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1.
J Nucl Med ; 2019 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-31519804

RESUMO

Treatment of patients with advanced medullary thyroid carcinoma (MTC) is still a challenge. For more than 2 decades it is known that cholecystokinine-2 receptor (CCK2R) is a promising target for the treatment of MTC with radiolabeled minigastrin analogues. Unfortunately, kidney toxicity precluded their therapeutic application so far. In 6 consecutive patients we evaluated with advanced 3D dosimetry whether improved minigastrin analogue 177Lu-DOTA-(DGlu)6-Ala-Tyr-Gly-Trp-Nle-Asp-PheNH2 (177Lu-PP-F11N) is a suitable agent for the treatment of MTC. Methods: Patients received two injections of about 1 GBq (~80 µg) 177Lu-PP-F11N with and without a solution of succinylated gelatin (SG, a plasma expander used for nephroprotection) in a random cross-over sequence in order to evaluate biodistribution, pharmacokinetics as well as tumor- and organ dosimetry. ECG, blood count and blood chemistry were measured up to 12 weeks after administration of 177Lu-PP-F11N to assess safety. Results: In all patients 177Lu-PP-F11N accumulation was visible in tumor tissue, stomach and kidneys. Altogether 13 tumors were eligible for dosimetry. The median (interquartile range = IQR) absorbed dose for tumors, stomach, kidneys and bone marrow was 0.88 Gy/GBq (0.85-1.04), 0.42 (0.25-1.01), 0.11 (0.07-0.13) and 0.028 (0.026-0.034). These resulted in a median (IQR) tumor-to-kidney dose ratio of 11.6 (8.11-14.4) without SG and 13.0 (10.2-18.6) with SG, which were not significantly different (P = 1.0). The median (IQR) tumor-to-stomach dose ratio was 3.34 (1.14-4.7). Adverse reactions (mainly hypotension, flushing and hypokalemia) were self-limiting and not higher than grade 1. Conclusion: 177Lu-PP-F11N accumulates specifically in MTC at a dose that is sufficient for a therapeutic approach. With little kidney and bone marrow radiation dose 177Lu-PP-F11N shows promising biodistribution. The dose limiting organ is most likely the stomach. Further clinical studies are necessary to evaluate the maximum tolerated dose and the efficacy of 177Lu-PP-F11N.

2.
J Nucl Cardiol ; 2019 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-31538322

RESUMO

PURPOSE: While a visual interpretation of 99mTc-DPD scintigraphy by means of Perugini score can provide a reliable diagnosis of transthyretin-related (ATTR) cardiac amyloidosis (CA), a quantitative approach is expected to play a major role in risk stratification and therapy evaluation. The aim of our study was to test the feasibility of a quantitative assessment and to correlate various parameters to Perugini score. METHODS: in this retrospective study, consecutive patients underwent a 99mTc-DPD whole-body bone scintigraphy and a SPECT/CT of the thorax. XSPECT-QUANT software was used to quantify the DPD uptake in the heart. RESULTS: Thirteen patients were included. CA was confirmed in 8 and rejected in 5. Myocardial SUVmax and SUVpeak showed a fairly strong correlation with Perugini score (both ρ = .71, P = .006). Same held true for to-bone normalized values (both ρ = .75, P = .003). There was a great degree of overlap for quantitative values in patients with Perugini score 2 and 3. CONCLUSION: Quantitative 99mTc-DPD SPECT/CT in suspected ATTR CA patients is feasible and allows for a more accurate assessment of myocardial uptake.

