RESUMO
BACKGROUND: Gastroenteropancreatic neuroendocrine neoplasms (GEPNENs) are heterogeneous in clinical course, biology, and outcomes. The NETPET score predicts survival by scoring uptake on dual [68Ga]DOTATATE and [18F]FDG PET/CT scans. We aimed to validate previous single-centre findings in a multicentre, international study. METHODS: Dual scans were assigned a NETPET score of P1 (DOTATATE positive/FDG negative), P2-4 (DOTATATE positive/FDG positive), or P5 (DOTATATE negative/FDG positive). NETPET score, histological grade, age at diagnosis, and presence/absence of extrahepatic disease were compared to overall survival/time to progression on univariate and multivariate analysis. RESULTS: 319 metastatic/unresectable GEPNEN patients were included. The NETPET score was significantly associated with overall survival and time to progression on univariate and multivariate analysis (all p < 0.01). Median overall survival/time to progression was 101.8/25.5 months for P1, 46.5/16.7 months for P2-4, and 11.5/6.6 months for P5. Histological grade correlated with overall survival and time to progression on univariate and multivariate analysis (all p < 0.01), while presence/absence of extrahepatic disease did not. Age at diagnosis correlated with overall survival on univariate and multivariate analysis (p < 0.01). The NETPET score also correlated with histological grade (p < 0.001). CONCLUSION: This study validates the NETPET score as a prognostic biomarker in metastatic GEPNENs, capturing the complexity of dual PET imaging.
Assuntos
Neoplasias Gastrointestinais , Tumores Neuroendócrinos , Compostos Organometálicos , Humanos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Fluordesoxiglucose F18 , Radioisótopos de Gálio , Tomografia por Emissão de Pósitrons , Tumores Neuroendócrinos/patologiaRESUMO
PURPOSE: To quantify the effects of absorbed radiation dose on healthy liver parenchyma following radioembolisation (RE) using [99mTc]TcMebrofenin to analyse both global and regional liver function. METHODS: Patients having RE to treat hepatic disease underwent a [99mTc]TcMebrofenin hepatobilliary scintigraphy (HBS) study at both baseline and 8 weeks following treatment. Changes in global liver uptake rate were compared with healthy liver absorbed dose measures derived from the post-treatment 90Y PET/CT, including average dose, minimum dose to 70% of the volume (D70) and volume receiving at least 50 Gy (V50). Changes in functional burden associated with treatment and spared liver volumes in patients receiving lobar RE were also assessed, as were changes experienced by regional volumes corresponding to various dose ranges. Standard liver function pathology tests (LFTs) (bilirubin, albumin, ALP, AST, ALT and GGT) were examined for changes between baseline and post-treatment. RESULTS: Thirty-five patients were included in the study, of which, 9 had lobar treatment. A significant linear correlation was found between both baseline global liver uptake rate (negative) and D70 with change in global liver uptake rate. Patients undergoing lobar treatments demonstrated a shift in functional burden, and a significant difference was seen between the mean dose corresponding to liver volumes that increased their functional burden (9 Gy) and those that decreased their functional burden (35 Gy). No baseline LFTs predicted a decrease in global liver function; however, D70 demonstrated a linear correlation with changes in bilirubin and GGT. CONCLUSIONS: Given the significant negative relationship between baseline and change in global liver uptake rate, baseline HBS studies should not be used alone to disqualify patients considered for RE. In terms of treatment planning and evaluation, D70 may be the most appropriate metric of dose, with values greater than 15 Gy indicative of a likely drop in global liver function. The evidence of increasing functional burden in spared liver volumes suggests that patients at risk of complications could benefit from a lobar approach to treatment.
