86 research outputs found
Correlation of Dynamic PET and Gene Array Data in Patients with Gastrointestinal Stromal Tumors
Introduction. The results obtained with dynamic PET (dPET) were compared to gene expression data obtained in patients with gastrointestinal stromal tumors (GIST). The primary aim was to assess the association of the dPET results and gene expression data. Material and Methods. dPET was performed following the injection of F-18-fluorodeoxyglucose (FDG) in 22 patients with GIST. All patients were examined prior to surgery for staging purpose. Compartment and noncompartment models were used for the quantitative evaluation of the dPET examinations. Gene array data were based on tumor specimen obtained by surgery after the PET examinations. Results. The data analysis revealed significant correlations for the dPET parameters and the expression of zinc finger genes (znf43, znf85, znf91, znf189). Furthermore, the transport of FDG (k1) was associated with VEGF-A. The cell cycle gene cyclin-dependent kinase inhibitor 1C was correlated with the maximum tracer uptake (SUVmax) in the tumors. Conclusions. The data demonstrate a dependency of the tracer kinetics on genes associated with prognosis in GIST. Furthermore, angiogenesis and cell proliferation have an impact on the tracer uptake
Fractal and multifractal analysis of PET-CT images of metastatic melanoma before and after treatment with ipilimumab
PET/CT with F-18-Fluorodeoxyglucose (FDG) images of patients suffering from
metastatic melanoma have been analysed using fractal and multifractal analysis
to assess the impact of monoclonal antibody ipilimumab treatment with respect
to therapy outcome. Our analysis shows that the fractal dimensions which
describe the tracer dispersion in the body decrease consistently with the
deterioration of the patient therapeutic outcome condition. In 20 out-of 24
cases the fractal analysis results match those of the medical records, while 7
cases are considered as special cases because the patients have non-tumour
related medical conditions or side effects which affect the results. The
decrease in the fractal dimensions with the deterioration of the patient
conditions (in terms of disease progression) are attributed to the hierarchical
localisation of the tracer which accumulates in the affected lesions and does
not spread homogeneously throughout the body. Fractality emerges as a result of
the migration patterns which the malignant cells follow for propagating within
the body (circulatory system, lymphatic system). Analysis of the multifractal
spectrum complements and supports the results of the fractal analysis. In the
kinetic Monte Carlo modelling of the metastatic process a small number of
malignant cells diffuse throughout a fractal medium representing the blood
circulatory network. Along their way the malignant cells engender random
metastases (colonies) with a small probability and, as a result, fractal
spatial distributions of the metastases are formed similar to the ones observed
in the PET/CT images. In conclusion, we propose that fractal and multifractal
analysis has potential application in the quantification of the evaluation of
PET/CT images to monitor the disease evolution as well as the response to
different medical treatments.Comment: 38 pages, 9 figure
The cientificWorldJOURNAL Clinical Study Correlation of Dynamic PET and Gene Array Data in Patients with Gastrointestinal Stromal Tumors
Introduction. The results obtained with dynamic PET (dPET) were compared to gene expression data obtained in patients with gastrointestinal stromal tumors (GIST). The primary aim was to assess the association of the dPET results and gene expression data. Material and Methods. dPET was performed following the injection of F-18-fluorodeoxyglucose (FDG) in 22 patients with GIST. All patients were examined prior to surgery for staging purpose. Compartment and noncompartment models were used for the quantitative evaluation of the dPET examinations. Gene array data were based on tumor specimen obtained by surgery after the PET examinations. Results. The data analysis revealed significant correlations for the dPET parameters and the expression of zinc finger genes (znf43, znf85, znf91, znf189). Furthermore, the transport of FDG (k1) was associated with VEGF-A. The cell cycle gene cyclin-dependent kinase inhibitor 1C was correlated with the maximum tracer uptake (SUVmax) in the tumors. Conclusions. The data demonstrate a dependency of the tracer kinetics on genes associated with prognosis in GIST. Furthermore, angiogenesis and cell proliferation have an impact on the tracer uptake
