ABSTRACT
OBJECTIVE: The effects of hormonal therapy, estrogen-based hormone replacement therapy (HRT), and anti-tumor hormone therapy, such as tamoxifen, on the physiological uptake of the endometrium on 2-deoxy-2[18F]fluoro-D-glucose ([18F]F-FDG) positron emission tomography (PET) in postmenopausal women have not been determined. We explored the effect of hormone therapy, particularly HRT, on physiological uptake in the endometrium of postmenopausal women. MATERIALS AND METHODS: Postmenopausal women receiving hormone therapy who underwent cancer screening using PET/computed tomography (CT) between June 2016 and April 2023 were included in the hormone therapy group (n = 21). Postmenopausal women with no history of hormone therapy were included in the control group (n = 49). First, the physiological endometrial uptake at menopausal age and at least 1 year thereafter was compared quantitatively (SUVmax) and qualitatively (4-point scale) in the control group, to assess when the endometrium ceased to show significant physiological [18F]F-FDG uptake after menopause. Endometrial uptake was compared between the hormone therapy and control groups. The association between HRT duration (months) and endometrial uptake (SUVmax) was evaluated. Endometrial thickness, measured using transvaginal ultrasonography, was also compared between the two groups. RESULTS: Endometrial uptake was significantly reduced both qualitatively and quantitatively (P < 0.05) at least 1 year after menopause in control patients, by which time most women (89.8%) no longer had significant endometrial uptake. The hormone therapy group (n = 21) showed higher FDG uptake in the endometrium compared to the control group (median SUVmax: 2.3 vs 1.9, P = 0.0011), as well as a higher visual score (P < 0.0001). HRT duration did not correlate with endometrial uptake (P = 0.097). Endometrial thickness in the hormone therapy group was significantly thicker than in the control group (median: 3.9 mm vs 1.8 mm, P = 0.002). CONCLUSION: Hormone therapy may affect physiological uptake in the endometrium in postmenopausal women.
ABSTRACT
With the aging of the population, malignancies are becoming common complications in patients with rheumatoid arthritis (RA), particularly in elderly patients. Such malignancies often interfere with RA treatment. Among several therapeutic agents, immune checkpoint inhibitors (ICIs) which antagonize immunological brakes on T lymphocytes have emerged as a promising treatment option for a variety of malignancies. In parallel, evidence has accumulated that ICIs are associated with numerous immune-related adverse events (irAEs), such as hypophysitis, myocarditis, pneumonitis, and colitis. Moreover, ICIs not only exacerbate pre-existing autoimmune diseases, but also cause de novo rheumatic disease-like symptoms, such as arthritis, myositis, and vasculitis, which are currently termed rheumatic irAEs. Rheumatic irAEs differ from classical rheumatic diseases in multiple aspects, and treatment should be individualized based on the severity. Close collaboration with oncologists is critical for preventing irreversible organ damage. This review summarizes the current evidence regarding the mechanisms and management of rheumatic irAEs with focus on arthritis, myositis, and vasculitis. Based on these findings, potential therapeutic strategies against rheumatic irAEs are discussed.
Subject(s)
Arthritis, Rheumatoid , Myositis , Neoplasms , Rheumatic Diseases , Vasculitis , Humans , Aged , Immune Checkpoint Inhibitors/adverse effects , Rheumatic Diseases/therapy , Arthritis, Rheumatoid/drug therapy , Arthritis, Rheumatoid/complications , Neoplasms/drug therapy , Neoplasms/complications , Myositis/chemically induced , Myositis/drug therapy , Vasculitis/drug therapyABSTRACT
Rationale: There is a growing need to accurately estimate the prognosis of idiopathic pulmonary fibrosis (IPF) in clinical practice, given the development of effective drugs for treating IPF. Objectives: To develop artificial intelligence-based image analysis software to detect parenchymal and airway abnormalities on computed tomographic (CT) imaging of the chest and to explore their prognostic importance in patients with IPF. Methods: A novel artificial intelligence-based quantitative CT image analysis software (AIQCT) was developed by applying 304 high-resolution CT (HRCT) scans from patients with diffuse lung diseases as the training set. AIQCT automatically categorized and quantified 10 types of parenchymal patterns as well as airways, expressing the volumes as percentages of the total lung volume. To validate the software, the area percentages of each lesion quantified by AIQCT were compared with those of the visual scores using 30 plain high-resolution CT images with lung diseases. In addition, three-dimensional analysis for similarity with ground truth was performed using HRCT images from 10 patients with IPF. AIQCT was then applied to 120 patients with IPF who underwent HRCT scanning of the chest at our institute. Associations between the measured volumes and survival were analyzed. Results: The correlations between AIQCT and the visual scores were moderate to strong (correlation coefficient 0.44-0.95) depending on the parenchymal pattern. The Dice indices for similarity between AIQCT data and ground truth were 0.67, 0.76, and 0.64 for reticulation, honeycombing, and bronchi, respectively. During a median follow-up period of 2,184 days, 66 patients died, and 1 underwent lung transplantation. In multivariable Cox regression analysis, bronchial volumes (adjusted hazard ratio [HR], 1.33; 95% confidence interval [CI], 1.16-1.53) and normal lung volumes (adjusted HR, 0.97; 95% CI, 0.94-0.99) were independently associated with survival after adjusting for the gender-age-lung physiology stage of IPF. Conclusions: Our newly developed artificial intelligence-based image analysis software successfully quantified parenchymal lesions and airway volumes. Bronchial and normal lung volumes on HRCT imaging of the chest may provide additional prognostic information on the gender-age-lung physiology stage of IPF.