3.
J Clin Endocrinol Metab ; 104(12): 5843-5852, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31298706

RESUMO

CONTEXT: Surgical intervention is advised in patients with multiple endocrine neoplasia type-1 (MEN-1) and nonfunctioning pancreatic neuroendocrine tumors (PanNETs) with a size ≥20 mm. Functioning PanNETs, such as in patients with endogenous hyperinsulinemic hypoglycemia (EHH) due to (one or multiple) insulinomas, should be treated surgically independent of size. Preoperative localization of insulinomas is critical for surgery. OBJECTIVE: To evaluate the feasibility and sensitivity of 68Ga-DOTA-exendin-4 positron emission tomography (PET)/CT in the detection of clinically relevant lesions in patients with MEN-1 and EHH in combination with MRI. DESIGN: Post hoc subgroup analysis of a larger prospective imaging study with 52 patients with EHH. PATIENTS: Six of 52 consecutive patients with EHH and genetically proven MEN-1 mutation were included. INTERVENTIONS: All patients received one 68Ga-DOTA-exendin-4 PET/CT and one MRI scan within 3 to 4 days. Thereafter, surgery was performed based on all imaging results. MAIN OUTCOME MEASURES: Lesion-based sensitivity of PET/CT and MRI for detection of clinically relevant lesions was calculated. Readers were unaware of other results. The reference standard was surgery with histology and treatment outcome. True positive (i.e., clinically relevant lesions) was defined as PanNETs ≥20 mm or insulinoma. RESULTS: In six patients, 37 PanNETs were confirmed by histopathology. Sensitivity (95% CI) in the detection of clinically relevant lesions for combined PET/CT plus MRI, MRI, and PET/CT was 92.3% (64% to 99.8%), 38.5% (13.9% to 68.4%), and 84.6% (54.6% to 98.1%), respectively (P = 0.014 for the comparison of PET/CT plus MRI vs MRI). Postsurgery, EHH resolved in all patients. CONCLUSION: 68Ga-DOTA-exendin-4 PET/CT is feasible in patients with MEN-1 and EHH. The combination with MRI is superior to MRI alone in the detection of insulinomas and may guide the surgical strategy.

5.
Eur Heart J Acute Cardiovasc Care ; : 2048872619842988, 2019 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-31008655

RESUMO

AIM: Exercise stress testing is used to detect myocardial ischaemia, but is limited by low sensitivity and specificity. The authors investigated the value of the analysis of high-frequency QRS components as a marker of abnormal depolarization in addition to standard ST-deviations as a marker of abnormal repolarization to improve the diagnostic accuracy. METHODS AND RESULTS: Consecutive patients undergoing bicycle exercise stress nuclear myocardial perfusion imaging were prospectively enrolled. Presence of myocardial ischaemia, the primary diagnostic endpoint, was adjudicated using MPI and coronary angiography. Automated high-frequency QRS analysis was performed in a blinded fashion. The prognostic endpoint was major adverse cardiac events (MACEs) during two years of follow-up. Exercise-induced ischaemia was detected in 147/662 patients (22%). The sensitivity of high-frequency QRS was similar to ST-deviations (46% vs. 43%, p=0.59), while the specificity was lower (75% vs. 87%, p<0.001). The combined use of high-frequency QRS and ST-deviations classified 59% of patients as 'rule-out' (both negative), 9% as 'rule-in' (both positive) and 32% in an intermediate zone (one test positive). The sensitivity for 'rule-out' and the specificity for 'rule-in' improved to 63% and 97% compared with ST-deviation analysis alone (both p<0.001). MACE-free survival was 90%, 80% and 42% in patients in the 'rule-out', intermediate and 'rule-in' groups ( p<0.001). After adjustment for age, gender, ST-deviations and clinical post-test probability of ischaemia, high-frequency QRS remained an independent predictor for the occurrence of MACEs. CONCLUSION: The use of high-frequency QRS analysis in addition to ST-deviation analysis improves the diagnostic accuracy during exercise stress testing and adds independent prognostic information.

6.
Swiss Med Wkly ; 149: w20017, 2019 02 25.
Artigo em Inglês | MEDLINE | ID: mdl-30852831

RESUMO

Molecular imaging has found numerous applications in oncology as many tumours express or activate tumour specific target molecules or pathways. This relatively new imaging technique results in a better localisation of tumours and improved tumour staging, especially in the setting of hybrid imaging that is in combination with morphological imaging such as computed tomography. In well differentiated neuroendocrine tumours, somatostatin receptor imaging, as one of the first examples of receptor targeted imaging in humans, plays an important role in the diagnostic work-up of these patients. In poorly differentiated neuroendocrine tumours or medullary thyroid carcinoma, 18F-fluorodeoxyglucose PET/CT and dihydroxyphenylalanine PET/CT play an important role due to the limitations of the somatostatin receptor imaging in these tumour entities. These limitations prompted the development of innovations such as radiolabelled somatostatin receptor antagonists for imaging all types of NET and glucagon-like peptide-1 receptor agonists for the imaging of insulinomas. The current review summarises the actual state of knowledge in the field.