Assuntos
Neoplasias Hepáticas , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Humanos , Fígado/diagnóstico por imagem , Testes de Função Hepática , Neoplasias Hepáticas/diagnóstico por imagem , Cintilografia , Compostos RadiofarmacêuticosRESUMO
INTRODUCTION: 18-Fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) avidity in neuroendocrine neoplasms (NENs) has been associated with higher-grade disease. 18F-FDG avidity and high SUVmax have been demonstrated to predict poor outcome. Quantitative metrics of 18F-FDG PET, specifically metabolic tumour volume (MTV) and total lesion glycolysis (TLG), have been shown to be prognostic factors in other malignancies, but these have not been investigated to date in NENs. METHODS: Patients with NEN undergoing 18F-FDG at Royal North Shore Hospital from 2012 to 2018 were included. Images were analysed with automated segmentation (SUV cut-off of 4) followed by contour verification by a nuclear medicine physician and manual segmentation where required. Variables collected included patient age, histological grade, MTV, TLG, and SUVmax/SUVmean. The primary outcome was overall survival (OS), and the secondary outcome was progression-free survival (PFS). Univariate (UV) and multivariate (MV) analyses were performed for OS and PFS for MTV and TLG separately. For UV analysis, the median MTV and TLG were used to dichotomise the cohort. MTV/TLG for NENs of different histological grade were compared using ANOVA. RESULTS: One hundred and ninety patients were included (median age 63.5, 49% female). Primary site: 42% small bowel, 32% pancreas, 15% other gastrointestinal, 6% lung, 6% other. Grade for gastroenteropancreatic NENs and bronchial NEN: G1/typical carcinoid 37%, G2/atypical carcinoid 40%, G3/large-cell/small-cell neuroendocrine carcinoma 16%, unknown 8%. Median MTV was 4.83 mL (range 0-3,161 mL) and median TLG was 29.22. Patients with high MTV had worse median OS compared to those with low MTV (29.7 months vs. not reached, HR 4.1, 95% CI 2.25-7.49, p < 0.00001). Considered as a continuous variable, MTV predicted for poorer OS on UV (p < 0.00001) and MV (p = 0.003) analyses. Whilst histological grade was significant on both UV and MV, SUVmax was significant on UV (p < 0.00001) but not MV (p = 0.76). Tumours of higher grade had higher MTV (mean MTV - G1: 39.6 mL, G2: 107 mL, G3: 337 mL; p = 0.0001 by ANOVA). CONCLUSIONS: Quantitative analysis of 18F-FDG PET in NEN is feasible. High MTV/TLG are predictors of poor prognosis in NEN. Further analyses are underway to investigate a larger cohort of NEN patients.
Assuntos
Fluordesoxiglucose F18 , Tumores Neuroendócrinos/diagnóstico por imagem , Tumores Neuroendócrinos/metabolismo , Tumores Neuroendócrinos/mortalidade , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons/métodos , Tomografia por Emissão de Pósitrons/normas , Prognóstico , Estudos Retrospectivos , Análise de SobrevidaRESUMO
BACKGROUND: Accurate staging of patients with prostate cancer (PCa) is important for therapeutic decision-making. Relapse after surgery or radiotherapy of curative intent is not uncommon and, in part, represents a failure of staging with current diagnostic imaging techniques to detect disease spread. Prostate-specific membrane antigen (PSMA) positron-emission tomography (PET)/computed tomography (CT) is a new whole-body scanning technique that enables visualization of PCa with high contrast. The hypotheses of this study are that: (i) PSMA-PET/CT has improved diagnostic performance compared with conventional imaging; (ii) PSMA-PET/CT should be used as a first-line diagnostic test for staging; (iii) the improved diagnostic performance of PSMA-PET/CT will result in significant management impact; and (iv) there are economic benefits if PSMA-PET/CT is incorporated into the management algorithm. OBJECTIVES AND METHODS: The proPSMA trial is a prospective, multicentre study in which patients with untreated high-risk PCa will be randomized to gallium-68-PSMA-11 PET/CT or conventional imaging, consisting of CT of the abdomen/pelvis and bone scintigraphy with single-photon emission CT/CT. Patients eligible for inclusion are those with newly diagnosed PCa with select high-risk features, defined as International Society of Urological Pathology grade group ≥3 (primary Gleason grade 4, or any Gleason grade 5), prostate-specific antigen level ≥20 ng/mL or clinical stage ≥T3. Patients with negative, equivocal or oligometastatic disease on first line-imaging will cross over to receive the other imaging arm. The primary objective is to compare the accuracy of PSMA-PET/CT with that of conventional imaging for detecting nodal or distant metastatic disease. Histopathological, imaging and clinical follow-up at 6 months will define the primary endpoint according to a predefined scoring system. Secondary objectives include comparing management impact, the number of equivocal studies, the incremental value of second-line imaging in patients who cross over, the cost of each imaging strategy, radiation exposure, inter-observer agreement and safety of PSMA-PET/CT. Longer-term follow-up will also assess the prognostic value of a negative PSMA-PET/CT. OUTCOME AND SIGNIFICANCE: This trial will provide data to establish whether PSMA-PET/CT should replace conventional imaging in the primary staging of select high-risk localized PCa, or whether it should be used to provide incremental diagnostic information in selected cases.