Comparison between 68Ga-bombesin (68Ga-BZH3) and the cRGD tetramer 68Ga-RGD4 studies in an experimental nude rat model with a neuroendocrine pancreatic tumor cell line
BACKGROUND: Serotonergic neurons in the rodent hypothalamus are implicated in key neuroendocrine and metabolic functions, including circadian rhythmicity. However, the assessment of the serotonergic system in the human hypothalamus in vivo is difficult as delineation of the hypothalamus is cumbersome with conventional region-of-interest analysis. In the present study, we aimed to develop a method to visualize serotonin transporters (SERT) in the hypothalamus. Additionally, we tested the hypothesis that hypothalamic SERT binding ratios are different between patients with hypothalamic impairment (HI), pituitary insufficiency (PI), and control subjects (C). METHODS: SERT availability was determined in 17 subjects (6 HI, 5 PI, and 6 healthy controls), 2 h after injection of 123I-N-ω-fluoropropyl-2β-carboxymethoxy-3β-(4-iodophenyl) nortropane ([123I]FP-CIT), using single-photon emission computed tomography (performed on a brain-dedicated system) fused with individual magnetic resonance imaging (MRI) scans of the brain. The hypothalamus (representing specific SERT binding) and cerebellum (representing nonspecific binding) were manually delineated on each MRI to assess [123I]FP-CIT binding and specific-to-nonspecific binding ratios. RESULTS: In each healthy subject, [123I]FP-CIT binding was higher in the hypothalamus than in the cerebellum, and the mean hypothalamic binding ratio of SERT was 0.29 ± 0.23. We found no difference in hypothalamic binding ratios between HI, PI, and control subjects (HI 0.16 ± 0.24, PI 0.45 ± 0.39, C 0.29 ± 0.23, p value 0.281). CONCLUSIONS: We were able to demonstrate SERT binding in the human hypothalamus in vivo. However, we did not find altered hypothalamic SERT binding in patients with hypothalamic impairment. TRIAL REGISTRATION: Netherlands Trial Register: NTR2520
The Use of Positron Emission Tomography in Soft Tissue Sarcoma Patients under Therapy with Trabectedin
Background: We used 2-deoxy-2-[18F] fluoro-D-glucose (FDG) positron emission tomography (PET) to evaluate the FDG uptake in patients with advanced and/or metastatic soft tissue sarcoma (STS) undergoing therapy with Ecteinascidin-743 (ET-743, Trabectedin, YondelisTM). Patients and Methods: The pilot study included nine patients with metastatic STS receiving a minimum of one cycle of treatment with trabectedin. Patients were examined using PET prior to onset of therapy and after completion of one or three cycles of trabectedin. Restaging according to Response Evaluation Criteria in Solid Tumours (RECIST) was performed in parallel using computed tomography (CT) and/or magnetic resonance imaging (MRI) and served for reference. Results: Clinical outcome of nine evaluable patients was as follows: one patient with partial remission (PR), three patients with stable disease (SD), and five patients with progressive disease (PD). A more than 40% decrease of the standardized uptake value (SUV) of sequential PET examination could be demonstrated for the responding patient (PR), whereas patients with SD or PD showed a stable SUV, but no increase in SUV. Conclusion: To our knowledge, this is the first small series of patients being treated with trabectedin and monitored using sequential PET imaging demonstrating SUV stabilization in nearly all monitored patients
The Merendino procedure following preoperative imatinib mesylate for locally advanced gastrointestinal stromal tumor of the esophagogastric junction
68Ga-PSMA-11 Dynamic PET/CT Imaging in Primary Prostate Cancer.
PURPOSE
The aim of our study is to assess the pharmacokinetics and biodistribution of Ga-PSMA-11 in patients suffering from primary prostate cancer (PC) by means of dynamic and whole-body PET/CT.
