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BACKGROUND: Lymph node metastasis is an important prognostic factor in locally advanced cervical cancer (LACC). No imaging method can successfully detect all (micro)metastases. This may result in (lymph node) recurrence after chemoradiation. We hypothesized that lymphatic mapping could identify nodes at risk and if radiation treatment volumes are adapted based on the lymphatic map, (micro)metastases not shown on imaging could be treated. We investigated the feasibility of lymphatic mapping to image lymph nodes at risk for (micro)metastases in LACC and assessed the radiotherapy dose on the nodes at risk. METHODS: Patients with LACC were included between July 2020 and July 2022. Inclusion criteria were: ≥ 18 years old, intended curative chemoradiotherapy, investigation under anesthesia. Exclusion criteria were: pregnancy and extreme obesity. All patients underwent abdominal MRI, [18F]FDG-PET/CT and lymphatic mapping after administration of 6-8 depots of 99mTc]Tc-nanocolloid followed by planar and SPECT/CT images 2-4 and 24 h post-injection. RESULTS: Seventeen patients participated. In total, 40 nodes at risk were visualized on the lymphatic map in 13/17 patients with a median of two [range 0-7, IQR 0.5-3] nodes per patient, with unilateral drainage in 4/13 and bilateral drainage in 9/13 patients. No complications occurred. The lymphatic map showed more nodes compared to suspicious nodes on MRI or [18F]FDG-PET/CT in 8/14 patients. Sixteen patients were treated with radiotherapy with 34 visualized nodes on the lymphatic map. Of these nodes, 20/34 (58.8%) received suboptimal radiotherapy: 7/34 nodes did not receive radiotherapy at all, and 13/34 received external beam radiotherapy (EBRT), but no simultaneous integrated boost (SIB). CONCLUSION: Lymphatic mapping is feasible in LACC. Almost 60% of nodes at risk received suboptimal treatment during chemoradiation. As treatment failure could be caused by (micro)metastasis in some of these nodes, including nodes at risk in the radiotherapy treatment volume could improve radiotherapy treatment outcome in LACC. Trail registration The study was first registered at the International Clinical Trial Registry Platform (ICTRP) under number of NL9323 on 4 March 2021. Considering the source platform was not operational anymore, the study was retrospectively registered again on February 27, 2023 at CilicalTrials.gov under number of NCT05746156.
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PURPOSE: Imaging is essential in detecting lymph node metastases for radiotherapy treatment planning in locally advanced cervical cancer (LACC). There are not many data on the performance of [18F]FDG-PET(CT) in showing lymph node metastases in LACC. We pooled sensitivity and specificity of [18F]FDG-PET(CT) for detecting pelvic and/or para-aortic lymph node metastases in patients with LACC. Also, the positive and negative posttest probabilities at high and low levels of prevalence were determined. METHODS: MEDLINE and EMBASE searches were performed and quality characteristics assessed. Logit-sensitivity and logit-specificity estimates with corresponding standard errors were calculated. Summary estimates of sensitivity and specificity with corresponding 95% confidence intervals (CIs) were calculated by anti-logit transformation. Positive and negative likelihood ratios (LRs) were calculated from the mean logit-sensitivity and mean logit-specificity and the corresponding standard errors. The posttest probabilities were determined by Bayesian approach. RESULTS: Twelve studies were included with a total of 778 patients aged 10-85 years. For pelvic nodes, summary estimates of sensitivity, specificity, LR+ and LR- were: 0.88 (95%CI: 0.40-0.99), 0.93 (95%CI: 0.85-0.97), 11.90 (95%CI: 5.32-26.62) and 0.13 (95%CI: 0.01-1.08). At the lowest prevalence of 0.15 the positive predictive value (PPV) and negative predictive value (NPV) were 0.68 and 0.98, at the highest prevalence of 0.65, 0.96 and 0.81. For the para-aortic nodes, the summary estimates of sensitivity, specificity LR+ and LR- were: 0.40 (95%CI: 0.18-0.66), 0.93 (95%CI: 0.91-0.95), 6.08 (95%CI: 2.90-12.78) and 0.64 (95%CI: 0.42-0.99), respectively. At the lowest prevalence of 0.17 the PPV and NPV were 0.55 and 0.88, at the highest prevalence of 0.50, 0.86 and 0.61. CONCLUSION: The PPV and NPV of [18F]FDG-PET(CT) showing lymph node metastases in patients with LACC improves with higher prevalence. Prevalence and predictive values should be taken into account when determining therapeutic strategies based on [18F]FDG-PET(CT).