Subject(s)
Idiopathic Pulmonary Fibrosis , Artificial Intelligence , Humans , Idiopathic Pulmonary Fibrosis/diagnostic imaging , Idiopathic Pulmonary Fibrosis/pathology , Lung/diagnostic imaging , Lung/pathology , Retrospective Studies , Technology , Tomography, X-Ray Computed/methodsABSTRACT
PURPOSE: Immunotherapy is a promising approach for many oncological malignancies, including glioblastoma, however, there are currently no available tools or biomarkers to accurately assess whole-body immune responses in patients with glioblastoma treated with immunotherapy. Here, the utility of OX40, a costimulatory molecule mainly expressed on activated effector T cells known to play an important role in eliminating cancer cells, was evaluated as a PET imaging biomarker to quantify and track response to immunotherapy. EXPERIMENTAL DESIGN: A subcutaneous vaccination approach of CpG oligodeoxynucleotide, OX40 mAb, and tumor lysate at a remote site in a murine orthotopic glioma model was developed to induce activation of T cells distantly while monitoring their distribution in stimulated lymphoid organs with respect to observed therapeutic effects. To detect OX40-positive T cells, we utilized our in-house-developed 89Zr-DFO-OX40 mAb and in vivo PET/CT imaging. RESULTS: ImmunoPET with 89Zr-DFO-OX40 mAb revealed strong OX40-positive responses with high specificity, not only in the nearest lymph node from vaccinated area (mean, 20.8%ID/cc) but also in the spleen (16.7%ID/cc) and the tumor draining lymph node (11.4%ID/cc). When the tumor was small (<106 p/sec/cm2/sr in bioluminescence imaging), a high number of responders and percentage shrinkage in tumor signal was indicated after only a single cycle of vaccination. CONCLUSIONS: The results highlight the promise of clinically translating cancer vaccination as a potential glioma therapy, as well as the benefits of monitoring efficacy of these treatments using immunoPET imaging of T-cell activation.
Subject(s)
Glioblastoma , Animals , Cell Line, Tumor , Glioblastoma/diagnostic imaging , Glioblastoma/therapy , Humans , Mice , Positron Emission Tomography Computed Tomography/methods , Positron-Emission Tomography , T-Lymphocytes/pathologyABSTRACT
Diagnosis of organ transplant rejection relies upon biopsy approaches to confirm alloreactive T cell infiltration in the graft. Immune molecular monitoring is under investigation to screen for rejection, though these techniques have suffered from low specificity and lack of spatial information. ImmunoPET utilizing antibodies conjugated to radioisotopes has the potential to improve early and accurate detection of graft rejection. ImmunoPET is capable of noninvasively visualizing the dynamic distribution of cells expressing specific immune markers in the entire body over time. In this work, we identify and characterize OX40 as a surrogate biomarker for alloreactive T cells in organ transplant rejection and monitor its expression by utilizing immunoPET. In a dual murine heart transplant model that has both syngeneic and allogeneic hearts engrafted in bilateral ear pinna on the recipients, OX40 immunoPET clearly depicted alloreactive T cells in the allograft and draining lymph node that were not observed in their respective isograft counterparts. OX40 immunoPET signals also reflected the subject's immunosuppression level with tacrolimus in this study. OX40 immunoPET is a promising approach that may bridge molecular monitoring and morphological assessment for improved transplant rejection diagnosis.