Assuntos
Antígenos de Superfície/metabolismo , Meios de Contraste/uso terapêutico , Radioisótopos de Gálio/uso terapêutico , Glutamato Carboxipeptidase II/metabolismo , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Neoplasias da Próstata/diagnóstico por imagem , Compostos Radiofarmacêuticos/uso terapêutico , Antígenos de Superfície/análise , Meios de Contraste/química , Glutamato Carboxipeptidase II/análise , Humanos , Masculino , Estadiamento de Neoplasias , Estudos Prospectivos , Próstata/diagnóstico por imagem , Neoplasias da Próstata/terapia , Compostos Radiofarmacêuticos/químicaRESUMO
BACKGROUND: TargomiRs are minicells (EnGeneIC Dream Vectors) loaded with miR-16-based mimic microRNA (miRNA) and targeted to EGFR that are designed to counteract the loss of the miR-15 and miR-16 family miRNAs, which is associated with unsuppressed tumour growth in preclinical models of malignant pleural mesothelioma. We aimed to assess the safety, optimal dosing, and activity of TargomiRs in patients with malignant pleural mesothelioma. METHODS: In this first-in-man, open-label, dose-escalation phase 1 trial at three major cancer centres in Sydney (NSW, Australia), we recruited adults (aged ≥18 years) with a confirmed diagnosis of malignant pleural mesothelioma, measurable disease, radiological signs of progression after previous chemotherapy, Eastern Cooperative Oncology Group performance status of 0 or 1, life expectancy of 3 months or more, immunohistochemical evidence of tumour EGFR expression, and adequate bone marrow, liver, and renal function. Patients were given TargomiRs via 20 min intravenous infusion either once or twice a week (3 days apart) in a traditional 3â+â3 dose-escalation design in five dose cohorts. The dose-escalation steps planned were 5â×â109, 7â×â109, and 9â×â109 TargomiRs either once or twice weekly, but after analysis of data from the first eight patients, all subsequent patients started protocol treatment at 1â×â109 TargomiRs. The primary endpoints were to establish the maximum tolerated dose of TargomiRs as measured by dose-limiting toxicity, define the optimal frequency of administration, and objective response (defined as the percentage of assessable patients with a complete or partial response), duration of response (defined as time from the first evidence of response to disease progression in patients who achieved a response), time to response (ie, time from start of treatment to the first evidence of response) and overall survival (defined as time from treatment allocation to death from any cause). Analyses were based on the full analysis set principle, including every patient who received at least one dose of TargomiRs. The study was closed for patient entry on Jan 3, 2017, and registered with ClinicalTrials.gov, number NCT02369198, and the Australian Registry of Clinical Trials, number ACTRN12614001248651. FINDINGS: Between Sept 29, 2014, and Nov 24, 2016, we enrolled 27 patients, 26 of whom received at least one TargomiR dose (one patient died before beginning treatment). Overall, five dose-limiting toxicities were noted: infusion-related inflammatory symptoms and coronary ischaemia, respectively, in two patients given 5â×â109 TargomiRs twice weekly; anaphylaxis and cardiomyopathy, respectively, in two patients given 5â×â109 TargomiRs once weekly but who received reduced dexamethasone prophylaxis; and non-cardiac pain in one patient who received 5â×â109 TargomiRs once weekly. We established that 5â×â109 TargomiRs once weekly was the maximum tolerated dose. TargomiR infusions were accompanied by transient lymphopenia (25 [96%] of 26 patients), temporal hypophosphataemia (17 [65%] of 26 patients), increased aspartate aminotransferase or alanine aminotranferase (six [23%] of 26 patients), and increased alkaline phosphatase blood concentrations (two [8%]). Cardiac events occurred in five patients: three patients had electrocardiographic changes, one patient had ischaemia, and one patient had Takotsubo cardiomyopathy. Of the 22 patients who were assessed for response by CT, one (5%) had a partial response, 15 (68%) had stable disease, and six (27%) had progressive disease. The proportion of patients who achieved an objective response was therefore one (5%) of 22, and the duration of the objective response in that patient was 32 weeks. Median overall survival was 200 days (95% CI 94-358). During the trial, 21 deaths occurred, of which 20 were related to tumour progression and one was due to bowel perforation. INTERPRETATION: The acceptable safety profile and early signs of activity of TargomiRs in patients with malignant pleural mesothelioma support additional studies of TargomiRs in combination with chemotherapy or immune checkpoint inhibitors. FUNDING: Asbestos Diseases Research Foundation.