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Metástase Linfática/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Neoplasias do Colo do Útero/diagnóstico por imagem , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Feminino , Fluordesoxiglucose F18/uso terapêutico , Humanos , Metástase Linfática/patologia , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Compostos Radiofarmacêuticos/uso terapêutico , Neoplasias do Colo do Útero/patologia , Adulto JovemRESUMO
BACKGROUND: In patients with advanced stage cancer of the uterine cervix who undergo irradiation with curative intent, there is the necessity to treat all suspicious nodes on imaging. Our hypothesis was that adding fluorodeoxyglucose positron emission computer tomography/computer tomography (FDG-PET/CT) to the imaging workup would alter the external beam radiotherapy (EBRT) treatment plan, either resulting in an extended external beam radiotherapy (EBRT) field to the para-aortal region or an additional boost to suspicious nodes. Since extended field radiotherapy or additional boost can cause toxicity, our secondary aim was to assess the incidence of severe late bowel toxicity in patients treated with extended para-aortal EBRT-field and boost compared to elective pelvic radiotherapy. METHODS: Eighty-eight patients were enrolled. First, the optimal radiation treatment plan (EBRT and boost) was retrospectively determined based on magnetic resonance imaging (MRI) or FDG-PET/CT. Second, the severe bowel toxicity caused by the extended para-aortal field was assessed, based on the executed radiotherapy. RESULTS: Based on MRI 8/88 patients would receive EBRT with para-aortic extension, this was 21/88 for FDG-PET/CT. Based on MRI 47/704 lymph node regions would receive additional boost, while based on PET/CT 91/704. Late severe bowel toxicity was seen in 12/84 patients, 6/65 in the group who received elective pelvic irradiation and 6/19 with para-aortal EBRT and boost at common iliac and/or para-aortal lymph nodes. Significant worse overall survival was seen of patients who needed para-aortal irradiation. CONCLUSIONS: Addition of FDG-PET/CT leads to an extension of the elective EBRT volume and more suspicious lymph nodes receive a boost. However, when deciding to intensify radiation therapy, late severe bowel toxicity has to be taken into account.
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Fluordesoxiglucose F18 , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Radioterapia Guiada por Imagem , Neoplasias do Colo do Útero/diagnóstico por imagem , Neoplasias do Colo do Útero/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Metástase Linfática , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Retrospectivos , Análise de Sobrevida , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/cirurgiaRESUMO
[This corrects the article DOI: 10.1371/journal.pone.0120927.].
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AIM: Planar myocardial 123I-meta-iodobenzylguanidine (123I-mIBG) scintigraphy is a highly reproducible technique. However, differences in collimator use are one of the most important factors that cause variation among institutions and studies in heart-to-mediastinum (H/M) ratio. Therefore, standardization among various gamma camera-collimator combinations is needed. Previously, a phantom has been developed to cross-calibrate different acquisition conditions in Japan. For further cross-calibration of European myocardial 123I-mIBG imaging, the aim of this study was to collect 123I-mIBG data for H/M ratios from common European gamma camera vendors. METHODS: 210 experiments were performed in 27 European institutions. Based on these experiments, conversion coefficients for each gamma camera-collimator combination were calculated. An averaged conversion coefficient of 0.88 was used to calculate a standardized H/M ratio. RESULTS: On average, LE-collimator-derived H/M ratios were significantly lower compared to ME-collimator-derived H/M ratios. The mean conversion coefficients ranged from 0.553 to 0.605 for the LE-collimator group and from 0.824 to 0.895 for the ME-collimator group. CONCLUSION: Clinically established H/M ratios can be converted into standardized H/M ratios using cross-calibrated conversion coefficients. This standardization is important for identifying appropriate thresholds for adequate risk stratification. In addition, this cross-calibration enables comparison between different national and international data.
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3-Iodobenzilguanidina , Imagens de Fantasmas , Compostos Radiofarmacêuticos , Calibragem , Câmaras gama , Humanos , Valores de ReferênciaRESUMO
AIM: The NET, encoded by SLC6A2, is responsible for presynaptic NE-reuptake. 123I-mIBG is clinically used to evaluate cardiac sympathetic function. However, it is unknown if polymorphism of SLC6A2 influences cardiac sympathetic activity as assessed with 123I-mIBG. Therefore we studied the influence of SLC6A2 SNPs on myocardial 123I-mIBG parameters in CHF. MATERIALS AND METHODS: Forty-nine adults with stable CHF (age 66.5 ± 8.1 years, LVEF 22.3 ± 6.4) were enrolled. Fifteen minutes (early) and 4 hours (late) after administration of 123I-mIBG planar images were acquired. The H/M ratio was calculated from the manually drawn ROI over the left ventricle and a fixed mediastinal ROI. Fourteen exons of the SLC6A2 gene were analyzed from whole blood samples. RESULTS: We found 6 different SLC6A2 SNPs, although none were functional. LVEF was the only independent predictor for early (adjusted R 2 = 0.063, p = 0.045) and late H/M ratio (adjusted R 2 = 0.116, p = 0.010). NT-proBNP was the only independent predictor for 123I-mIBG WO (adjusted R 2 = 0.074, p = 0.032). SLC6A2 SNPs were not associated with any myocardial 123I-mIBG-derived parameter. CONCLUSION: In this specific CHF population polymorphism of SLC6A2 gene was not associated with any 123I-mIBG derived parameters.