Subject(s)
Graft Rejection , Heart Transplantation/adverse effects , Monitoring, Immunologic/methods , OX40 Ligand , Positron-Emission Tomography/methods , T-Lymphocytes/immunology , Animals , Antigens, Differentiation/analysis , Biomarkers/analysis , Early Diagnosis , Gene Expression Profiling/methods , Graft Rejection/diagnosis , Graft Rejection/immunology , Humans , Mass Screening/methods , Mice , OX40 Ligand/analysis , OX40 Ligand/immunology , Radioimmunoassay/methodsABSTRACT
PURPOSE: We investigated the ability of baseline 2-deoxy-2-[18F]fluoro-D-glucose PET/CT parameters, acquired before the start of immunotherapy, to predict development of hyperprogressive disease (HPD) in melanoma patients. We also evaluated the diagnostic performances of ratios of baseline and first restaging PET/CT parameters to diagnose HPD without information of the tumor growth kinetic ratio (TGKR) that requires pre-baseline imaging before baseline imaging (3 timepoint imaging). PROCEDURES: Seventy-six patients who underwent PET/CT before and approximately 3 months following initiation of immunotherapy were included. PET/CT parameters, including metabolic tumor volume (MTV) for all melanoma lesions and total measured tumor burden (TMTB) based on irRECIST, were measured from baseline PET/CT (MTVbase and TMTBbase) and first restaging PET/CT (MTVpost and TMTBpost). The ratios of MTV (MTVpost/MTVbase, MTVr) and TMTB (TMTBpost/TMTBbase, TMTBr) were calculated. RESULTS: MTVbase of HPD patients (n = 9, TGKR ≥ 2) was larger than that of non-HPD (n = 67, TGKR < 2) patients (P < 0.05), and HPD patients demonstrated shorter median overall survival (7 vs. more than 60 months, P < 0.05). The area under the curve (AUC) of MTVbase (≥ 155.5 ml) to predict the risk of HPD was 0.703, with a sensitivity of 66.7 % and specificity of 81.2 %. The AUCs of MTVr (≥ 1.25) and TMTBr (≥ 1.27) to diagnose HPD without information of TGKR were 0.875 and 0.977 with both sensitivities of 100 %, and specificities of 79 % and 83.9 %, respectively. CONCLUSIONS: Patients at high risk of developing HPD could not be accurately identified based on baseline PET/CT parameters. The ratios of baseline and first restaging PET/CT parameters may be helpful to diagnose HPD, when patients do not undergo pre-baseline imaging.
Subject(s)
Disease Progression , Fluorodeoxyglucose F18/chemistry , Immunotherapy , Melanoma/diagnostic imaging , Melanoma/therapy , Positron Emission Tomography Computed Tomography , Skin Neoplasms/diagnostic imaging , Skin Neoplasms/therapy , Aged , Female , Humans , Kaplan-Meier Estimate , Kinetics , Male , Melanoma/diagnosis , Middle Aged , ROC Curve , Skin Neoplasms/diagnosis , Tumor BurdenABSTRACT
Despite the relative ease of locating organs in the human body, automated organ segmentation has been hindered by the scarcity of labeled training data. Due to the tedium of labeling organ boundaries, most datasets are limited to either a small number of cases or a single organ. Furthermore, many are restricted to specific imaging conditions unrepresentative of clinical practice. To address this need, we developed a diverse dataset of 140 CT scans containing six organ classes: liver, lungs, bladder, kidney, bones and brain. For the lungs and bones, we expedited annotation using unsupervised morphological segmentation algorithms, which were accelerated by 3D Fourier transforms. Demonstrating the utility of the data, we trained a deep neural network which requires only 4.3 s to simultaneously segment all the organs in a case. We also show how to efficiently augment the data to improve model generalization, providing a GPU library for doing so. We hope this dataset and code, available through TCIA, will be useful for training and evaluating organ segmentation models.
Subject(s)
Image Processing, Computer-Assisted/methods , Neural Networks, Computer , Tomography, X-Ray Computed , Algorithms , Bone and Bones/diagnostic imaging , Brain/diagnostic imaging , Fourier Analysis , Humans , Imaging, Three-Dimensional/methods , Kidney/diagnostic imaging , Liver/diagnostic imaging , Lung/diagnostic imaging , Urinary Bladder/diagnostic imagingABSTRACT
Graft-versus-host disease (GvHD) is a major complication of allogeneic hematopoietic cell transplantation (HCT), mediated primarily by donor T cells that become activated and attack host tissues. Noninvasive strategies detecting T-cell activation would allow for early diagnosis and possibly more effective management of HCT recipients. PET imaging is a sensitive and clinically relevant modality ideal for GvHD diagnosis, and there is a strong rationale for the use of PET tracers that can monitor T-cell activation and expansion with high specificity. The TNF receptor superfamily member OX40 (CD134) is a cell surface marker that is highly specific for activated T cells, is upregulated during GvHD, and mediates disease pathogenesis. We recently reported the development of an antibody-based activated T-cell imaging agent targeting OX40. In the present study, we visualize the dynamics of OX40 expression in an MHC-mismatch mouse model of acute GvHD using OX40-immunoPET. This approach enabled visualization of T-cell activation at early stages of disease, prior to overt clinical symptoms with high sensitivity and specificity. This study highlights the potential utility of the OX40 PET imaging as a new strategy for GvHD diagnosis and therapy monitoring. SIGNIFICANCE: OX40-immunoPET imaging is a promising noninvasive strategy for early detection of GvHD, capable of detecting signs of GvHD pathology even prior to the development of overt clinical symptoms.