Assuntos
Neoplasias Pulmonares/tratamento farmacológico , Mesotelioma/tratamento farmacológico , MicroRNAs/administração & dosagem , Recidiva Local de Neoplasia/tratamento farmacológico , Segurança do Paciente , Neoplasias Pleurais/tratamento farmacológico , Adulto , Idoso , Austrália , Biópsia por Agulha , Institutos de Câncer , Intervalo Livre de Doença , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Seguimentos , Humanos , Imuno-Histoquímica , Infusões Intravenosas , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Dose Máxima Tolerável , Mesotelioma/diagnóstico por imagem , Mesotelioma/mortalidade , Mesotelioma/patologia , Mesotelioma Maligno , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Seleção de Pacientes , Neoplasias Pleurais/diagnóstico por imagem , Neoplasias Pleurais/mortalidade , Neoplasias Pleurais/patologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Medição de Risco , Análise de Sobrevida , Resultado do TratamentoRESUMO
PURPOSE: To investigate and compare the quantitative accuracy of (90)Y imaging across different generation PET/CT scanners, for the purpose of dosimetry after radioembolization with resin microspheres. METHODS: A strict experimental and imaging protocol was followed by 47 international sites using the NEMA 2007/IEC 2008 PET body phantom with an 8-to-1 sphere-to-background ratio of (90)Y solution. The phantom was imaged over a 7-day period (activity ranging from 0.5 to 3.0 GBq) and all reconstructed data were analysed at a core laboratory for consistent processing. Quantitative accuracy was assessed through measures of total phantom activity, activity concentration in background and hot spheres, misplaced counts in a nonradioactive insert, and background variability. RESULTS: Of the 69 scanners assessed, 37 had both time-of-flight (ToF) and resolution recovery (RR) capability. These current generation scanners from GE, Philips and Siemens could reconstruct background concentration measures to within 10% of true values over the evaluated range, with greater deviations on the Philips systems at low count rates, and demonstrated typical partial volume effects on hot sphere recovery, which dominated spheres of diameter <20 mm. For spheres >20 mm in diameter, activity concentrations were consistently underestimated by about 20%. Non-ToF scanners from GE Healthcare and Siemens were capable of producing accurate measures, but with inferior quantitative recovery compared with ToF systems. CONCLUSION: Current generation ToF scanners can consistently reconstruct (90)Y activity concentrations, but they underestimate activity concentrations in small structures (≤37 mm diameter) within a warm background due to partial volume effects and constraints of the reconstruction algorithm. At the highest count rates investigated, measures of background concentration (about 300 kBq/ml) could be estimated on average to within 1%, 5% and 2% for GE Healthcare (all-pass filter, RR + ToF), Philips (4i8s ToF) and Siemens (2i21s all-pass filter, RR + ToF) ToF systems, respectively. Over the range of activities investigated, comparable performance between GE Healthcare and Siemens ToF systems suggests suitability for quantitative analysis in a scenario analogous to that of postradioembolization imaging for treatment of liver cancer.
Assuntos
Embolização Terapêutica/métodos , Microesferas , Tomografia por Emissão de Pósitrons , Doses de Radiação , Compostos Radiofarmacêuticos , Tomografia Computadorizada por Raios X , Radioisótopos de Ítrio , Embolização Terapêutica/efeitos adversos , Humanos , Imagem Multimodal , Imagens de FantasmasRESUMO
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.
Assuntos
Processamento de Imagem Assistida por Computador/métodos , Imagem Multimodal/métodos , Tomografia por Emissão de Pósitrons/métodos , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Interpretação Estatística de Dados , Câmaras gama , Imagem Multimodal/instrumentação , Tomografia por Emissão de Pósitrons/instrumentação , Tomografia Computadorizada de Emissão de Fóton Único/instrumentação , Tomografia Computadorizada por Raios X/instrumentaçãoRESUMO
Objectives: To address the problem of using large volumes of long-lived radionuclides in test phantoms to check calibration accuracy of PET and SPECT systems we have developed a test object which (a) contains less radioactivity, (b) has a low total volume, and (c) is easier to store than currently used phantoms, while still making use of readily-available "standardised" test objects. Methods: We have designed a hollow acrylic cylindrical insert compatible with the NEMA/IEC PET Body Image Quality (IQ) phantom used in NU 2 performance testing of PET systems. The insert measures 90 mm internal diameter and 70 mm internal height and so is sufficiently large to not be subject to partial volume effects in PET or SPECT imaging. The volume of the insert is approximately 500 mL. It has been designed as a replacement for the standard long cylindrical "lung insert" in the IQ phantom without needing to remove the fillable hollow spheres of the phantom. The insert been tested with 18F, 68Ga and 124I PET/CT and 99mTc, 131I and 177Lu SPECT/CT on scanners that had previously been calibrated for these radionuclides. Results: The scanners were found to produce accurate image reconstructions in the insert with 5% of the true value without any confounding uncertainty from partial volume effects when compared to NEMA NU 2-2018 Phantom measurement. Conclusions: The "ARTnet Insert" is simple to use, inexpensive, compatible with current phantoms and is suitable for both PET and SPECT systems. It does not suffer from significant partial volume losses permitting its use even with the poor spatial resolution of high-energy imaging with 131I SPECT. Furthermore, it uses less radioactivity in a smaller volume than would be required to fill the entire phantom as is usually done. Long-term storage is practical while allowing radioactive decay of the insert contents.
RESUMO
OBJECTIVE: We investigated metabolic tumor volume (MTV) and total lesion glycolysis (TLG) on pre-treatment FDG-PET as prognostic markers for survival in patients with metastatic neuroendocrine neoplasms (NENs) receiving peptide receptor radionuclide therapy (PRRT). METHODS: A retrospective review of patients with metastatic NENs receiving PRRT was undertaken. Pre-treatment FDG-PET images were analyzed and variables collected included MTV and TLG (dichotomized by median into high vs low). Main Outcomes were overall survival (OS) and progression-free survival (PFS) by MTV and TLG (high vs low). RESULTS: One hundred five patients were included. Median age was 64 years (50% male). Main primary NEN sites were small bowel (43.8%) and pancreas (40.0%). Median MTV was 3.8 mL and median TLG was 19.9. Dichotomization formed identical cohorts regardless of whether MTV or TLG were used. Median OS was 72 months; OS did not differ based on MTV/TLG high versus low (47.4 months vs not reached; hazard ratio, 0.43; 95% confidence interval [CI], 0.18-1.04; P = 0.0594). Median PFS was 30.4 months; PFS differed based on MTV/TLG high versus low (21.6 months vs 45.7 months; hazard ratio, 0.35; 95% CI, 0.19-0.64; P = 0.007). CONCLUSIONS: Low MTV/TLG on pre-treatment FDG-PET was associated with longer PFS in metastatic NEN patients receiving PRRT.