MATERIALS AND METHODS
Twenty-four patients with primary, previously untreated PC were enrolled in the study. All patients underwent dynamic PET/CT (dPET/CT) scanning of the pelvis and whole-body PET/CT studies with Ga-PSMA-11. The evaluation of dPET/CT studies was based on qualitative evaluation, SUV calculation, and quantitative analysis based on two-tissue compartment modeling and a noncompartmental approach leading to the extraction of fractal dimension (FD).
RESULTS
A total of 23/24 patients (95.8%) were Ga-PSMA-11 positive. In 9/24 patients (37.5%), metastatic lesions were detected. PC-associated lesions demonstrated the following mean values: SUVaverage = 14.3, SUVmax = 23.4, K1 = 0.24 (1/min), k3 = 0.34 (1/min), influx = 0.15 (1/min), and FD = 1.27. The parameters SUVaverage, SUVmax, k3, influx, and FD derived from PC-associated lesions were significantly higher than respective values derived from reference prostate tissue. Time-activity curves derived from PC-associated lesions revealed an increasing Ga-PSMA-11 accumulation during dynamic PET acquisition. Correlation analysis revealed a moderate but significant correlation between PSA levels and SUVaverage (r = 0.60) and SUVmax (r = 0.57), and a weak but significant correlation between Gleason score and SUVaverage (r = 0.33) and SUVmax (r = 0.28).
CONCLUSION
Ga-PSMA-11 PET/CT confirmed its capacity in detecting primary PC with a detection rate of 95.8%. Dynamic PET/CT studies of the pelvis revealed an increase in tracer uptake in PC-associated lesions during the 60 minutes of dynamic PET acquisition, a finding with potential applications in anti-PSMA approaches
Application of an artificial intelligence-based tool in [18F]FDG PET/CT for the assessment of bone marrow involvement in multiple myeloma
Purpose: [18F]FDG PET/CT is an imaging modality of high performance in multiple myeloma (MM). Nevertheless, the inter-observer reproducibility in PET/CT scan interpretation may be hampered by the different patterns of bone marrow (BM) infiltration in the disease. Although many approaches have been recently developed to address the issue of standardization, none can yet be considered a standard method in the interpretation of PET/CT. We herein aim to validate a novel three-dimensional deep learning-based tool on PET/CT images for automated assessment of the intensity of BM metabolism in MM patients. Materials and methods: Whole-body [18F]FDG PET/CT scans of 35 consecutive, previously untreated MM patients were studied. All patients were investigated in the context of an open-label, multicenter, randomized, active-controlled, phase 3 trial (GMMG-HD7). Qualitative (visual) analysis classified the PET/CT scans into three groups based on the presence and number of focal [18F]FDG-avid lesions as well as the degree of diffuse [18F]FDG uptake in the BM. The proposed automated method for BM metabolism assessment is based on an initial CT-based segmentation of the skeleton, its transfer to the SUV PET images, the subsequent application of different SUV thresholds, and refinement of the resulting regions using postprocessing. In the present analysis, six different SUV thresholds (Approaches 1–6) were applied for the definition of pathological tracer uptake in the skeleton [Approach 1: liver SUVmedian
7 1.1 (axial skeleton), gluteal muscles SUVmedian
7 4 (extremities). Approach 2: liver SUVmedian
7 1.5 (axial skeleton), gluteal muscles SUVmedian
7 4 (extremities). Approach 3: liver SUVmedian
7 2 (axial skeleton), gluteal muscles SUVmedian