Subject(s)
Graft vs Host Disease/immunology , Positron Emission Tomography Computed Tomography/methods , Radiopharmaceuticals/pharmacology , Receptors, OX40/analysis , T-Lymphocytes , Animals , Antibodies, Monoclonal/pharmacology , Copper Radioisotopes/pharmacology , Lymphocyte Activation , Mice , Receptors, OX40/metabolism , Tissue DistributionABSTRACT
OBJECTIVE: To investigate the clinical and radiological features of immune checkpoint inhibitor-related pneumonitis (ICI-P), a rare but serious pulmonary complication of cancer immunotherapy and to evaluate key differences between lung cancer (LC) and non-LC patients. METHODS: 247 patients (LC, n = 151) treated with ICI for malignancies were retrospectively screened in a single institute. The number of patients, history of other immune-related adverse events (irAE), the onset, serum KL-6 levels, and chest CT features (types of pneumonitis, symmetry, laterality, location) were recorded for the ICI-P population and compared for LC and non-LC groups. RESULTS: ICI-P was identified in 26 patients in total (LC, n = 19; non-LC, n = 7). The incidence of other irAE was significantly higher in ICI-P group (63%) compared with patients without ICI-P (34%) (p = 0.0056). An earlier onset of ICI-P was recorded in LC (78 days) compared to non-LC patients (186 days) (p = 0.0034). Serum KL-6 was significantly elevated only in the non-LC group when ICI-P was noticed (p = 0.029). Major CT findings of ICI-P, irrespective of primary disease, were organizing pneumonia pattern and ground glass opacities. LC patients commonly exhibited consolidation and traction bronchiectasis and were prone to asymmetrical shadows (p < 0.001). Non-LC patients were more likely to exhibit symmetrical infiltrations. A small fraction of both groups experienced relapse or moving patterns of ICI-P. CONCLUSION: ICI-P patients more often experienced other irAE prior to the development of ICI-P. The characteristics of ICI-P can differ in terms of the onset, KL-6 reliability, and chest CT findings between LC and non-LC patients. ADVANCES IN KNOWLEDGE: In ICI-P patients, a history of other irAE can be more frequently observed. Differences in disease onset and radiological patterns between LC and non-LC patients might be helpful to make a diagnosis of ICI-P; however, longitudinal observation of chest CT scans is advised to observe the pneumonitis activity irrespective of cancer types.
Subject(s)
Antineoplastic Agents, Immunological/adverse effects , Neoplasms/therapy , Pneumonia/chemically induced , Pneumonia/diagnostic imaging , Aged , Aged, 80 and over , Antibodies, Monoclonal, Humanized/adverse effects , Antibodies, Monoclonal, Humanized/therapeutic use , Antineoplastic Agents, Immunological/therapeutic use , Bronchiectasis/diagnostic imaging , CTLA-4 Antigen/antagonists & inhibitors , Cryptogenic Organizing Pneumonia/chemically induced , Cryptogenic Organizing Pneumonia/diagnostic imaging , Female , Humans , Lung Neoplasms/therapy , Male , Middle Aged , Nivolumab/adverse effects , Nivolumab/therapeutic use , Polysaccharides, Bacterial/blood , Programmed Cell Death 1 Receptor/antagonists & inhibitors , Radiation Pneumonitis/diagnostic imaging , Retrospective Studies , Tomography, X-Ray ComputedABSTRACT
PURPOSE: The purpose of this study was to investigate the prognostic value of whole-body metabolic tumor volume (MTV) and other metabolic tumor parameters, obtained from baseline and first restaging 18F-FDG PET/CT scans in melanoma patients treated with immune checkpoint inhibitors (ICIs). METHODS: Eighty-five consecutive melanoma patients (M, 57; F, 28) treated with ICIs who underwent PET/CT scans before and approximately 3 months after the start of immunotherapy were retrospectively enrolled. Metabolic tumor parameters including MTV for all melanoma lesions were measured on each scan. A Cox proportional hazards model was used for univariate and multivariate analyses of metabolic parameters combined with known clinical prognostic factors associated with overall survival (OS). Kaplan-Meier curves for patients dichotomized based on median values of imaging parameters were generated. RESULTS: The median OS time in all patients was 45 months (95% CI 24-45 months). Univariate analysis demonstrated that MTV obtained from first restaging PET/CT scans (MTVpost) was the strongest prognostic factor for OS among PET/CT parameters (P < 0.0001). The median OS in patients with high MTVpost (≥ 23.44) was 16 months (95% CI 12-32 months) as compared with more than 60 months in patients with low MTVpost (< 23.44) (P = 0.0003). A multivariate model including PET/CT parameters and known clinical prognostic factors revealed that MTVpost and the presence of central nervous system lesions were independent prognostic factors for OS (P = 0.0004, 0.0167, respectively). One pseudoprogression case (1.2%) was seen in this population and classified into the high MTVpost group. CONCLUSION: Whole-body metabolic tumor volume from PET scan acquired approximately 3 months following initiation of immunotherapy (MTVpost) is a strong prognostic indicator of OS in melanoma patients. Although the possibility of pseudoprogression must be considered whenever evaluating first restaging PET imaging, it only occurred in 1 patient in our cohort.