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3-Iodobenzilguanidina , Insuficiência Cardíaca/diagnóstico por imagem , Insuficiência Cardíaca/genética , Proteínas da Membrana Plasmática de Transporte de Norepinefrina/genética , Polimorfismo Genético/genética , Cintilografia , Idoso , Doença Crônica , Feminino , Humanos , Radioisótopos do Iodo , Masculino , Pessoa de Meia-Idade , Compostos Radiofarmacêuticos , Volume SistólicoRESUMO
AIM: Chronic heart failure (CHF) results in both increased cardiac sympathetic activity and myocardial inflammation. The aim of this study was to identify the relationship between severity of heart failure (i.e., NT-proBNP and LVEF), cardiac sympathetic activity (123I-mIBG scintigraphy), and measures of inflammation in subjects with stable, optimally treated CHF. In addition, the predictive value for cardiac events (i.e., ventricular arrhythmia, progression of CHF and cardiac death) of 123I-mIBG parameters and these inflammatory markers was evaluated. MATERIALS AND METHODS: Fifty-five CHF patients (age 66.3 ± 8.0 years, 78% male, LVEF 22.4 ± 6.3) referred for cardiac 123I-mIBG imaging were included. At 15 minutes (early) and 4 hours (late) after i.v. administration of 123I-mIBG (185 MBq), planar images were acquired. Early Heart/Mediastinum (H/M) ratio, late H/M ratio, and 123I-mIBG washout (WO) were calculated. NT-proBNP and markers of inflammation (i.e., C-reactive protein (CRP), IL-1ß, IL-6, IL-8, IL-10, IL-12p40, tumor necrosis factor-α (TNF-α), soluble (s)E-selectin, myeloperoxidase (MPO), plasminogen activator inhibitor-1 (PAI-1), tPA, tumor necrosis factor receptor (TNFR) 1 and 2, and interferon (IFN) α and ß) were measured in blood plasma samples, taken just before 123I-mIBG administration. RESULTS: Mean early H/M ratio was 2.12 ± 0.39, late H/M ratio was 1.84 ± 0.40, and 123I-mIBG WO was 13.0 ± 10.9. LVEF was the only independent predictor of late H/M ratio (adjusted R 2 = 0.100, p = 0.011). NT-proBNP was an independent predictor of 123I-mIBG WO (adjusted R 2 = 0.090, p = 0.015). CRP, IL12p40, TNF-α, sE-selectin, MPO, PAI-1, tPA, and TNFR2 were not related to late H/M ratio and 123I-mIBG WO. During a median follow-up of 34 months (2-58 months), 13 patients experienced a cardiac event [ventricular arrhythmia (4), progression of CHF (4), and cardiac death (5)]. Univariate Cox regression analysis showed that the risk of a cardiac event was associated with CRP (HR 1.047 [1.013-1.081]), NT-proBNP (HR 1.141 [1.011-1.288]), MPO (HR 0.998 [0.996-1.000]), and late H/M ratio (HR 0.182 [0.035-0.946]). Multivariate Cox regression analysis showed that only CRP, NT-proBNP, MPO, and IL-12p40 were predictors of a cardiac event. CONCLUSION: Inflammation and cardiac sympathetic activity seem not to be related in stable CHF patients. This is corroborated by the finding that they both provide prognostic information in this specific CHF population. The current findings should be regarded as insightful but preliminary.
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3-Iodobenzilguanidina , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/diagnóstico por imagem , Cintilografia , Compostos Radiofarmacêuticos , Idoso , Biomarcadores/sangue , Doença Crônica , Feminino , Insuficiência Cardíaca/sangue , Humanos , Inflamação , Radioisótopos do Iodo , Masculino , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Valor Preditivo dos Testes , Prognóstico , Volume SistólicoRESUMO
BACKGROUND: 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) has proven to have a high diagnostic accuracy for the detection of bone infections. In patients with delayed union it may be clinically important to differentiate between aseptic and septic delayed union. The aim of this study was to evaluate the efficacy and to assess the optimal diagnostic accuracy of FDG-PET/CT in differentiating between aseptic and septic delayed union in the lower extremity. METHODS: This is a retrospective study of consecutive patients who underwent FDG-PET/CT scanning for suspicion of septic delayed union of the lower extremity. Diagnosis of aseptic delayed union or septic delayed union was made based on surgical deep cultures following PET/CT scanning and information on clinical follow-up. FDG-uptake values were measured at the fractured site by use of the maximum standardized uptake value (SUVmax). Sensitivity, specificity and diagnostic accuracy of FDG-PET/CT were calculated at various SUVmax cut-off points. RESULTS: A total of 30 patients were included; 13 patients with aseptic delayed unions and 17 patients with septic delayed unions. Mean SUVmax in aseptic delayed union patients was 3.23 (SD ± 1.21). Mean SUVmax in septic delayed union patients was 4.77 (SD ± 1.87). A cut-off SUVmax set at 4.0 showed sensitivity, specificity and diagnostic accuracy of FDG-PET/CT were 65, 77 and 70% to differentiate between aseptic and septic delayed union, respectively. CONCLUSION: Using a semi-quantitative measure (SUVmax) for interpretation of FDG-PET/CT imaging seems to be a promising tool for the discrimination between aseptic and septic delayed union.