Assuntos
Fluordesoxiglucose F18 , Tumores Neuroendócrinos , Octreotida , Compostos Organometálicos , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos , Carga Tumoral , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Tumores Neuroendócrinos/patologia , Tumores Neuroendócrinos/radioterapia , Tumores Neuroendócrinos/diagnóstico por imagem , Tumores Neuroendócrinos/metabolismo , Tumores Neuroendócrinos/mortalidade , Estudos Retrospectivos , Idoso , Octreotida/análogos & derivados , Octreotida/uso terapêutico , Tomografia por Emissão de Pósitrons/métodos , Prognóstico , Compostos Organometálicos/uso terapêutico , Adulto , Receptores de Peptídeos/metabolismo , Glicólise , Idoso de 80 Anos ou mais , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/radioterapia , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/mortalidade , Intervalo Livre de Progressão , Resultado do TratamentoRESUMO
[18F]FDG PET/CT and [68Ga]Ga-DOTATATE PET/CT are both used to predict tumor biology in neuroendocrine neoplasms. Although the presence of discordant ([18F]FDG-avid/non-[68Ga]Ga-DOTATATE-avid) disease predicts poor prognosis, the significance of the volume of such discordant disease remains undetermined. The aim of this study is to investigate discordant tumor volume as a potential biomarker in patients with advanced gastroenteropancreatic neuroendocrine neoplasms (GEPNENs). Methods: A multicenter retrospective study in patients with advanced GEPNENs and paired [18F]FDG and [68Ga]Ga-DOTATATE PET/CT no more than 85 d apart was conducted. Patients with discordant disease were identified by the NETPET score, and discordant lesions were contoured with a flat [18F]FDG SUV cutoff of 4. The primary variable of interest was the total discordant volume (TDV), which was the sum of the volumes of discordant lesions. Patients were dichotomized into high- and low-TDV cohorts by the median value. The primary endpoint was overall survival. Results: In total, 44 patients were included (50% men; median age, 60 y), with primary cancers in the pancreas (45%), small bowel (23%), colon (20%), and other (12%). Of the patients, 5% had grade 1 disease, 48% had grade 2 disease, and 48% had grade 3 disease (24% well differentiated, 67% poorly differentiated, 10% unknown within the grade 3 cohort). The overall median survival was 14.1 mo. Overall survival was longer in the low-TDV cohort than in the high-TDV cohort (median volume, 43.7 cm3; survival time, 23.8 mo vs. 9.4 mo; hazard ratio, 0.466 [95% CI, 0.229-0.948]; P = 0.0221). Patients with no more than 2 discordant intrahepatic lesions survived longer than those with 2 or more lesions (31.8 mo vs. 10.2 mo, respectively; hazard ratio, 0.389 [95% CI, 0.194-0.779]; P = 0.0049). Conclusion: TDV is a potential prognostic biomarker in GEPNENs and should be investigated in future neuroendocrine neoplasm trials.
Assuntos
Neoplasias Gastrointestinais , Tumores Neuroendócrinos , Compostos Organometálicos , Masculino , Humanos , Pessoa de Meia-Idade , Feminino , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Fluordesoxiglucose F18 , Radioisótopos de Gálio , Estudos Retrospectivos , Biomarcadores , Tumores Neuroendócrinos/diagnóstico por imagem , Tumores Neuroendócrinos/patologiaRESUMO
Ventilation and perfusion (V/Q) lung scintigraphy has been used in the assessment of patients with suspected pulmonary embolism for more than 50 y. Advances in imaging technology make SPECT and SPECT/CT feasible. This article will examine the application and technical considerations associated with performing 3-dimensional V/Q SPECT and the contribution of a coacquired CT scan. The literature tends to be mixed and contradictory in terms of appropriate investigation algorithms for pulmonary embolism. V/Q SPECT and SPECT/CT offer significant advantages over planar V/Q, with or without the advantages of Technegas ventilation, and if available should be the preferred option in the evaluation of patients with suspected pulmonary embolism.