Subject(s)
Melanoma , Positron Emission Tomography Computed Tomography , Fluorodeoxyglucose F18 , Humans , Immunotherapy , Melanoma/diagnostic imaging , Melanoma/drug therapy , Prognosis , Retrospective Studies , Tumor BurdenABSTRACT
Immunotherapy is innovating clinical cancer management. Nevertheless, only a small fraction of patient's benefit from current immunotherapies. To improve clinical management of cancer immunotherapy, it is critical to develop strategies for response monitoring and prediction. In this study, we describe inducible T-cell costimulator (ICOS) as a conserved mediator of immune response across multiple therapy strategies. ICOS expression was evaluated by flow cytometry, 89Zr-DFO-ICOS mAb PET/CT imaging was performed on Lewis lung cancer models treated with different immunotherapy strategies, and the change in tumor volume was used as a read-out for therapeutic response. ImmunoPET imaging of ICOS enabled sensitive and specific detection of activated T cells and early benchmarking of immune response. A STING (stimulator of interferon genes) agonist was identified as a promising therapeutic approach in this manner. The STING agonist generated significantly stronger immune responses as measured by ICOS ImmunoPET and delayed tumor growth compared with programmed death-1 checkpoint blockade. More importantly, ICOS ImmunoPET enabled early and robust prediction of therapeutic response across multiple treatment regimens. These data show that ICOS is an indicator of T-cell-mediated immune response and suggests ICOS ImmunoPET as a promising strategy for monitoring, comparing, and predicting immunotherapy success in cancer. SIGNIFICANCE: ICOS ImmunoPET is a promising strategy to noninvasively predict and monitor immunotherapy response.See related commentary by Choyke, p. 2975.
Subject(s)
Molecular Imaging , Neoplasms , Humans , Immunotherapy , Inducible T-Cell Co-Stimulator Protein , Neoplasms/therapy , Positron Emission Tomography Computed Tomography , T-LymphocytesABSTRACT
PET using radiolabeled prostate-specific membrane antigen (PSMA) is now being more widely adopted as a valuable tool to evaluate patients with prostate cancer (PC). Recently, 3 different criteria for interpretation of PSMA PET were published: the European Association of Nuclear Medicine (EANM) criteria, the Prostate Cancer Molecular Imaging Standardized Evaluation criteria, and the PSMA Reporting and Data System. We compared these 3 criteria in terms of interreader, intrareader, and intercriteria agreement. Methods: Data from 104 patients prospectively enrolled in research protocols at our institution were retrospectively reviewed. The cohort consisted of 2 groups: 47 patients (mean age, 64.2 y old) who underwent Glu-NH-CO-NH-Lys-(Ahx)-[68Ga(HBED-CC)] (68Ga-PSMA11) PET/MRI for initial staging of biopsy-proven intermediate- or high-risk PC, and 57 patients (mean age, 70.5 y old) who underwent 68Ga-PSMA11 PET/CT because of biochemically recurrent PC. Three nuclear medicine physicians independently evaluated all 68Ga-PSMA11 PET/MRI and PET/CT studies according to the 3 interpretation criteria. Two of them reevaluated all studies 6 mo later in the same manner and masked to the initial reading. The Gwet agreement coefficient was calculated to evaluate interreader, intrareader, and intercriteria agreement based on the following sites: local lesion (primary tumor or prostate bed after radical prostatectomy), lymph node metastases, and other metastases. Results: In the PET/MRI group, interreader, intrareader, and intercriteria agreement ranged from substantial to almost perfect for any site according to all 3 criteria. In the PET/CT group, interreader agreement ranged from substantial to almost perfect except for judgment of distant metastases based on the PSMA Reporting and Data System (Gwet agreement coefficient, 0.57; moderate agreement), in which the most frequent cause of disagreement was lung nodules. Intrareader agreement ranged from substantial to almost perfect for any site according to all 3 criteria. Intercriteria agreement for each site was also substantial to almost perfect. Conclusion: Although the 3 published criteria have good interreader and intrareader reproducibility in evaluating 68Ga-PSMA11 PET, there are some factors causing interreader disagreement. Further work is needed to address this issue.