Assuntos
Carcinoma Neuroendócrino/diagnóstico por imagem , Receptor do Peptídeo Semelhante ao Glucagon 1 , Imagem Molecular/métodos , Tumores Neuroendócrinos/diagnóstico por imagem , Receptores de Somatostatina , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Fluordesoxiglucose F18 , Humanos , Estadiamento de Neoplasias/métodos , Tumores Neuroendócrinos/patologia , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos/administração & dosagem , Receptores de Somatostatina/metabolismo , Tomografia Computadorizada por Raios X
7.
Clin Nucl Med ; 44(5): e347-e348, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30889001

RESUMO

Insulinomas are often difficult to localize. We present a 47-year-old woman who had recurrent neuroglycopenic symptoms and positive Whipple triad for 28 months. The 14 hours of fasting test confirmed the diagnosis of endogenous hyperinsulinemic hypoglycemia which is highly suspicious for the presence of an insulinoma. Previously performed MRI, endoscopic ultrasound, In-pentetreotide SPECT/CT, and Ga-DOTA-exendin-4 PET/CT did not show any evidence of an insulinoma. Subsequently, Ga-DOTA-exendin-4 PET/CT was repeated with the previous infusion of a colloidal volume replacement fluid (Gelofusine), known to reduce Ga-DOTA-exendin-4 accumulation in the kidneys. Consequently, the insulinoma was unmasked from the left kidney, allowing curative surgery.


Assuntos
Insulinoma/diagnóstico por imagem , Neoplasias Pancreáticas/diagnóstico por imagem , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Feminino , Humanos , Pessoa de Meia-Idade , Compostos Organometálicos , Peptídeos , Compostos Radiofarmacêuticos
8.
Eur J Clin Invest ; : e13112, 2019 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-30925205

RESUMO

BACKGROUND: The phenomenon of exercise-induced left ventricular dysfunction (LVD) is incompletely understood. Better understanding of its prevalence and determinants might help to address the current potential oversimplification of the relation between physical activity and cardiac health in patients with coronary artery disease (CAD). METHODS: We prospectively assessed the prevalence and determinants of exercise-induced LVD in patients with stable CAD and normal LV function at rest undergoing bicycle rest/stress myocardial perfusion imaging single-photon emission computed tomography (MPI-SPECT). Exercise-induced LVD was defined as a relevant (5% or more) drop in left ventricular ejection fraction after maximal exercise. High-sensitivity cardiac troponin I/T (Hs-cTnI/T) and N-terminal probrain natriuretic peptide (NT-proBNP) concentrations were measured before exercise to quantify cardiomyocyte injury and hemodynamic cardiac stress, respectively. RESULTS: Among 317 patients, exercise-induced LVD was present in 83 (26%) patients. Exercise-induced LVD was associated with the extent of exercise-inducible myocardial ischaemia as well as transient ischaemic dilatation. Still, 43% of patients developing exercise-induced LVD did not have functionally relevant CAD. Neither baseline characteristics, nor the quantification of the extent of cardiomyocyte injury and hemodynamic cardiac stress using hs-cTnI/T and NT-proBNP concentrations, respectively, allowed predicting exercise-induced LVD. CONCLUSION: One out of four patients with stable CAD develops exercise-induced LVD after bicycle exercise test. While the extent of exercise-inducible myocardial ischaemia is a predictor, other still unrecognized mechanisms also seem to play a major role, as nearly half of all patients with exercise-induced LVD do not have functionally relevant CAD.

9.
Contrast Media Mol Imaging ; 2019: 6438196, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30733648

RESUMO

Introduction: 177Lu-OPS201 is a high-affinity somatostatin receptor subtype 2 antagonist for PRRT in patients with neuroendocrine tumors. The aim is to find the optimal scaling for dosimetry and to compare the biokinetics of 177Lu-OPS201 in animals and humans. Methods: Data on biokinetics of 177Lu-OPS201 were analyzed in athymic nude Foxn1 nu mice (28 F, weight: 26 ± 1 g), Danish Landrace pigs (3 F-1 M, weight: 28 ± 2 kg), and patients (3 F-1 M, weight: 61 ± 17 kg) with administered activities of 0.19-0.27 MBq (mice), 97-113 MBq (pigs), and 850-1086 MBq (patients). After euthanizing mice (up to 168 h), the organ-specific activity contents (including blood) were measured. Multiple planar and SPECT/CT scans were performed until 250 h (pigs) and 72 h (patients) to quantify the uptake in the kidneys and liver. Blood samples were taken up to 23 h (patients) and 300 h (pigs). In pigs and patients, kidney protection was applied. Time-dependent uptake data sets were created for each species and organ/tissue. Biexponential fits were applied to compare the biokinetics in the kidneys, liver, and blood of each species. The time-integrated activity coefficients (TIACs) were calculated by using NUKFIT. To determine the optimal scaling, several methods (relative mass scaling, time scaling, combined mass and time scaling, and allometric scaling) were compared. Results: A fast blood clearance of the compound was observed in the first phase (<56 h) for all species. In comparison with patients, pigs showed higher liver retention. Based on the direct comparison of the TIACs, an underestimation in mice (liver and kidneys) and an overestimation in pigs' kidneys compared to the patient data (kidney TIAC: mice = 1.4 h, pigs = 7.7 h, and patients = 5.8 h; liver TIAC: mice = 0.7 h, pigs = 4.1 h, and patients = 5.3 h) were observed. Most similar TIACs were obtained by applying time scaling (mice) and combined scaling (pigs) (kidney TIAC: mice = 3.9 h, pigs = 4.8 h, and patients = 5.8 h; liver TIAC: mice = 0.9 h, pigs = 4.7 h, and patients = 5.3 h). Conclusion: If the organ mass ratios between the species are high, the combined mass and time scaling method is optimal to minimize the interspecies differences. The analysis of the fit functions and the TIACs shows that pigs are better mimicking human biokinetics.