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Fluordesoxiglucose F18/uso terapêutico , Extremidade Inferior/diagnóstico por imagem , Osteomielite/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Humanos , Estudos RetrospectivosRESUMO
Molecular imaging of matrix metalloproteinases (MMPs) may allow detection of atherosclerotic lesions vulnerable to rupture. In this study, we develop a novel radiolabelled compound that can target gelatinase MMP subtypes (MMP2/9) with high selectivity and inhibitory potency. Inhibitory potencies of several halogenated analogues of MMP subtype-selective inhibitors (N-benzenesulfonyliminodiacetyl monohydroxamates and N-halophenoxy-benzenesulfonyl iminodiacetyl monohydroxamates) were in the nanomolar range for MMP2/9. The analogue with highest inhibitory potency and selectivity was radiolabelled with [123I], resulting in moderate radiochemical yield, and high radiochemical purity. Biodistribution studies in mice, revealed stabilization in blood 1 hour after intravenous bolus injection. Intravenous infusion of the radioligand and subsequent autoradiography of excised aortas showed tracer uptake in atheroprone mice. Distribution of the radioligand showed co-localization with MMP2/9 immunohistochemical staining. In conclusion, we have developed a novel selective radiolabeled MMP2/9 inhibitor, suitable for single photon emission computed tomography (SPECT) imaging that effectively targets atherosclerotic lesions in mice.
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Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Placa Aterosclerótica/diagnóstico por imagem , Animais , Feminino , Ligantes , Espectroscopia de Ressonância Magnética , Camundongos , Camundongos Endogâmicos C57BL , Ensaio Radioligante , Distribuição Tecidual , Tomografia Computadorizada de Emissão de Fóton ÚnicoRESUMO
AIM: Chronic heart failure (CHF) is a life-threatening clinical syndrome, partly due to sudden cardiac death (SCD). Implantable cardioverter defibrillators (ICD) for primary prevention of SCD have improved overall survival of CHF patients. However, a high percentage of patients never receives appropriate ICD therapy. This prospective multicentre study evaluated whether cardiac sympathetic activity assessed by 123I-mIBG scintigraphy could be helpful in selecting patients for ICD implantation. MATERIALS AND METHODS: 135 stable CHF subjects (age 64.5±9.3years, 79% male, LVEF 25±6%) referred for prophylactic ICD implantation were enrolled in 13 institutions. All subjects underwent planar and SPECT 123I-mIBG scintigraphy. Early and late heart-to-mediastinum (H/M) ratio, 123I-mIBG washout (WO) and late summed scores were calculated. The primary endpoint was appropriate ICD therapy. The secondary endpoint was defined as the combined endpoint of all first cardiac events: appropriate ICD therapy, progression of heart failure (HF) and cardiac death. RESULTS: During a median follow-up of 30months (6-68months), 24 subjects (17.8%) experienced a first cardiac event (appropriate ICD therapy [12], HF progression [6], cardiac death [6]). Late H/M ratio and defect size of 123I-mIBG SPECT were not associated with appropriate ICD therapy. However, late H/M ratio was independently associated with the combined endpoint (HR 0.135 [0.035-0.517], p=0.001). Post-hoc analysis showed that the combination of late H/M ratio (HR 0.461 [0.281-0.757]) and LVEF (HR 1.052 [1.021-1.084]) was significantly associated with freedom of appropriate ICD therapy (p<0.001). CONCLUSION: 123I-mIBG scintigraphy seems to be helpful in selecting CHF subjects who might not benefit from ICD implantation.
