the seventh cervical vertebra and acromion of the left scapula (c, d, e; SUVmax=35 for PSMA, 7.2 for FDG), sternum (f, g, h; SUVmax=28.3 for PSMA, 5.15 for FDG), and right tuber ischiadicum (i, j, k; SUVmax 34.1 for PSMA, 5.3 for FDG). F-FDG PET/CT provided lower visual detectability of the bone metastasis. This case indicates the clinical utility of Ga-PSMA for the imaging of RCC.

Journal ArticleDOI
TL;DR: 89Zr-huJ591 PET imaging of prostate-specific membrane antigen expression is safe and shows good localization of disease in prostate cancer patients and 7 ± 1 days is the optimal imaging time.
Abstract: Purpose Given the bone tropism of prostate cancer, conventional imaging modalities poorly identify or quantify metastatic disease. 89Zr-huJ591 positron emission tomography (PET) imaging was performed in patients with metastatic prostate cancer to analyze and validate this as an imaging biomarker for metastatic disease. The purpose of this initial study was to assess safety, biodistribution, normal organ dosimetry, and optimal imaging time post-injection for lesion detection.

Journal ArticleDOI
TL;DR: The purpose of this work was to identify differences between these guidelines and suggest changes in both guidelines to achieve a level of harmonization.
Abstract: In 2008 the EANM published their paediatric dosage card. In 2011 the North American consensus guidelines recommended a set of administered activities for paediatric nuclear medicine. During the EANM congress in 2012 a working group of the EANM and the SNMMI met to study the possibility of harmonizing these guidelines. The purpose of this work was to identify differences between these guidelines and suggest changes in both guidelines to achieve a level of harmonization. In addition, the new version of the EANM paediatric dosage card (version 01.02.2014) is provided.

Journal ArticleDOI
TL;DR: The volume-based PET parameters (MTV and TLG) are significant prognostic factors for survival independent of tumour stage and better prognostic imaging biomarkers than SUVmax in patients with stage IIIA NSCLC after surgical resection.
Abstract: We evaluated the prognostic impact of volume-based assessment by 18F-FDG PET/CT in patients with stage III non-small-cell lung cancer (NSCLC). We reviewed 194 consecutive patients with stage IIIA NSCLC treated with surgical resection (surgical group) and 115 patients treated with nonsurgical therapy (nonsurgical group: 50 stage IIIA, 65 stage IIIB). Metabolic tumour volume (MTV), total lesion glycolysis (TLG), and maximum standardized uptake value (SUVmax) of primary tumours were measured using pretreatment 18F-FDG PET/CT. Overall survival was assessed using the Kaplan-Meier method. The prognostic significance of PET parameters and other clinical variables was assessed using Cox proportional hazards regression analyses. To evaluate and compare the predictive performance of PET parameters, time-dependent receiver operating characteristic (ROC) curve analysis was used. In the Cox proportional hazards models, MTV (HR = 1.27 for a doubling of MTV, P = 0.008) and TLG (HR = 1.22 for a doubling of TLG, P = 0.035) were significantly associated with an increased risk of death after adjusting for age, gender, histological cell type, T stage, N stage, and treatment variables in the surgical group. SUVmax was not a significant prognostic factor in either the surgical or nonsurgical group. In the time-dependent ROC curve analysis, volume-based PET parameters predicted survival better than SUVmax. The volume-based PET parameters (MTV and TLG) are significant prognostic factors for survival independent of tumour stage and better prognostic imaging biomarkers than SUVmax in patients with stage IIIA NSCLC after surgical resection.

Journal ArticleDOI
TL;DR: FDG circulation times and prescan blood glucose levels significantly affect FDG uptake in the aortic and carotid walls and may bias the results of image interpretation in patients undergoing vascular FDG PET/CT.
Abstract: 18F-FDG PET is increasingly used for imaging of vessel wall inflammation. However, limited data are available on the impact of methodological variables, i.e. prescan fasting glucose, FDG circulation time and injected FDG dose, and of different FDG uptake parameters, in vascular FDG PET imaging. Included in the study were 195 patients who underwent vascular FDG PET/CT of the aorta and the carotids. Arterial standardized uptake values (meanSUVmax), target-to-background ratios (meanTBRmax) and FDG blood-pool activity in the superior vena cava (SVC) and the jugular veins (JV) were quantified. Vascular FDG uptake values classified according to the tertiles of prescan fasting glucose levels, the FDG circulation time, and the injected FDG dose were compared using ANOVA. Multivariate regression analyses were performed to identify the potential impact of all variables described on the arterial and blood-pool FDG uptake. Tertile analyses revealed FDG circulation times of about 2.5 h and prescan glucose levels of less than 7.0 mmol/l, showing a favorable relationship between arterial and blood-pool FDG uptake. FDG circulation times showed negative associations with aortic meanSUVmax values as well as SVC and JV FDG blood-pool activity, but positive correlations with aortic and carotid meanTBRmax values. Prescan glucose levels were negatively associated with aortic and carotid meanTBRmax and carotid meanSUVmax values, but were positively correlated with SVC blood-pool uptake. The injected FDG dose failed to show any significant association with vascular FDG uptake. FDG circulation times and prescan blood glucose levels significantly affect FDG uptake in the aortic and carotid walls and may bias the results of image interpretation in patients undergoing vascular FDG PET/CT. The injected FDG dose was less critical. Therefore, circulation times of about 2.5 h and prescan glucose levels less than 7.0 mmol/l should be preferred in this setting.