Assuntos
Dosimetria in Vivo/métodos , Lutécio/análise , Compostos Organometálicos/farmacocinética , Radioisótopos/análise , Animais , Feminino , Humanos , Rim/metabolismo , Fígado/metabolismo , Masculino , Camundongos , Compostos Organometálicos/química , Receptores de Somatostatina/antagonistas & inibidores , Suínos
10.
J Nucl Med ; 2018 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-30504139

RESUMO

Being highly expressed in insulinomas, the glucagon-like peptide-1 receptor (GLP-1R) is a potential target for diagnosis, localization and treatment with the radiolabeled GLP-1R agonist exendin. Tracer accumulation in the kidneys, however, hampers accurate diagnostic visualization of pancreatic tissue and prohibits the therapeutic application of radiolabeled exendin for beta-cell-derived tumors. Therefore, we evaluated the ability of succinylated gelatin (Gelofusine) to reduce the renal accumulation of radiolabeled exendin in humans and we performed dosimetric calculations to estimate the maximum absorbed insulinoma dose that could be achieved when exendin would be used for peptide receptor radionuclide therapy. Methods: Ten healthy volunteers received 50 MBq 111In-exendin-4, in combination with Gelofusine or saline in a crossover design. SPECT/CT images were obtained after 24 hours. The procedure was repeated three weeks later. Uptake of 111In-exendin was determined by drawing regions of interest around the kidneys and in the pancreas. Planar scintigraphic 111In-exendin images of five insulinoma patients were used for dosimetry studies estimating the maximum insulinoma absorbed dose that could be achieved without causing radiotoxicity to other organs. Results: Gelofusine reduced the renal accumulation of 111In-exendin-4 with 18.1%, whereas the pancreatic uptake remained unchanged. In 3 out of 10 subjects, the kidney uptake was reduced to such an extent that the pancreatic tail could be better discriminated from the kidney signal. Dosimetric estimations suggested that the insulinoma absorbed dose ranges from 30.3-127.8 Gy. This dose could be further increased to maximally 156.1 Gy when Gelofusine would be used. Conclusion: We have shown that Gelofusine can reduce the renal accumulation of 111In-exendin-4 in humans. This reduction does not only allow more accurate qualitative and quantitative analyses of radiolabeled exendin uptake in the tail region of the pancreas, but it also potentiates the safe delivery of a higher radiation dose to GLP-1R positive tumors for therapy.

11.
Swiss Med Wkly ; 148: w14682, 2018 11 05.
Artigo em Inglês | MEDLINE | ID: mdl-30449018

RESUMO

BACKGROUND Important causes of endogenous hyperinsulinaemic hypoglycaemia (EHH) in adult patients are insulinoma and adult nesidioblastosis. Data on main symptoms in EHH are scarce and controversial. We analysed main symptoms of patients with EHH in the framework of two prospective studies investigating glucagon-like peptide-1 receptor imaging. METHODS Patients were referred from secondary European endocrine centres and endocrinologists. Inclusion criteria were biochemically proven EHH (glucose <2.5 mmol/l in the presence of inadequate insulin and C-peptide levels) with neurological hypoglycaemic symptoms. Demographic characteristics and aetiologies of the patients with EHH were retrieved. Main symptoms were categorised into neurological, sympathicoadrenal (sweating, tremor, palpitation, hunger, shivering and pallor) and nonspecific other symptoms (nonspecific asthenia, weight gain, gastrointestinal symptoms and headaches). Neurological symptoms were subdivided into moderately impaired consciousness (confusion, dizziness, somnolence and delirium), visual, speech and sensorimotor impairment, severely impaired consciousness (loss of consciousness and apathy), attention deficit, seizures and personality changes. Biochemical assessment and duration of EHH at the end of a fasting test were recorded. RESULTS Fifty-four patients with full documentation were included in the analysis (74% female; mean age 54 years, range 22­84). Median duration from onset of symptoms to diagnosis of EHH was 12 months (range 0­120). Fifty (92.6%) patients had neurological symptoms, including moderately impaired consciousness (46.3%), visual, speech and sensorimotor function impairment (44.4%), severely impaired consciousness (37%), attention deficit (31.5%), seizures (16.7%) and personality change (13%). Sympathicoadrenal symptoms were present in 33 (61.1%) patients. Nonspecific other symptoms occurred in 36 (66.7%) patients. 43 patients (79.6%) suffered from symptoms of at least two different categories. CONCLUSIONS Clinical symptoms of EHH are characterised by a wide variety of mainly different neurological symptoms ("neurological chameleon"). EHH should be considered as a differential diagnosis in many neurological disorders. Trial registration numbers NCT00937079 & NCT02127541