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3-Iodobenzilguanidina , Desfibriladores Implantáveis/tendências , Insuficiência Cardíaca/diagnóstico por imagem , Insuficiência Cardíaca/terapia , Compostos Radiofarmacêuticos , Idoso , Doença Crônica , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
RATIONALE: 123I-mIBG planar image heart-to-mediastinum ratios effectively risk-stratify heart failure (HF) patients. The value of single-photon emission computed tomographic (SPECT) imaging for identifying increased risk of ventricular arrhythmias is less clear. This study sought to determine if findings from simultaneous interpretation of 123I-mIBG and 99mTc-tetrofosmin SPECT are predictive of arrhythmic events (ArEs). METHODS: 123I-mIBG SPECT images from 622 patients with ischemic HF were presented in standard displays alongside 99mTc-tetrofosmin images. Consensus interpretations using a 17-segment model produced summed scores. Cox proportional hazards analyses related findings to adjudicated ArEs over 2 years. RESULTS: 471 patients had images adequate for total 17-segment scoring. There were 48 ArEs (10.2%). Neither 123I-mIBG nor 99mTc-tetrofosmin SPECT summed scores were univariate predictors. On multivariate proportional hazards analysis, the 123I-mIBG SPECT score was independently predictive of ArEs (HR: 0.975, 95% CI 0.951-0.999, P = 0.042), but HR<1 indicated that risk decreased with increasing score. This occurred because patients with intermediately abnormal SPECT studies had a higher likelihood of ArEs compared to patients with extensive abnormalities. CONCLUSIONS: The presumption of a monotonic increase in ArE risk with increasing summed 123I-mIBG SPECT score may not be correct as ischemic HF patients with abnormalities of intermediate extent appear at highest risk.
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3-Iodobenzilguanidina , Arritmias Cardíacas/diagnóstico por imagem , Arritmias Cardíacas/mortalidade , Insuficiência Cardíaca/diagnóstico por imagem , Insuficiência Cardíaca/mortalidade , Compostos Organofosforados , Compostos de Organotecnécio , Tomografia Computadorizada com Tomografia Computadorizada de Emissão de Fóton Único/métodos , Causalidade , Comorbidade , Feminino , Humanos , Incidência , Internacionalidade , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/diagnóstico por imagem , Isquemia Miocárdica/mortalidade , Prognóstico , Compostos Radiofarmacêuticos , Reprodutibilidade dos Testes , Fatores de Risco , Sensibilidade e Especificidade , Tomografia Computadorizada com Tomografia Computadorizada de Emissão de Fóton Único/estatística & dados numéricos , Taxa de SobrevidaRESUMO
AIM: 22q11.2 deletion syndrome (22q11.2DS) affects catechol-O-methyl-transferase (COMT), which involves the degradation of norepinephrine (NE). Clinically, adults with 22q11.2DS are at increased risk for sudden unexpected death. Although the causes are likely multifactorial, increased cardiac sympathetic activity with subsequent fatal arrhythmia, due to increased levels of NE, should be considered as a possible mechanism predisposing to this premature death. The purpose of this study was to determine whether cardiac sympathetic activity is increased in 22q11.2DS, both at baseline and following an acute NE depletion with alpha-methyl-para-tyrosine (AMPT). METHODS: Five adults with 22q11.2DS and five age- and sex-matched healthy controls underwent 2 sessions with either AMPT or placebo administration before (123)I-mIBG scintigraphy. Heart-to-mediastinum ratios (H/M) were determined from the images 15min (early) and 4h (late) after administration of (123)I-mIBG and the washout (WO) was calculated as an indicator of adrenergic drive. RESULTS: At baseline there were no significant differences in both early and late H/M between 22q11.2DS and controls. However, there was a significant difference in WO between 22q11.2DS and controls (-4.92±2.8 and -10.44±7.2, respectively; p=0.027), but a "negative WO" does not support an increased sympathetic drive. In addition there was a trend towards a higher late H/M after AMPT administration compared to baseline which was more pronounced in 22q11.2DS. CONCLUSION: This study for the first time suggests normal cardiac sympathetic activity in adults with 22q11.2DS assessed by (123)I-mIBG scintigraphy. Although there is a small difference in adrenergic drive compared to healthy subjects, this most likely does not explain the increased unexpected death rate in the 22q11.2 DS population.
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Síndrome de DiGeorge/diagnóstico por imagem , Coração/diagnóstico por imagem , Imagem de Perfusão do Miocárdio/métodos , alfa-Metiltirosina/administração & dosagem , 3-Iodobenzilguanidina/administração & dosagem , Adulto , Síndrome de DiGeorge/fisiopatologia , Feminino , Coração/fisiopatologia , Humanos , Interpretação de Imagem Assistida por Computador , Masculino , Compostos Radiofarmacêuticos/administração & dosagem , Adulto JovemRESUMO
INTRODUCTION: Fluorine-18 fluorodeoxyglucose (F-FDG) PET/computed tomography (CT) has proven to be a valuable imaging modality with high diagnostic accuracy for the detection of bone infections. However, the physiological uptake values for F-FDG in the long bones of the lower extremity have not been established yet. This hampers correct interpretation of a F-FDG-PET/CT scan. PURPOSE: The purpose of this study was to determine the physiological uptake values of F-FDG in the long bones of the lower extremities, including the femur and the tibia. PATIENTS AND METHODS: We retrospectively analyzed the F-FDG-PET/CT scan of 84 consecutive patients from our database. F-FDG uptake parameters included mean standardized uptake value (SUVmean) and maximum standardized uptake value (SUVmax). Both SUVs were determined in the diaphyseal region of the femur and the tibia. RESULTS: SUVmean for the femoral diaphysis was 0.46 [95% confidence interval (CI) 0.42-0.49] and SUVmax was 0.81 (95% CI 0.74-0.88). For the tibial diaphysis, SUVmean was 0.34 (95% CI 0.32-0.37) and SUVmax was 0.61 (95% CI 0.56-0.65). SUVmean and SUVmax of the femur were significantly higher than that of the tibia (both P<0.01). SUVs for men were not significantly different from that for women and did not discriminate between age classes. CONCLUSION: For a correct interpretation of the F-FDG-PET/CT scan, we have determined the F-FDG uptake values in the long bones of the femur and the tibia. A SUVmean less than 0.5 and a SUVmax less than 0.8 can be considered as normal bone, irrespective of sex or age.