Journal ArticleDOI
TL;DR: In patients with head and neck tumours, PET/MR showed equivalent performance to PET/CT in terms of qualitative results, and comparison of SUVs revealed an excellent correlation for measurements on both modalities, but underestimation ofSUVs measured on PET/ MR as compared to PET-CT.
Abstract: Purpose Our objectives were to assess the quality of PET images and coregistered anatomic images obtained with PET/MR, to evaluate the detection of focal uptake and SUV, and to compare these findings with those of PET/CT in patients with head and neck tumours.

Journal ArticleDOI
TL;DR: Lu-PRRT was shown to be an effective therapeutic option in patients with advanced progressive GI-NETs, showing an 84 % DCR that lasted for 25 months and a PFS of 36 months, and none of the patients, including those at a higher risk of toxicity, showed side-effects after either dosage of Lu- PRRT.
Abstract: We evaluated the activity and safety profile of 177Lu-Dotatate peptide receptor radionuclide therapy (Lu-PRRT) in patients with advanced, well-differentiated (G1-G2) gastrointestinal neuroendocrine tumors (GI-NETs). Forty-three patients with radiological tumor progression at baseline and a positive Octreoscan® completed the treatment with Lu-PRRT, resulting in the cumulative activity of 18.5 or 27.8 GBq in five cycles. Total activity was scheduled on the basis of kidney function or bone marrow reserve. Twenty-five (58 %) patients were treated with a “standard” Lu-PRRT full dosage (FD) of 25.7 GBq (range 22.2-27.8), while the remaining 18 patients (42 %) who, at enrolment, showed a higher probability of developing kidney or bone marrow toxicity received a reduced dosage (RD) of 18.4 GBq (range 14.4-20.4). According to SWOG criteria, the overall response was complete response (CR) in (7 %) cases and stable disease (SD) in 33 (77 %), with a disease control rate (DCR) of 84 %. Median response duration was 25 months (range 7-50). Median progression-free survival (PFS) was 36 months (95 % CI 24-nr), and median overall survival (OS) has not yet been reached. Remarkably, none of the patients, including those at a higher risk of toxicity, showed side-effects after either dosage of Lu-PRRT. Lu-PRRT was shown to be an effective therapeutic option in our patients with advanced progressive GI-NETs, showing an 84 % DCR (95 % CI 73-95) that lasted for 25 months and a PFS of 36 months. Both activities of 27.8 GBq and 18.5 GBq proved safe and effective in all patients, including those with a higher probability of developing kidney or bone marrow toxicity.

Journal ArticleDOI
TL;DR: Lung absorbed doses are significantly overestimated by pretreatment diagnostic 99mTc-MAA imaging, and Pretreatment diagnostic 166Ho-microsphere SPECT/CT imaging accurately predicts lung absorbed doses after 166Ho radioembolization.
Abstract: Radiation pneumonitis is a rare but serious complication of radioembolic therapy of liver tumours. Estimation of the mean absorbed dose to the lungs based on pretreatment diagnostic 99mTc-macroaggregated albumin (99mTc-MAA) imaging should prevent this, with administered activities adjusted accordingly. The accuracy of 99mTc-MAA-based lung absorbed dose estimates was evaluated and compared to absorbed dose estimates based on pretreatment diagnostic 166Ho-microsphere imaging and to the actual lung absorbed doses after 166Ho radioembolization. This prospective clinical study included 14 patients with chemorefractory, unresectable liver metastases treated with 166Ho radioembolization. 99mTc-MAA-based and 166Ho-microsphere-based estimation of lung absorbed doses was performed on pretreatment diagnostic planar scintigraphic and SPECT/CT images. The clinical analysis was preceded by an anthropomorphic torso phantom study with simulated lung shunt fractions of 0 to 30 % to determine the accuracy of the image-based lung absorbed dose estimates after 166Ho radioembolization. In the phantom study, 166Ho SPECT/CT-based lung absorbed dose estimates were more accurate (absolute error range 0.1 to −4.4 Gy) than 166Ho planar scintigraphy-based lung absorbed dose estimates (absolute error range 9.5 to 12.1 Gy). Clinically, the actual median lung absorbed dose was 0.02 Gy (range 0.0 to 0.7 Gy) based on posttreatment 166Ho-microsphere SPECT/CT imaging. Lung absorbed doses estimated on the basis of pretreatment diagnostic 166Ho-microsphere SPECT/CT imaging (median 0.02 Gy, range 0.0 to 0.4 Gy) were significantly better predictors of the actual lung absorbed doses than doses estimated on the basis of 166Ho-microsphere planar scintigraphy (median 10.4 Gy, range 4.0 to 17.3 Gy; p < 0.001), 99mTc-MAA SPECT/CT imaging (median 2.5 Gy, range 1.2 to 12.3 Gy; p < 0.001), and 99mTc-MAA planar scintigraphy (median 5.5 Gy, range 2.3 to 18.2 Gy; p < 0.001). In clinical practice, lung absorbed doses are significantly overestimated by pretreatment diagnostic 99mTc-MAA imaging. Pretreatment diagnostic 166Ho-microsphere SPECT/CT imaging accurately predicts lung absorbed doses after 166Ho radioembolization.