13.
Clin Chem ; 64(11): 1596-1606, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30097496

RESUMO

BACKGROUND: We aimed to directly compare high-sensitivity cardiac troponin I (hs-cTnI) and high-sensitivity cardiac troponin T (hs-cTnT) in the detection of functionally relevant coronary artery disease (fCAD). METHODS: Consecutive patients referred with clinical suspicion of fCAD and no structural heart disease other than coronary artery disease were included. The presence of fCAD was based on rest/stress myocardial perfusion single-photon emission computed tomography/computed tomography and coronary angiography. hs-cTnI and hs-cTnT concentrations were measured in a blinded fashion. Diagnostic accuracy was quantified using the area under the ROC curve (AUC) and evaluated both for uniform use in all patients and for sex-specific use in women and men separately. The prognostic end point was major adverse cardiac events (MACEs; cardiovascular death or myocardial infarction) within 2 years. For the prognostic performance, we used a multivariable model comparison with the Akaike information criterion (AIC). RESULTS: fCAD was detected in 613 of 2062 patients (29.7%) overall, 112 of 664 of women (16.9%), and 501 of 1398 of men (35.8%). hs-cTnI and hs-cTnT had comparable diagnostic accuracy when assessed for uniform use in all patients (AUC, 0.68 vs 0.66; P = 0.107) and separately in women (AUC, 0.68 vs 0.63; P = 0.068) and men (AUC, 0.65 vs 0.64; P = 0.475). However, women required lower rule-out cutoffs to achieve high sensitivity, and men needed higher rule-in cutoffs to achieve high specificity. hs-cTnI and hs-cTnT were strongly and independently associated with MACE within 2 years (P < 0.001), with comparable prognostic accuracies by the AIC. CONCLUSIONS: hs-cTnI and hs-cTnT provide moderate and comparable diagnostic accuracy. Sex-specific cutoffs may be preferred. The prognostic utility of both troponins is comparable.