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Doenças Ósseas/diagnóstico por imagem , Doenças Ósseas/metabolismo , Fêmur/metabolismo , Fluordesoxiglucose F18/farmacocinética , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Tíbia/metabolismo , Adulto , Fatores Etários , Feminino , Fêmur/diagnóstico por imagem , Humanos , Extremidade Inferior/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Especificidade de Órgãos , Compostos Radiofarmacêuticos/farmacocinética , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Fatores Sexuais , Tíbia/diagnóstico por imagem , Distribuição TecidualRESUMO
123I-meta-iodobenzylguanidine (123I-mIBG) scintigraphy has been established as an important technique to evaluate cardiac sympathetic function and it has been shown to be of clinical value, especially for the assessment of prognosis, in many cardiac diseases. The majority of 123I-mIBG scintigraphy studies have focused on patients with cardiac dysfunction due to hypertension, ischemic heart disease, or valvular disease. However less is known about the role of 123I-mIBG scintigraphy in primary cardiomyopathies. This overview shows the clinical value of 123I-mIBG scintigraphy in two types of primary cardiomyopathy: The genetic hypertrophic cardiomyopathy (HCM) and the acquired Tako-tsubo cardiomyopathy (TCM). Cardiac sympathetic activity is increased in HCM and correlates to the septal wall thickness and consequently to the LVOT obstruction. Moreover, increased cardiac sympathetic activity correlates with impaired diastolic and systolic LV function. In addition, 123I-mIBG scintigraphy may be useful for determining the risk of developing congestive heart failure and ventricular tachycardia in these patients. In TCM 123I-mIBG scintigraphy can be used to assess cardiac sympathetic hyperactivity. In addition, 123I-mIBG scintigraphy may identify those patients who are prone to TCM recurrence and may help to identify responders to individual (pharmacological) therapy.
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Since the publication of the European Association of Nuclear Medicine (EANM) procedural guidelines for radionuclide myocardial perfusion imaging (MPI) in 2005, many small and some larger steps of progress have been made, improving MPI procedures. In this paper, the major changes from the updated 2015 procedural guidelines are highlighted, focusing on the important changes related to new instrumentation with improved image information and the possibility to reduce radiation exposure, which is further discussed in relation to the recent developments of new International Commission on Radiological Protection (ICRP) models. Introduction of the selective coronary vasodilator regadenoson and the use of coronary CT-contrast agents for hybrid imaging with SPECT/CT angiography are other important areas for nuclear cardiology that were not included in the previous guidelines. A large number of minor changes have been described in more detail in the fully revised version available at the EANM home page: http://eanm.org/publications/guidelines/2015_07_EANM_FINAL_myocardial_perfusion_guideline.pdf .
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Imagem de Perfusão do Miocárdio/métodos , Guias de Prática Clínica como Assunto , Sociedades Médicas , Tomografia Computadorizada por Raios X/métodos , Adulto , Meios de Contraste , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/fisiopatologia , Relação Dose-Resposta a Droga , Exercício Físico , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade , Imagem Multimodal , Imagem de Perfusão do Miocárdio/efeitos adversos , Imagem de Perfusão do Miocárdio/instrumentação , Purinas/efeitos adversos , Purinas/farmacologia , Pirazóis/efeitos adversos , Pirazóis/farmacologia , Exposição à Radiação , Segurança , Software , Tomografia Computadorizada por Raios X/efeitos adversos , Tomografia Computadorizada por Raios X/instrumentação , Vasodilatadores/efeitos adversos , Vasodilatadores/farmacologiaRESUMO
OBJECTIVE: Longitudinal studies objectively evaluating changes in regional fat distribution of HIV-infected children assessed by whole body dual energy X-ray absorptiometry (DEXA) are scarce, whilst this long-term effect of HIV and antiretroviral therapy (cART) is an important issue in infected children in need for lifelong treatment. METHODS: We assessed regional fat distribution over time, measured with sequential DEXA-scans in HIV-infected children on cART in cohorts from South Africa (SA) and the Netherlands (NL), and in healthy controls (SA). Limb and trunk fat Z-scores were calculated with the lambda-mu-sigma (LMS) method. Multivariable linear regression models with mixed effects were used to investigate the effect of cART compounds on body fat distribution over time. RESULTS: In total, 218 children underwent 445 DEXA assessments with a median follow-up of 3.5 years. Fat mass in all limbs was decreased in HIV-infected children compared to controls (arm fat Z-score: coefficient -0.4813; P = 0.006, leg fat Z-score: coefficient -0.4345; P = 0.013). In the HIV-infected group, stavudine treatment was associated with lower subcutaneous fat mass (arm fat Z-score: coefficient -0.5838; P = 0.001), with an additional cumulative exposure effect (arm fat Z-score: coefficient -0.0867; P = 0.003). CONCLUSIONS: Our study shows that subcutaneous fat loss is still prevalent in HIV-infected children on cART, and is strongly associated with cumulative stavudine exposure. These results underline the need for early detection of subcutaneous fat loss and alternative treatment options for HIV-infected children globally.