7 4 (extremities). Approach 4: ≥ 2.5. Approach 5: ≥ 2.5 (axial skeleton), ≥ 2.0 (extremities). Approach 6: SUVmax liver]. Using the resulting masks, subsequent calculations of the whole-body metabolic tumor volume (MTV) and total lesion glycolysis (TLG) in each patient were performed. A correlation analysis was performed between the automated PET values and the results of the visual PET/CT analysis as well as the histopathological, cytogenetical, and clinical data of the patients. Results: BM segmentation and calculation of MTV and TLG after the application of the deep learning tool were feasible in all patients. A significant positive correlation (p < 0.05) was observed between the results of the visual analysis of the PET/CT scans for the three patient groups and the MTV and TLG values after the employment of all six [18F]FDG uptake thresholds. In addition, there were significant differences between the three patient groups with regard to their MTV and TLG values for all applied thresholds of pathological tracer uptake. Furthermore, we could demonstrate a significant, moderate, positive correlation of BM plasma cell infiltration and plasma levels of β2-microglobulin with the automated quantitative PET/CT parameters MTV and TLG after utilization of Approaches 1, 2, 4, and 5. Conclusions: The automated, volumetric, whole-body PET/CT assessment of the BM metabolic activity in MM is feasible with the herein applied method and correlates with clinically relevant parameters in the disease. This methodology offers a potentially reliable tool in the direction of optimization and standardization of PET/CT interpretation in MM. Based on the present promising findings, the deep learning-based approach will be further evaluated in future prospective studies with larger patient cohorts
A phase II study evaluating neo-/adjuvant EIA chemotherapy, surgical resection and radiotherapy in high-risk soft tissue sarcoma
<p>Abstract</p> <p>Background</p> <p>The role of chemotherapy in high-risk soft tissue sarcoma is controversial. Though many patients undergo initial curative resection, distant metastasis is a frequent event, resulting in 5-year overall survival rates of only 50-60%. Neo-adjuvant and adjuvant chemotherapy (CTX) has been applied to achieve pre-operative cytoreduction, assess chemosensitivity, and to eliminate occult metastasis. Here we report on the results of our non-randomized phase II study on neo-adjuvant treatment for high-risk STS.</p> <p>Method</p> <p>Patients with potentially curative high-risk STS (size ≥ 5 cm, deep/extracompartimental localization, tumor grades II-III [FNCLCC]) were included. The protocol comprised 4 cycles of neo-adjuvant chemotherapy (EIA, etoposide 125 mg/m<sup>2 </sup>iv days 1 and 4, ifosfamide 1500 mg/m<sup>2 </sup>iv days 1 - 4, doxorubicin 50 mg/m<sup>2 </sup>day 1, pegfilgrastim 6 mg sc day 5), definitive surgery with intra-operative radiotherapy, adjuvant radiotherapy and 4 adjuvant cycles of EIA.</p> <p>Result</p> <p>Between 06/2005 and 03/2010 a total of 50 subjects (male = 33, female = 17, median age 50.1 years) were enrolled. Median follow-up was 30.5 months. The majority of primary tumors were located in the extremities or trunk (92%), 6% originated in the abdomen/retroperitoneum. Response by RECIST criteria to neo-adjuvant CTX was 6% CR (n = 3), 24% PR (n = 12), 62% SD (n = 31) and 8% PD (n = 4). Local recurrence occurred in 3 subjects (6%). Distant metastasis was observed in 12 patients (24%). Overall survival (OS) and disease-free survival (DFS) at 2 years was 83% and 68%, respectively. Multivariate analysis failed to prove influence of resection status or grade of histological necrosis on OS or DFS. Severe toxicities included neutropenic fever (4/50), cardiac toxicity (2/50), and CNS toxicity (4/50) leading to CTX dose reductions in 4 subjects. No cases of secondary leukemias were observed so far.</p> <p>Conclusion</p> <p>The current protocol is feasible for achieving local control rates, as well as OS and DFS comparable to previously published data on neo-/adjuvant chemotherapy in this setting. However, the definitive role of chemotherapy remains unclear in the absence of large, randomized trials. Therefore, the current regimen can only be recommended within a clinical study, and a possibly increased risk of secondary leukemias has to be taken into account.</p> <p>Trial registration</p> <p>ClinicalTrials.gov <a href="http://www.clinicaltrials.gov/ct2/show/NCT01382030">NCT01382030</a>, EudraCT 2004-002501-72</p
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