14.
J Nucl Med ; 2018 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-30002107

RESUMO

Patients with metastatic medullary thyroid cancer (MTC) have limited systemic treatment options. The use of radiolabeled gastrin analogs targeting the cholecystokinin-2 receptor (CCK2R) is an attractive approach. However, their therapeutic efficacy is presumably decreased by their enzymatic degradation in vivo. We aimed to investigate whether the chemically stabilized analog 177Lu-DOTA-PP-F11N (177Lu-DOTA-(DGlu)6-Ala-Tyr-Gly-Trp-Nle-Asp-Phe-NH2) performs better than reference analogs with varying in vivo stability, namely 177Lu-DOTA-MG11 (177Lu-DOTA-DGlu-Ala-Tyr-Gly-Trp-Met-Asp-Phe-NH2) and 177Lu-DOTA-PP-F11 (177Lu-DOTA-(DGlu)6-Ala-Tyr-Gly-Trp-Met-Asp-Phe-NH2), and if the use of protease inhibitors further improves CCKR2-targeting. First human data on 177Lu-DOTA-PP-F11N are also reported. Methods: In vitro stability of all analogs was assessed against a panel of extra- and intra-cellular endoproteases, while their in vitro evaluation was performed using the human MTC MZ-CRC-1 and the transfected A431-CCK2R(+) cell lines. Biodistribution without and with the protease inhibitors phosphoramidon (PA) and thiorphan (TO) was assessed 4h post-injection in MZ-CRC-1 and A431-CCK2R(+) dual xenografts. Autoradiography of 177Lu-DOTA-PP-F11N (without and with PA) and nanoSPECT/CT images were performed. SPECT/CT images of 177Lu-DOTA-PP-F11N in a metastatic MTC patient were also acquired. Results: natLu-DOTA-PP-F11N is less of a substrate for neprilysines than the other analogs, while intracellular cysteine proteases, like cathepsins-L, might be involved in the degradation of gastrin analogs. The uptake of all radiotracers was higher in MZ-CRC-1 tumors, compared to A431-CCK2R(+), apparently due to the higher number of binding sites on MZ-CRC-1 cells. 177Lu-DOTA-PP-F11N has the same biodistribution as 177Lu-DOTA-PP-F11, however, the uptake in the MZ-CRC-1 tumors is almost double (20.7±1.71 vs 11.2±2.94 %IA/g, P = 0.0002). Co-administration of PA or TO increases significantly the 177Lu-DOTA-MG11 uptake in the CCK2R(+) tumors and stomach. Less profound is the effect on 177Lu-DOTA-PP-F11, while no influence or even reduction is observed for 177Lu-DOTA-PP-F11N (20.7±1.71 vs 15.6±3.80 (with PA) %IA/g, p<0.05 in MZ-CRC-1 tumors). First clinical data show high 177Lu-DOTA-PP-F11N accumulation in the tumors, stomach, kidneys and colon. Conclusion: The performance of 177Lu-DOTA-PP-F11N without protease inhibitors is as good as the performance of 177Lu-DOTA-MG11 in the presence of inhibitors. The human application of single compounds without unessential additives is preferable. Preliminary clinical data spotlight stomach as a potential dose-limiting organ beside the kidneys.

15.
Eur J Nucl Med Mol Imaging ; 45(13): 2318-2327, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30054698

RESUMO

PURPOSE: Benign insulinomas are the most prevalent cause of endogenous hyperinsulinaemic hypoglycaemia (EHH) in adults, and because of their small size are difficult to localise. The purpose of the study was to test the diagnostic accuracy and clinical impact of glucagon-like peptide-1 receptor (GLP-1R) PET/CT using 68Ga-DOTA-exendin-4 in consecutive adult patients referred for localisation of insulinomas. The results were compared with 111In-DOTA-exendin-4 SPECT/CT, study-MRI and previously performed external CT and/or MRI (prior external CT/MRI). METHODS: We prospectively enrolled patients with neuroglycopenic symptoms due to EHH. GLP-1R PET/CT, SPECT/CT and study-MRI were performed in a randomised, crossover order within 3-4 days. The reference standard was surgery with histology and treatment outcome. RESULTS: From January 2014 until March 2017, 52 patients were recruited. All imaging and invasive procedures before recruitment identified suspicious lesions in 46.2% of patients. GLP-1R PET/CT, SPECT/CT and study-MRI detected suspicious lesions in 78.8%, 63.5% and 63.4% of patients, respectively. In 38 patients, conclusive histology was available for final analysis. Accuracy (95% confidence interval) for PET/CT, SPECT/CT, study-MRI and prior external CT/MRI was 93.9% (87.8-97.5%), 67.5% (58.1-76.0%), 67.6% (58.0-76.1%) and 40.0% (23.9-57.9%), respectively (all P values < 0.01, except comparison of SPECT/CT and study-MRI with a P value = 1.0). Impact on clinical management was 42.3%, 32.7% and 33.3% for PET/CT, SPECT/CT and study-MRI, respectively. Percentage reading agreement was 89.5%, 75.7%, and 71.1% for PET/CT, SPECT/CT and study-MRI, respectively. CONCLUSION: 68Ga-DOTA-exendin-4 PET/CT performed significantly better than 111In-DOTA-exendin-4 SPECT/CT and MRI in the localisation of benign insulinomas and should be considered in patients where localisation fails with CT/MRI ( ClinicalTrials.gov , NCT02127541).