Assuntos
Embolia Pulmonar , Tomografia Computadorizada de Emissão de Fóton Único , Humanos , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Tomografia Computadorizada por Raios X/métodos , Pulmão , Tomografia Computadorizada com Tomografia Computadorizada de Emissão de Fóton Único , Relação Ventilação-PerfusãoRESUMO
Our aim was to report the use of 64Cu and 67Cu as a theranostic pair of radionuclides in human subjects. An additional aim was to measure whole-organ dosimetry of 64Cu and 67Cu attached to the somatostatin analog octreotate using the sarcophagine MeCOSar chelator (SARTATE) in subjects with somatostatin receptor-expressing lesions confined to the cranium, thereby permitting normal-organ dosimetry for the remainder of the body. Methods: Pretreatment PET imaging studies were performed up to 24 h after injection of [64Cu]Cu-SARTATE, and normal-organ dosimetry was estimated using OLINDA/EXM. Subsequently, the trial subjects with multifocal meningiomas were given therapeutic doses of [67Cu]Cu-SARTATE and imaged over several days using SPECT/CT. Results: Five subjects were initially recruited and imaged using PET/CT before treatment. Three of the subjects were subsequently administered 4 cycles each of [67Cu]Cu-SARTATE followed by multiple SPECT/CT imaging time points. No serious adverse events were observed, and no adverse events led to withdrawal from the study or discontinuation from treatment. The estimated mean effective dose was 3.95 × 10-2 mSv/MBq for [64Cu]Cu-SARTATE and 7.62 × 10-2 mSv/MBq for [67Cu]Cu-SARTATE. The highest estimated organ dose was in spleen, followed by kidneys, liver, adrenals, and small intestine. The matched pairing was shown by PET and SPECT intrasubject imaging to have nearly identical targeting to tumors for guiding therapy, demonstrating a potentially accurate and precise theranostic product. Conclusion: 64Cu and 67Cu show great promise as a theranostic pair of radionuclides. Further clinical studies will be required to examine the therapeutic dose required for [67Cu]Cu-SARTATE for various indications. In addition, the ability to use predictive 64Cu-based dosimetry for treatment planning with 67Cu should be further explored.
Assuntos
Neoplasias Meníngeas , Meningioma , Humanos , Meningioma/diagnóstico por imagem , Meningioma/radioterapia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Radioisótopos , Radiometria , Compostos Radiofarmacêuticos/uso terapêutico , Distribuição TecidualRESUMO
Background: Glioblastoma (GBM) is the most aggressive type of brain cancer, with a 5-year survival rate of ~5% and most tumours recurring locally within months of first-line treatment. Hypoxia is associated with worse clinical outcomes in GBM, as it leads to localized resistance to radiotherapy and subsequent tumour recurrence. Current standard of care treatment does not account for tumour hypoxia, due to the challenges of mapping tumour hypoxia in routine clinical practice. In this clinical study, we aim to investigate the role of oxygen enhanced (OE) and blood-oxygen level dependent (BOLD) MRI as non-invasive imaging biomarkers of hypoxia in GBM, and to evaluate their potential role in dose-painting radiotherapy planning and treatment response assessment. Methods: The primary endpoint is to evaluate the quantitative and spatial correlation between OE and BOLD MRI measurements and [18F]MISO values of uptake in the tumour. The secondary endpoints are to evaluate the repeatability of MRI biomarkers of hypoxia in a test-retest study, to estimate the potential clinical benefits of using MRI biomarkers of hypoxia to guide dose-painting radiotherapy, and to evaluate the ability of MRI biomarkers of hypoxia to assess treatment response. Twenty newly diagnosed GBM patients will be enrolled in this study. Patients will undergo standard of care treatment while receiving additional OE/BOLD MRI and [18F]MISO PET scans at several timepoints during treatment. The ability of OE/BOLD MRI to map hypoxic tumour regions will be evaluated by assessing spatial and quantitative correlations with areas of hypoxic tumour identified via [18F]MISO PET imaging. Discussion: MANGO (Magnetic resonance imaging of hypoxia for radiation treatment guidance in glioblastoma multiforme) is a diagnostic/prognostic study investigating the role of imaging biomarkers of hypoxia in GBM management. The study will generate a large amount of longitudinal multimodal MRI and PET imaging data that could be used to unveil dynamic changes in tumour physiology that currently limit treatment efficacy, thereby providing a means to develop more effective and personalised treatments.