Subject(s)
Edetic Acid/analogs & derivatives , Image Interpretation, Computer-Assisted , Oligopeptides , Positron-Emission Tomography , Aged , Gallium Isotopes , Gallium Radioisotopes , Humans , Magnetic Resonance Imaging , Male , Multimodal Imaging , Observer Variation , Prostatic Neoplasms/diagnostic imagingABSTRACT
The high-background glucose metabolism of normal gray matter on [18F]-fluoro-2-D-deoxyglucose (FDG) positron emission tomography (PET) of the brain results in a low signal-to-background ratio, potentially increasing the possibility of missing important findings in patients with intracranial malignancies. To explore the strategy of using a deep learning classifier to aid in distinguishing normal versus abnormal findings on PET brain images, this study evaluated the performance of a two-dimensional convolutional neural network (2D-CNN) to classify FDG PET brain scans as normal (N) or abnormal (A). METHODS: Two hundred eighty-nine brain FDG-PET scans (N; n = 150, A; n = 139) resulting in a total of 68,260 images were included. Nine individual 2D-CNN models with three different window settings for axial, coronal, and sagittal axes were trained and validated. The performance of these individual and ensemble models was evaluated and compared using a test dataset. Odds ratio, Akaike's information criterion (AIC), and area under curve (AUC) on receiver-operative-characteristic curve, accuracy, and standard deviation (SD) were calculated. RESULTS: An optimal window setting to classify normal and abnormal scans was different for each axis of the individual models. An ensembled model using different axes with an optimized window setting (window-triad) showed better performance than ensembled models using the same axis and different windows settings (axis-triad). Increase in odds ratio and decrease in SD were observed in both axis-triad and window-triad models compared with individual models, whereas improvements of AUC and AIC were seen in window-triad models. An overall model averaging the probabilities of all individual models showed the best accuracy of 82.0%. CONCLUSIONS: Data ensemble using different window settings and axes was effective to improve 2D-CNN performance parameters for the classification of brain FDG-PET scans. If prospectively validated with a larger cohort of patients, similar models could provide decision support in a clinical setting.
Subject(s)
Brain , Brain/diagnostic imaging , Brain Neoplasms/diagnostic imaging , Fluorodeoxyglucose F18 , Humans , Neural Networks, Computer , Positron-Emission TomographyABSTRACT
PURPOSE: To evaluate the prognostic value of volumetric parameters calculated from 68Ga-1,4,7,10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid (DOTA)-Thr3-octreotate (68Ga-DOTATATE) positron emission tomography/computed tomography (PET/CT) in patients with well-differentiated neuroendocrine tumor (WD-NET). METHODS: Ninety-two patients (44 men and 48 women, mean age of 59.5-year-old) with pathologically confirmed WD-NET (grades 1 or 2) were enrolled in a prospective expanded access protocol. Selected data was analyzed retrospectively for this project. Maximum standardized uptake value (SUVmax) in the lesion with the highest 68Ga-DOTATATE uptake was measured and recorded for each patient. In addition, two volumetric parameters, namely, somatostatin receptor expressing tumor volume (SRETV) and total lesion somatostatin receptor expression (TLSRE), were calculated in each 68Ga-DOTATATE-avid lesion. SRETV was defined as tumor volume with higher 68Ga-DOTATATE uptake than the 50% of SUVmax within the volume of interest (VOI) for each lesion. TLSRE was calculated by multiplying SRETV and mean SUV within the same VOI. Thereafter, the sum of SRETV (ΣSRETV) and TLSRE (ΣTLSRE) for all detected lesions per patient were calculated. Progression-free survival (PFS) was set as primary endpoint. Kaplan-Meier survival analysis, log-rank test, and Cox's proportional hazard model were used for statistical analysis. RESULTS: Univariate analyses revealed significant difference of PFS for WHO tumor grade and ΣSRETV (P < 0.05), while there were no significant differences in age, sex, SUVmax, and ΣTLSRE (P > 0.05). Multivariate analysis identified WHO tumor grade and ΣSRETV as independent predictors of PFS. CONCLUSION: ΣSRETV calculated from 68Ga-DOTATATE PET/CT may have prognostic value of PFS in WD-NET patients.
Subject(s)
Neuroendocrine Tumors/diagnostic imaging , Organometallic Compounds/chemistry , Positron Emission Tomography Computed Tomography , Receptors, Somatostatin/analysis , Adult , Aged , Aged, 80 and over , Disease Progression , Disease-Free Survival , Female , Humans , Image Processing, Computer-Assisted , Kaplan-Meier Estimate , Liver Neoplasms/diagnostic imaging , Liver Neoplasms/secondary , Male , Middle Aged , Multivariate Analysis , Neoplasm Metastasis , Prognosis , Progression-Free Survival , Proportional Hazards Models , Prospective Studies , Retrospective StudiesABSTRACT
PURPOSE: To investigate whether the evaluation of tumors, lymphoid cell-rich organs, and immune-related adverse events (IRAE) with F-FDG PET/CT can predict the efficacy and outcome of immunotherapy. METHODS: Forty patients who underwent F-FDG-PET/CT scans before and after therapy with immune checkpoint inhibitors from December 2013 to December 2016 were retrospectively enrolled (malignant melanoma, n = 21; malignant lymphoma, n = 11; renal cell carcinoma, n = 8). SUVmax of the baseline and first restaging scans were evaluated in tumors, spleen, bone marrow, thyroid and pituitary glands, and were correlated to best overall response in the first year after therapy; IRAE-affected areas were also evaluated. RESULTS: Interval change between the baseline and first restaging scans showed that patients with a clinical benefit had a significant decrease in tumor parameters (P < 0.001). All patients with an increase of SUVmax in the thyroid of more than 1.5 (n = 5) on the first restaging scan had a complete response (CR) in 1 year. Patients with CR within 1 year (n = 22) were significantly associated with a favorable long-term outcome (P = 0.002). Nine patients with IRAE findings had CR at final evaluation. Among IRAE, thyroiditis was seen significantly earlier than arthritis (P = 0.040). CONCLUSIONS: The decrease of tumor parameters at early time-point PET scans was seen in patients with immunotherapy who had clinical benefit within 1 year. PET-detectable IRAE was useful for prediction of a favorable outcome. Early development of thyroiditis may particularly represent an early response indicator to immunotherapy.