16.
Clin Res Cardiol ; 107(9): 824-835, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29667014

RESUMO

BACKGROUND: Myocardial scar is associated with adverse cardiac outcomes. The Selvester QRS-score was developed to estimate myocardial scar from the 12-lead ECG, but its manual calculation is difficult. An automatically computed QRS-score would allow identification of patients with myocardial scar and an increased risk of mortality. OBJECTIVES: To assess the diagnostic and prognostic value of the automatically computed QRS-score. METHODS: The diagnostic value of the QRS-score computed automatically from a standard digital 12-lead was prospectively assessed in 2742 patients with suspected myocardial ischemia referred for myocardial perfusion imaging (MPI). The prognostic value of the QRS-score was then prospectively tested in 1151 consecutive patients presenting to the emergency department (ED) with suspected acute heart failure (AHF). RESULTS: Overall, the QRS-score was significantly higher in patients with more extensive myocardial scar: the median QRS-score was 3 (IQR 2-5), 4 (IQR 2-6), and 7 (IQR 4-10) for patients with 0, 5-20 and > 20% myocardial scar as quantified by MPI (p < 0.001 for all pairwise comparisons). A QRS-score ≥ 9 (n = 284, 10%) predicted a large scar defined as > 20% of the LV with a specificity of 91% (95% CI 90-92%). Regarding clinical outcomes in patients presenting to the ED with symptoms suggestive of AHF, mortality after 1 year was 28% in patients with a QRS-score ≥ 3 as opposed to 20% in patients with a QRS-score < 3 (p = 0.001). CONCLUSIONS: The QRS-score can be computed automatically from the 12-lead ECG for simple, non-invasive and inexpensive detection and quantification of myocardial scar and for the prediction of mortality. TRIAL-REGISTRATION: http://www.clinicaltrials.gov . Identifier, NCT01838148 and NCT01831115.


Assuntos
Algoritmos , Cicatriz/patologia , Eletrocardiografia/métodos , Processamento Eletrônico de Dados/métodos , Isquemia Miocárdica/mortalidade , Miocárdio/patologia , Idoso , Cicatriz/etiologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/complicações , Isquemia Miocárdica/diagnóstico , Tomografia por Emissão de Pósitrons , Estudos Prospectivos , Reprodutibilidade dos Testes , Fatores de Risco , Taxa de Sobrevida/tendências , Suíça/epidemiologia
18.
Clin Biochem ; 52: 33-40, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29107010

RESUMO

BACKGROUND: Single biomarker approaches provide only moderate accuracy in the non-invasive detection of exercise-induced myocardial ischemia. We therefore assessed the combination of the two most promising single biomarkers: high-sensitivity cardiac troponin I (hs-cTnI) and B-type natriuretic peptide (BNP). METHODS: Consecutive patients with suspected myocardial ischemia referred to stress myocardial perfusion single-photon emission tomography imaging (MPI) were enrolled. Clinical judgment (CJ) of the treating cardiologist regarding myocardial ischemia, quantified using a visual analogue scale, and blood concentrations of hs-cTnI and BNP were determined before and after stress. The presence of myocardial ischemia was adjudicated by independent cardiologists using MPI, blinded to biomarker measurements. Death and acute myocardial infarction (AMI) during follow-up were the prognostic endpoints. RESULTS: Among 1142 consecutive patients inducible myocardial ischemia was found in 456 (40%) of all patients. For the detection of inducible myocardial ischemia, CJ before exercise stress testing (CJb) showed an area under the receiver-operating-characteristics curve (AUC) of 0.66 (95%CI 0.63-0.69), hs-cTnI 0.70 (95%CI 0.67-0.73, p=0.07 vs CJb), and BNP 0.66 (95%CI 0.62-0.69, p=0.98). The use of a dual-biomarker strategy combining hs-cTnI and BNP with CJb did not provide a significant advantage over the combination of hs-cTnI alone and CJb (AUC 0.74, 95%CI 0.72-0.77 vs AUC 0.74, 95%CI 0.71-0.77, p=0.16). Hs-cTnI showed good prognostic value for AMI (HR 1.6, 95%CI 1.3-1.9), and BNP for death (HR 1.6, 95%CI 1.3-2.1). CONCLUSION: A dual-biomarker strategy combing BNP and hs-cTnI does not further increase diagnostic accuracy on top of clinical judgment and hs-cTnI alone. SUMMARY AND HIGHLIGHTS: We included 1142 consecutive patients with suspected inducible ischemia, and evaluated the added value of the biomarkers high-sensitivity cardiac troponin (hs-cTn) and B-type natriuretic peptide (BNP), alone and in combination, on top of clinical judgment. CLINICAL TRIAL REGISTRATION: Biochemical and Electrocardiographic Signatures in the Detection of Exercise-induced Myocardial Ischemia (BASEL VIII), NCT01838148, https://clinicaltrials.gov/ct2/show/NCT01838148.