RESUMO
INTRODUCTION: Glioblastoma is the most common aggressive primary central nervous system cancer in adults characterised by uniformly poor survival. Despite maximal safe resection and postoperative radiotherapy with concurrent and adjuvant temozolomide-based chemotherapy, tumours inevitably recur. Imaging with O-(2-[18F]-fluoroethyl)-L-tyrosine (FET) positron emission tomography (PET) has the potential to impact adjuvant radiotherapy (RT) planning, distinguish between treatment-induced pseudoprogression versus tumour progression as well as prognostication. METHODS AND ANALYSIS: The FET-PET in Glioblastoma (FIG) study is a prospective, multicentre, non-randomised, phase II study across 10 Australian sites and will enrol up to 210 adults aged ≥18 years with newly diagnosed glioblastoma. FET-PET will be performed at up to three time points: (1) following initial surgery and prior to commencement of chemoradiation (FET-PET1); (2) 4 weeks following concurrent chemoradiation (FET-PET2); and (3) within 14 days of suspected clinical and/or radiological progression on MRI (performed at the time of clinical suspicion of tumour recurrence) (FET-PET3). The co-primary outcomes are: (1) to investigate how FET-PET versus standard MRI impacts RT volume delineation and (2) to determine the accuracy and management impact of FET-PET in distinguishing pseudoprogression from true tumour progression. The secondary outcomes are: (1) to investigate the relationships between FET-PET parameters (including dynamic uptake, tumour to background ratio, metabolic tumour volume) and progression-free survival and overall survival; (2) to assess the change in blood and tissue biomarkers determined by serum assay when comparing FET-PET data acquired prior to chemoradiation with other prognostic markers, looking at the relationships of FET-PET versus MRI-determined site/s of progressive disease post chemotherapy treatment with MRI and FET-PET imaging; and (3) to estimate the health economic impact of incorporating FET-PET into glioblastoma management and in the assessment of post-treatment pseudoprogression or recurrence/true progression. Exploratory outcomes include the correlation of multimodal imaging, blood and tumour biomarker analyses with patterns of failure and survival. ETHICS AND DISSEMINATION: The study protocol V.2.0 dated 20 November 2020 has been approved by a lead Human Research Ethics Committee (Austin Health, Victoria). Other clinical sites will provide oversight through local governance processes, including obtaining informed consent from suitable participants. The study will be conducted in accordance with the principles of the Declaration of Helsinki and Good Clinical Practice. Results of the FIG study (TROG 18.06) will be disseminated via relevant scientific and consumer forums and peer-reviewed publications. TRIAL REGISTRATION NUMBER: ANZCTR ACTRN12619001735145.
Assuntos
Neoplasias Encefálicas , Ficus , Glioblastoma , Adulto , Humanos , Adolescente , Glioblastoma/diagnóstico por imagem , Glioblastoma/terapia , Glioblastoma/patologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Tirosina , Estudos Prospectivos , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/terapia , Neoplasias Encefálicas/patologia , Recidiva Local de Neoplasia/diagnóstico por imagem , Austrália , Tomografia por Emissão de Pósitrons , Imageamento por Ressonância Magnética , Ensaios Clínicos Fase II como Assunto , Estudos Multicêntricos como AssuntoRESUMO
PURPOSE: Positron emission tomography (PET) imaging is increasingly used to confirm localization of (90)Y microspheres in the treatment of liver cancer. The aim of this work was to evaluate the quantification of (90)Y PET data on a current generation time-of-flight extended axial field-of-view PET∕CT camera. METHODS: The International Electrotechnical Commission (IEC) body phantom was used to image six spheres of varying diameters containing a high concentration of (90)Y solution in a lower concentration background. Multiple PET studies were acquired of the phantom over a number of days during decay. The effect of reconstruction parameters in OSEM was evaluated both qualitatively and quantitatively. Expected values of total phantom activity, hot-sphere, and background concentration were compared to measured values from the reconstructed data as well as misplaced events in a cold insert. The partial volume effect was measured and the effects of time-of-flight during reconstruction on hot contrast recovery and background variability were evaluated according to NEMA-NU2-2007 protocol, and compared to that for (18)F. The method was applied to a patient study following radioembolization to estimate actual implanted radioactivity. RESULTS: Increasing the number of OSEM iterations visually deteriorated image data and resulted in a larger overall difference of hot concentration measures when considering both count high and count poor data. The average difference between measured and true total activity and background concentration was found to be +5% and +5%, respectively. Measured hot-sphere concentration was linear across all datasets, and while estimated to be within error of expected values, was consistently underestimated by an average of 23%, 12%, and 8%, when using a CT-derived, 50% threshold-derived, and 70% threshold-derived volume of interest, respectively. Partial volume effects were evident in all but the largest sphere, following an expected relationship between object size and recovery coefficient, inferior to that of (18)F. Time-of-flight improved contrast of hot-spheres but resulted in a deterioration of background variability, following a similar trend to that seen with (18)F. The patient data estimated a total implanted activity of 1643 MBq, compared to the intended dose of 1780 MBq, with a difference most likely due to residual and error in the initial dose calibration. CONCLUSIONS: Quantitative (90)Y PET with a state-of-the-art PET∕CT scanner with time-of-flight and standard corrections for photon interactions demonstrates consistent and acceptable measures of total activity and radionuclide concentration across a range of realistic count statistics. The method is suitable for measuring the radioactivity delivered at the time of (90)Y therapy with the potential for absorbed dose calculation.