Subject(s)
Fluorodeoxyglucose F18 , Immunotherapy/adverse effects , Lymphocytes/immunology , Neoplasms/immunology , Neoplasms/therapy , Positron Emission Tomography Computed Tomography , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Neoplasms/diagnostic imaging , Retrospective Studies , Treatment Outcome , Young AdultSubject(s)
Antibodies, Monoclonal, Humanized/adverse effects , Antineoplastic Agents, Immunological/adverse effects , Arthritis/chemically induced , Melanoma/drug therapy , Programmed Cell Death 1 Receptor/drug effects , Aged , Antibodies, Monoclonal, Humanized/therapeutic use , Antineoplastic Agents, Immunological/therapeutic use , Arthritis/diagnostic imaging , Arthritis/physiopathology , Fluorodeoxyglucose F18 , Humans , Joints/diagnostic imaging , Joints/drug effects , Joints/physiopathology , Male , Positron-Emission Tomography , Prednisolone/therapeutic use , Whole Body ImagingABSTRACT
BACKGROUND: Perfusion-related intravoxel incoherent motion (IVIM) and non-Gaussian diffusion magnetic resonance (MR) parameters are becoming important biomarkers for differentiating malignant from benign tumors without contrast agents. However, diffusion-time dependence has rarely been investigated in tumors. PURPOSE: To investigate the relationship between diffusion time and diffusion parameters in breast cancer and hepatocellular carcinoma xenograft mouse models. MATERIAL AND METHODS: Diffusion-weighted MR images (DWI) were obtained on a 7-T magnetic resonance imaging (MRI) scanner at two different diffusion times (9.6 ms and 27.6 ms) in human breast cancer (MDA-MB-231) and hepatocellular carcinoma (HepG2 and PLC/PRF/5) xenograft mouse models. Perfusion-related IVIM (fIVIM and D*) and non-Gaussian diffusion (ADC0 and K) parameters were estimated. Parametric maps of diffusion changes with the diffusion times were generated using a synthetic apparent diffusion coefficient (sADC) obtained from b = 438 and 2584 s/mm2. RESULTS: ADC0 values significantly decreased when diffusion times were changed from 9.6 ms to 27.6 ms in MDA-MB-231, HepG2, and PLC/PRF/5 groups (P = 0.0163, 0.0351, and 0.0170, respectively). K values significantly increased in MDA-MB-231 and HepG2 groups (P < 0.0003 and = 0.0007, respectively); however, no significant difference was detected in the PLC/PRF/5 group. fIVIM values increased, although not significantly (P = 0.164-0.748). The maps of sADC changes showed that diffusion changes with the diffusion time were not homogeneous across tumor tissues. CONCLUSION: Diffusion MR parameters in both breast cancer and HCC xenograft models were found to be diffusion time-dependent. Our results show that diffusion time is an important parameter to consider when interpreting DWI data.
ABSTRACT
OBJECTIVE: This study investigated whether the metformin (Met)-induced enhanced intestinal uptake of 2-deoxy-2-[18F]fluoro-D-glucose (18F-FDG) is reduced by loperamide, a long-acting anti-diarrheal agent. METHODS: Mean 18F-FDG uptake in the mouse small intestine and colon with Met exposure was compared with that in control mice. In the Met group, high-dose (1.0 mg/kg body weight) and low-dose (0.1 mg/kg body weight) loperamide were introduced, and 18F-FDG uptake in the small intestine and colon was compared with that of control mice administered high-dose loperamide. The percent injected dose of 18F-FDG per gram of tissue (%ID/g) in the extracted tissues was then determined. RESULTS: 18F-FDG uptake increased significantly in the small intestine (0.64±0.06 vs. 1.01±0.15, p=0.040) and, especially, the colon (0.46±0.13 vs. 2.16±0.51, p<0.001) after Met exposure. Neither high-dose nor low-dose loperamide significantly reduced 18F-FDG uptake in the small intestine (0.82±0.31 vs. 0.84±0.22, p=0.93 and 0.78±0.25 vs. 0.70±0.15, p=0.13, respectively) or colon (2.13±0.41 vs. 1.67±0.55, p=0.063 and 1.77±0.39 vs. 1.80±0.25, p=0.56, respectively). The colonic %ID/g was significantly higher in Met groups irrespective of loperamide introduction than in control group, whereas the significant difference in the small intestine was observed only between Met and control groups. CONCLUSION: Metformin increased 18F-FDG uptake in intestines especially in colon. Loperamide administration partially, but not sufficiently, suppresses the Met-induced increased colonic uptake of 18F-FDG.