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Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , Infecções por HIV/patologia , Gordura Subcutânea/diagnóstico por imagem , Absorciometria de Fóton , Criança , Pré-Escolar , Feminino , Humanos , Estudos Longitudinais , Masculino , Países Baixos , Estudos RetrospectivosRESUMO
BACKGROUND: (131)I-metaiodobenzylguanidine ((131) I-MIBG) has a significant anti-tumor effect against neuroblastoma (NBL). Topotecan (TPT) can act as a radio-sensitizer and can up-regulate (131) I-MIBG uptake in vitro in NBL. AIM: Determine the efficacy of the combination of (131) I-MIBG with topotecan in newly diagnosed high-risk (HR) NBL patients. METHODS: In a prospective, window phase II study, patients with newly diagnosed high-risk neuroblastoma were treated at diagnosis with two courses of (131) I-MIBG directly followed by topotecan (0.7 mg/m(2) for 5 days). After these two courses, standard induction treatment (four courses of VECI), surgery and myeloablative therapy (MAT) with autologous stem cell transplantation (ASCT) was given. Response was measured after two courses of (131) I-MIBG-topotecan and post MAT and ASCT. Hematologic toxicity and harvesting of stem cells were analysed. Topoisomerase-1 activity levels were analysed in primary tumor material. RESULTS: Sixteen patients were included in the study; median age was 2.8 years. MIBG administered activity (AA) (median and range) of the first course was 0.5 (0.4-0.6) GBq/kg (giga Becquerel/kilogram) and of the second course 0.4 (0.3-0.5) GBq/kg. The overall objective response rate (ORR) after 2 × MIBG/TPT was 57%, the primary tumor RR was 94%, and bone marrow RR was 43%. The ORR post MAT and ASCT was 57%. Hematologic grade four toxicity: after first and second (131) I-MIBG (platelets 25/33%, neutrophils 13/33%, and hemoglobin 25/7%). Topoisomerase-1 activity levels were increased in 10/10 (100%) measured tumors. CONCLUSIONS: Combination therapy with MIBG-topotecan is an effective window treatment in newly diagnosed high-risk neuroblastoma patients.
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Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neuroblastoma/terapia , Transplante de Células-Tronco , Condicionamento Pré-Transplante , 3-Iodobenzilguanidina/administração & dosagem , Adolescente , Autoenxertos , Criança , Pré-Escolar , Terapia Combinada/métodos , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Neuroblastoma/mortalidade , Estudos Prospectivos , Fatores de Risco , Topotecan/administração & dosagemRESUMO
OBJECTIVES: The objective of this study was to determine the predictive value of C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) to a positive fluorine-18 fluorodeoxyglucose ((18)F-FDG) PET/computed tomography (CT) result in patients with inflammation of unknown origin and fever of unknown origin. PATIENTS AND METHODS: Individual data of 498 patients were retrieved from three retrospective studies. Receiver operating characteristic derived areas under the curve were used to assess (18)F-FDG PET/CT versus age, CRP, and ESR. The discriminative value of age, CRP, and ESR related to (18)F-FDG PET/CT was examined using the net reclassification improvement (NRI). RESULTS: A diagnosis was established in 331 patients; (18)F-FDG PET/CT had a diagnostic accuracy of 89%. (18)F-FDG PET/CT had the highest area under the curve (0.89, P<0.001). The addition of (18)F-FDG PET/CT to a diagnosis prediction model including age, CRP, and ESR resulted in an NRI of 42% (P<0.001). In the same model with CRP values below 20 mg/l or ESR values below 20 mm/h, the NRI was 64% (P<0.001) and 29% (P=0.059), respectively. In 30 of 91 patients with CRP less than 10 mg/l, a diagnosis could be established; (18)F-FDG PET/CT was 100% true negative only in patients with CRP levels less than 5 mg/l. CONCLUSION: In patients with fever of unknown origin or inflammation of unknown origin, compared with elevated ESR levels, elevated CRP levels more often indicate a true positive (18)F-FDG PET/CT outcome.In addition, (18)F-FDG PET/CT, compared with CRP and ESR, shows the highest discrimination of patients with possible disabling disease.