Journal ArticleDOI
TL;DR: 18 F-FAZA-PET could be used to identify and quantify tumor hypoxia before and during concomitant radio-chemotherapy in patients with locally advanced HNSCC and allowed the delineation of hypoxic volumes for dose escalation protocols.
Abstract: Hypoxia in head and neck squamous cell carcinoma (HNSCC) is associated with poor prognosis and outcome. 18 F-Fluoroazomycin arabinoside (FAZA) is a positron emission tomography (PET) tracer developed to enable identification of hypoxic regions within tumor. The aim of this study was to evaluate the use of 18 F-FAZA-PET for assessment of hypoxia before and during radiation therapy. Twelve patients with locally advanced HNSCC underwent 18 F-FAZA-PET scans before and at fraction 7 and 17 of concomitant chemo-radiotherapy. A hypoxic voxel was defined as a voxel expressing a standardized uptake value (SUV) equal or above the SUVmean of the posterior contralateral neck muscles plus three standard deviations. The fractional hypoxic volume fraction (FHV) and the spatial move of hypoxic volumes during treatment were analyzed. A hypoxic volume could be identified in ten patients before treatment. FAZA-PET FHV varied from 0 to 54.3 % and from 0 to 41.4 % in the primary tumor and in the involved node, respectively. Six out of these ten patients completed all the FAZA-PET-computed tomography (CT) during the radiotherapy. In all patients, FHV and SUVmax values decreased. All patient presented a spatial move of hypoxic volume, but only three patients had newborn hypoxic voxels after 17 fractions. This study indicated that 18 F-FAZA-PET could be used to identify and quantify tumor hypoxia before and during concomitant radio-chemotherapy in patients with locally advanced HNSCC. In addition to the information on prognostic value, the use of 18 F-FAZA-PET allowed the delineation of hypoxic volumes for dose escalation protocols. However, due to fluctuation of hypoxia during treatment, repeated scan will have to be performed (i.e. adaptive radiotherapy).

Journal ArticleDOI
TL;DR: Increased 18F-florbetapir binding values were found in patients with late-life major depression relative to comparison subjects in specific brain regions, despite no differences in age, sex, education, Mini Mental Status Examination score, vascular risk factor score, homocysteine and ApoE ε4 genotype between the two groups.
Abstract: Purpose The literature suggests that a history of depression is associated with an increased risk of developing Alzheimer’s disease (AD). The aim of this study was to examine brain amyloid accumulation in patients with lifetime major depression using 18F-florbetapir (AV-45/Amyvid) PET imaging in comparison with that in nondepressed subjects.

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TL;DR: ALS patients with the C9ORF72 hexanucleotide repeat expansion had a more widespread central nervous system involvement than ALS patients without genetic mutations, with or without comorbid FTD, consistent with their more severe clinical picture.
Abstract: Purpose Recently, a GGGGCC hexanucleotide repeat expansion in the C9ORF72 gene, located on chromosome 9p21 has been demonstrated to be the commonest cause of familial amyotrophic lateral sclerosis (ALS) and to account for 5 to 10 % of apparently sporadic ALS. Relatively little is known about the brain metabolism profile of patients carrying the expansion. Our aim was to identify the [18F]FDG PET profile in ALS patients with the C9ORF72 expansion (C9ORF72-ALS).

Journal ArticleDOI
TL;DR: 11C-choline PET/CT had a significant impact on therapeutic management in rPCa patients, with a major clinical change implemented in 46.7 % of patients, and the effect of such treatment changes on patient survival is needed.
Abstract: Purpose The aim of this retrospective two-centre study was to investigate the clinical impact of 11C-choline PET/CT on treatment management decisions in patients with recurrent prostate cancer (rPCa) after radical therapy.