Assuntos
Processamento de Imagem Assistida por Computador/métodos , Tomografia por Emissão de Pósitrons/métodos , Calibragem , Humanos , Software , Tomografia Computadorizada por Raios X , Radioisótopos de ÍtrioAssuntos
Fluordesoxiglucose F18/farmacologia , Arterite de Células Gigantes , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Artérias Temporais/diagnóstico por imagem , Artéria Vertebral/diagnóstico por imagem , Transtornos da Visão , Idoso , Técnicas de Diagnóstico Oftalmológico , Feminino , Arterite de Células Gigantes/complicações , Arterite de Células Gigantes/diagnóstico , Arterite de Células Gigantes/fisiopatologia , Humanos , Compostos Radiofarmacêuticos/farmacologia , Reprodutibilidade dos Testes , Artérias Temporais/patologia , Artéria Vertebral/patologia , Transtornos da Visão/diagnóstico , Transtornos da Visão/etiologiaRESUMO
The objective of the study is to retrospectively measure patient radiation dose resulting from whole body X-ray CT and FDG PET studies using a low-dose protocol performed on the Siemens Biograph mCT scanner. A total of 483 patient studies were reviewed. For each, the CT dose-length product was used to estimate radiation dose to the patient as a result of the whole body X-ray CT component of the PET/CT study. The net injected FDG dose was used to calculate the whole body effective dose based on ICRP recommendations. Dose calculations were also modified to take into account individual patient weight. The total effective dose received by each patient was taken as the sum of the PET and CT components of the study. The mean effective dose from the CT component of the diagnostic study was found to be 8.2 mSv (3.4-23.4 mSv), for a CT protocol of 120 kV(p) and effective tube current-time product of 80 mAs with automatic exposure control. For an average injected FDG activity of 304 MBq the mean PET effective dose was found to be 6.3 mSv when using the ICRP standard models, or 6.0 mSv when scaling effective dose to individual patient weight or patient blood volume. The average total effective dose across the entire patient cohort for a combined PET/CT study was found to be ~14.5 mSv (9.6-29.8 mSv). Low-dose protocols for whole-body PET/CT scanning result in an effective radiation dose to the patient of approximately 14.5 mSv. Additional reductions through the use of iterative CT reconstruction and optimized low-dose FDG protocols could see total effective doses for whole-body PET/CT fall to below 10 mSv.
Assuntos
Peso Corporal , Fluordesoxiglucose F18 , Imagem Multimodal/métodos , Tomografia por Emissão de Pósitrons , Doses de Radiação , Tomografia Computadorizada por Raios X , Imagem Corporal Total/métodos , Adulto , Estudos de Coortes , Feminino , Humanos , Masculino , Radiometria , Estudos RetrospectivosRESUMO
BACKGROUND: The prediction of response is one of the major challenges in radiation-based therapies. Although the selection of accurate linear-quadratic model parameters is essential for the estimation of radiation response and treatment outcome, there is a limited knowledge about these radiobiological parameters for liver tumours using radionuclide treatments. METHODS: The "clinical radiobiological" parameters ([Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text]) for twenty-five patients were derived using the generalised linear-quadratic model, the diagnostic ([18F] FDG PET/CT) and therapeutic ([90Y]-SIR-Spheres PET/CT) images to compute the biological effective dose and tumour control probability (TCP) for each patient. RESULTS: It was estimated that the values for [Formula: see text] and [Formula: see text] parameters range in ≈ 0.001-1 Gy-1 and ≈ 1-49 Gy, respectively. We have demonstrated that the time factors, [Formula: see text], [Formula: see text] and [Formula: see text] are the key parameters when evaluating liver malignancy lesional response to [90Y]SIR-Spheres treatment. Patients with cholangiocarcinoma have been shown to have the longest average [Formula: see text] (≈ 236 ± 67 d), highest TCP (≈ 53 ± 17%) and total liver lesion glycolysis response ([Formula: see text] ≈ 64%), while patients with metastatic colorectal cancer tumours have the shortest average [Formula: see text] (≈ 129 ± 19 d), lowest TCP (≈ 28 ± 13%) and [Formula: see text] ≈ 8%, respectively. CONCLUSIONS: Tumours with shorter [Formula: see text] have shown a shorter [Formula: see text] and thus poorer TCP and [Formula: see text]. Therefore, these results suggest for such tumours the [90Y]SIR-Spheres will be only effective at higher initial dose rate (e.g. > 50 Gy/day).
RESUMO
This report is of an unusual case of radioactive contamination of a gamma camera after scanning two individuals who had been treated 3 days prior with ablative doses of radioiodine (131I) for thyroid cancer. A combination of observed half-life and pulse-height spectroscopy were employed to identify the radio-contaminant. The source of the contamination was eventually found to be a single human hair, presumably contaminated by the individual sucking her hair while waiting for the scan to start. This case demonstrates that hair can be contaminated by saliva and potentially other bodily fluids in the post-ablation setting and that using physical characteristics, in this case the observed half-life and pulse-height spectroscopy, can be useful in identifying the radio-contaminant.