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Proteína C-Reativa/metabolismo , Febre de Causa Desconhecida/sangue , Febre de Causa Desconhecida/diagnóstico , Fluordesoxiglucose F18 , Imagem Multimodal , Tomografia por Emissão de Pósitrons , Tomografia Computadorizada por Raios X , Adulto , Idoso , Sedimentação Sanguínea , Feminino , Febre de Causa Desconhecida/diagnóstico por imagem , Febre de Causa Desconhecida/metabolismo , Humanos , Inflamação/sangue , Inflamação/diagnóstico por imagem , Inflamação/metabolismo , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Curva ROC , Estudos RetrospectivosRESUMO
PURPOSE: The aim of this study was to find clinically relevant MIBG-avid metastatic patterns in patients with newly diagnosed stage 4 neuroblastoma. METHODS: Diagnostic (123)I-MIBG scans from 249 patients (123 from a European and 126 from the COG cohort) were assessed for metastatic spread in 14 body segments and the form of the lesions: "focal" (clear margins distinguishable from adjacent background) or "diffuse" (indistinct margins, dispersed throughout the body segment). The total numbers of diffuse and focal lesions were recorded. Patients were then categorized as having lesions exclusively focal, lesions more focal than diffuse, lesions more diffuse than focal, or lesions exclusively diffuse. RESULTS: Diffuse lesions affected a median of seven body segments and focal lesions a median of two body segments (P < 0.001, both cohorts). Patients with a focal pattern had a median of 2 affected body segments and those with a diffuse pattern a median of 11 affected body segments (P < 0.001, both cohorts). Thus, two MIBG-avid metastatic patterns emerged: "limited-focal" and "extensive-diffuse". The median numbers of affected body segments in MYCN-amplified (MNA) tumours were 5 (European cohort) and 4 (COG cohort) compared to 9 and 11, respectively, in single-copy MYCN (MYCNsc) tumours (P < 0.001). Patients with exclusively focal metastases were more likely to have a MNA tumour (60% and 70%, respectively) than patients with the other types of metastases (23% and 28%, respectively; P < 0.001). In a multivariate Cox regression analysis, focal metastases were associated with a better event-free and overall survival than the other types of metastases in patients with MNA tumours in the COG cohort (P < 0.01). CONCLUSION: Two metastatic patterns were found: a "limited and focal" pattern found mainly in patients with MNA neuroblastoma that correlated with prognosis, and an "extensive and diffuse" pattern found mainly in patients with MYCNsc neuroblastoma.
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3-Iodobenzilguanidina , Neuroblastoma/diagnóstico por imagem , Proteínas Nucleares/genética , Proteínas Oncogênicas/genética , Compostos Radiofarmacêuticos , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Imagem Multimodal , Proteína Proto-Oncogênica N-Myc , Metástase Neoplásica/diagnóstico por imagem , Metástase Neoplásica/genética , Metástase Neoplásica/patologia , Neuroblastoma/genética , Neuroblastoma/patologia , Tomografia por Emissão de Pósitrons , Valor Preditivo dos Testes , Prognóstico , Tomografia Computadorizada por Raios XRESUMO
AIMS: We sought to compare the diagnostic accuracy of basal stenosis resistance index (BSR), instantaneous wave-free ratio (iFR) and fractional flow reserve (FFR) for stenosis-specific myocardial ischaemia identified by means of a combined reference standard of myocardial perfusion scintigraphy and the hyperaemic stenosis resistance index. METHODS AND RESULTS: BSR and FFR were determined for 299 coronary stenoses, iFR was determined for 85 coronary stenoses (iFR cohort). The discriminative value for stenosis-specific myocardial ischaemia was compared by means of the area under the receiver operating characteristic (ROC) curves (AUC). Classification agreement with the reference standard was determined according to ROC curve-derived ischaemic cut-off values, as well as according to clinical cut-off values, equivalent to the 0.80 FFR cut-off. Across all stenoses, the discriminative value of BSR and FFR was equivalent (AUC: 0.90 and 0.91, respectively, p=0.46). In the iFR cohort, the discriminative value was equivalent for BSR, iFR, and FFR (AUC: 0.88, 0.84, and 0.88, respectively; p≥0.20 for all). At both ischaemic as well as clinical cut-off values, classification agreement with the reference standard was equivalent for BSR and FFR across all stenoses, as well as for BSR, iFR, and FFR in the iFR cohort. CONCLUSIONS: BSR, iFR, and FFR have equivalent diagnostic accuracy for the detection of ischaemia-generating coronary stenoses.