Subject(s)
Fluorodeoxyglucose F18/pharmacokinetics , Intestinal Absorption/drug effects , Intestinal Mucosa/metabolism , Intestines/drug effects , Loperamide/pharmacology , Metformin/pharmacology , Animals , Biological Transport/drug effects , Drug Interactions , Intestinal Mucosa/diagnostic imaging , Intestines/diagnostic imaging , Male , Mice , Mice, Inbred C57BL , Positron Emission Tomography Computed TomographyABSTRACT
This study evaluated the clinical significance of 18F-FDG PET/CT in patients with interstitial lung disease (ILD), by investigating the relationships between 18F-FDG PET/CT parameters and clinical indicators and by evaluating the prognostic implications of 18F-FDG PET/CT results. METHODS: Ninety patients (51 men, 39 women; mean age, 55.4 y; age range, 26-78 y) with ILD who underwent 18F-FDG PET/CT were retrospectively analyzed. SUVmean was defined as the mean SUV of the less-affected lung field, SUVTF as adjusted SUVmean using tissue fraction (TF), and CTmean as the mean attenuation of the corresponding region of interest on high-resolution CT. SUVmean, SUVTF, and CTmean were compared in the 90 ILD patients and in 15 age- and sex-matched controls. Correlations of SUVmax, SUVmean, SUVTF, and CTmean with clinical indicators, including estimated percentage of forced vital capacity (%FVC), estimated percentage of diffusion capacity of the lungs for carbon monoxide (%DLco), sialylated carbohydrate antigen Krebs von den Lungen-6 (KL-6), surfactant protein D (SP-D), C-reactive protein (CRP), lactate dehydrogenase (LDH), and ILD-sex-age-physiology (GAP) index, were evaluated using the Spearman rank correlation test and the Tukey-Kramer test. A Cox proportional hazards model was used for univariate and multivariate analyses of factors associated with lung transplantation-free survival. RESULTS: SUVmean, SUVTF, and CTmean were significantly higher in ILD patients than in healthy controls, except for CTmean in patients with a nonusual interstitial pneumonia pattern. SUVmean and CTmean were significantly correlated with %FVC, %DLco, KL-6, and SP-D; SUVTF was significantly correlated with %DLco, KL-6, SP-D, and LDH; and SUVmax was weakly correlated with KL-6 and CRP. Univariate analysis showed that SUVmean, SUVTF, sex, %FVC, %DLco, KL-6, and ILD-GAP index were significantly prognostic of lung transplantation-free survival; and multivariate analysis showed that SUVmean and ILD-GAP index were independently prognostic of lung transplantation-free survival. A higher SUVmean indicated a poorer prognosis, especially in patients with moderate risk based on ILD-GAP index. CONCLUSION: SUVmean was significantly but moderately correlated with clinical indicators, providing independent prognostic information in patients with ILD. 18F-FDG PET/CT may be helpful for monitoring and risk stratification of ILD patients.
Subject(s)
Fluorodeoxyglucose F18/metabolism , Lung Diseases, Interstitial/diagnosis , Lung Diseases, Interstitial/metabolism , Lung/metabolism , Adult , Aged , Biological Transport , Female , Humans , Lung/diagnostic imaging , Lung Diseases, Interstitial/diagnostic imaging , Male , Middle Aged , Observer Variation , Positron Emission Tomography Computed Tomography , Prognosis , Retrospective StudiesABSTRACT
OBJECTIVE: This study was designed to compare the clinical efficacy of (68)Ga-DOTA-Tyr-octreotide (DOTATOC)-positron emission tomography (PET)/computed tomography (CT) with that of conventional (67)Ga-scintigraphy (GS), and to correlate quantitative parameters on DOTATOC-PET/CT with clinical data, in patients with sarcoidosis. METHODS: Twenty patients who were histologically and/or clinically diagnosed with sarcoidosis and underwent both DOTATOC-PET/CT and GS were analyzed in this study. The numbers of patients with positive findings for each organ were determined. The total numbers of involved nodal areas in the chest, as determined by DOTATOC-PET and gallium single-photon emission tomography (Ga-SPECT), were compared. The correlations between quantitative parameters on PET and clinical laboratory data were evaluated. RESULTS: DOTATOC-PET/CT was positive in 19 patients, being negative in only one patient with chronic inactive sarcoidosis, whereas GS was positive in 17 patients. DOTATOC-PET/CT visualized more lesions in lymph nodes, uvea, and muscles than did Ga-scintigraphy and identified more involved areas than did GS-SPECT (p < 0.0001). Whole-body active lesion volume showed a significant, but moderate correlation with angiotensin-converting enzyme level (ρ = 0.64, p = 0.0044). CONCLUSIONS: PET/CT with DOTATOC may be superior to conventional GS in detecting sarcoidosis lesions, especially in lymph nodes, uvea, and muscles. Volumetric parameters in DOTATOC-PET/CT may be helpful in estimating the activity of sarcoidosis.