Assuntos
Isquemia Miocárdica/diagnóstico , Peptídeo Natriurético Encefálico/análise , Idoso , Área Sob a Curva , Biomarcadores/sangue , Doença da Artéria Coronariana/sangue , Eletrocardiografia , Exercício , Teste de Esforço/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/sangue , Isquemia Miocárdica/sangue , Peptídeo Natriurético Encefálico/sangue , Prognóstico , Curva ROC , Tomografia Computadorizada de Emissão de Fóton Único , Troponina I/análise , Troponina I/sangue
19.
J Nucl Med ; 59(6): 909-914, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29025985

RESUMO

Preclinical and preliminary clinical evidence indicates that radiolabeled somatostatin (sst) receptor antagonists perform better than agonists in detecting neuroendocrine tumors (NETs). We performed a prospective phase I/II study to evaluate the sst receptor antagonist 68Ga-OPS202 (68Ga-NODAGA-JR11; NODAGA = 1,4,7-triazacyclononane,1-glutaric acid-4,7-acetic acid and JR11 = Cpa-c(dCys-Aph(Hor)-dAph(Cbm)-Lys-Thr-Cys)-dTyr-NH2)) for PET imaging. Here, we report the results of phase I of the study. Methods: Patients received 2 single 150-MBq intravenous injections of 68Ga-OPS202 3-4 wk apart (15 µg of peptide at visit 1 and 50 µg at visit 2). At visit 1, a dynamic PET/CT scan over the kidney was obtained during the first 30 min after injection, and static whole-body scans were obtained at 0.5, 1, 2, and 4 h after injection; at visit 2, a static whole-body scan was obtained at 1 h. Blood samples and urine were collected at regular intervals to determine 68Ga-OPS202 pharmacokinetics. Safety, biodistribution, radiation dosimetry, and the most appropriate imaging time point for 68Ga-OPS202 were assessed. Results: Twelve patients with well-differentiated gastroenteropancreatic (GEP) NETs took part in the study. 68Ga-OPS202 cleared rapidly from the blood, with a mean residence time of 2.4 ± 1.1 min/L. The organs with the highest mean dose coefficients were the urinary bladder wall, kidneys, and spleen. The calculated effective dose was 2.4E-02 ± 0.2E-02 mSv/MBq, corresponding to 3.6 mSv, for a reference activity of 150 MBq. Based on total numbers of detected malignant lesions, the optimal time window for the scan was between 1 and 2 h. For malignant liver lesions, the time point at which most patients had the highest mean tumor contrast was 1 h. 68Ga-OPS202 was well tolerated; adverse events were grade 1 or 2, and there were no signals of concern from laboratory blood or urinalysis tests. Conclusion:68Ga-OPS202 showed favorable biodistribution and imaging properties, with optimal tumor contrast between 1 and 2 h after injection. Dosimetry analysis revealed that the dose delivered by 68Ga-OPS202 to organs is similar to that delivered by other 68Ga-labeled sst analogs. Further evaluation of 68Ga-OPS202 for PET/CT imaging of NETs is therefore warranted.

20.
Clin Chem ; 64(2): 386-395, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29038153

RESUMO

BACKGROUND: This study aimed to prospectively advance a rule-out strategy for functionally significant coronary artery disease (CAD) by use of high-sensitivity cardiac troponin I (hs-cTnI) from bench to bedside, by application of a 3-step approach: validation in serum, correlation in plasma, and application on a clinical platform. METHODS: Patients without known CAD referred for rest/stress myocardial perfusion single-photon emission tomography/computer tomography (MPI-SPECT/CT) were assigned to 3 consecutive cohorts: validation, correlation, and application. Functionally relevant CAD was adjudicated with the use of expert interpretation of MPI-SPECT/CT and, if available, coronary angiography. In the validation cohort resting hs-cTnI was measured in serum before stress testing with the research Erenna system, in serum and plasma in the correlation cohort with the research Erenna system, and in plasma in the application cohort with the clinical Clarity system. RESULTS: Overall, functionally relevant CAD was adjudicated in 21% (304/1478) of patients. In the validation cohort (n = 613), hs-cTnI concentrations were significantly higher in patients with functionally relevant CAD (median 2.8 ng/L vs 1.9 ng/L, P < 0.001) as compared to patients without functionally relevant CAD and allowed a rule out with 95% sensitivity in 14% of patients. In the correlation cohort (n = 606), hs-cTnI concentrations in serum and plasma strongly correlated (Spearman r = 0.921) and had similar diagnostic accuracy as quantified by the area under the receiver operating characteristic curve (0.686 vs 0.678, P = 0.425). In the application cohort (n = 555), very low hs-cTnI plasma concentrations (< 0.5 ng/L) ruled out functionally relevant CAD with 95% sensitivity in 10% of patients. CONCLUSIONS: A single resting plasma hs-cTnI measurement can safely rule out functionally relevant CAD in around 10% of patients without known CAD.

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