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Imaging of tumor hypoxia with [18F]HX4 PET

ABSTRACT: Primary objectives: Tumor to background ratio of [18F] HX4 PET images.

DISEASE(S): Eligible Patients With Histologically/cytologically Proven Primary Tumors Of The Prostate, Esophagus, Brain Or Rectum Or Metastatic Disease To The Brain (originating From Breast, Lung Or Colorectal).

PROVIDER: 2533706 | ecrin-mdr-crc |

REPOSITORIES: ECRIN MDR

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STING-driven interferon signaling triggers metabolic alterations in pancreas cancer cells visualized by [18F]FLT PET imaging

Project description:Type I interferons (IFNs) are critical effectors of emerging cancer immunotherapies designed to activate pattern recognition receptors (PRRs). A challenge in the clinical translation of these new immuno-modulatory agents is the lack of pharmacodynamic biomarkers indicative of increased intratumoral IFN signaling following PRR activation. Positron emission tomography (PET) imaging enables the visualization of tissue metabolic activity but whether IFN signaling-induced alterations in tumor cell metabolism can be detected using PET has not been investigated. We found that IFN signaling augments pancreatic ductal adenocarcinoma (PDAC) cell nucleotide metabolism via transcriptional induction of metabolism-associated genes including thymidine phosphorylase (TYMP). TYMP catalyzes the first step in the catabolism of thymidine which competitively inhibits intratumoral accumulation of the nucleoside analog PET probe [18F]-fluorothymidine ([18F]FLT). Accordingly, IFN treatment stimulates cancer cell [18F]FLT uptake in the presence of thymidine and this effect is dependent on TYMP expression. In vivo, genetic activation of stimulator of interferon genes (STING), a PRR widely expressed in PDAC, enhances the [18F]FLT avidity of xenograft tumors. Treatment with a small molecule STING agonist triggers IFN signaling-dependent TYMP expression in PDAC cells and enhances both subcutaneous and orthotopic tumor [18F]FLT uptake in vivo following systemic treatment. These findings indicate that [18F]FLT accumulation in tumors is sensitive to IFN signaling and that [18F]FLT PET may serve as a novel pharmacodynamic biomarker for PRR agonist-based immunotherapies in PDAC and possibly other malignancies characterized by elevated STING expression.

2021-08-30 | GSE178901 | GEO

68Ga-FAPI PET imaging assesses tumor immunity and guides TGF-β inhibition to sensitize metastatic colorectal cancer to immunotherapy

Project description:BACKGROUND. Improving and predicting tumor response to immunotherapy remains challenging. Combination therapy with a transforming growth factor β (TGF-β) inhibitor that targets cancer associated fibroblasts (CAFs) is promising to enhance efficacy of cancer immunotherapies. However, the effect of this approach in clinical trials is limited, requiring in vivo methods to better assess tumor responses to combination therapy. METHODS. We measure CAFs in vivo using gallium 68-labeled fibroblast activation protein inhibitor (68Ga-FAPI) for PET/CT imaging to guide TGF-β inhibition and sensitize metastatic colorectal cancer (CRC) to immunotherapy. A total of 131 patients with metastatic CRC underwent 68Ga-FAPI and 18F-fludeoxyglucose (18F-FDG) PET/CT imaging. Fourteen patients underwent surgery after the imaging. Relationship between uptake of 68Ga-FAPI and tumor immunity was analyzed. Mouse cohorts of metastatic CRC were treated with TGF-β receptor (TGF-βR) inhibitor combined with KN046 which blocks PD-L1 and CTLA4, followed with 68Ga-FAPI and 18F-FDG micro-PET/CT imaging to assess tumor responses. RESULTS. Patients with metastatic CRC demonstrated high uptakes of 68Ga-FAPI, along with suppressive tumor immunity and poor prognosis. TGF-βR inhibitor enhanced tumor infiltrating T cells and significantly sensitized metastatic CRC to KN046. 68Ga-FAPI PET/CT imaging accurately monitored the dynamical changes of CAFs and tumor response to combined TGF-βR inhibitor with immunotherapy. CONCLUSION. 68Ga-FAPI PET/CT imaging is powerful in assessing tumor immunity and response to immunotherapy in metastatic CRC. This study supports future clinical application of 68Ga-FAPI PET/CT to stratify and guide patients with CRC for precise TGF-β inhibition plus immunotherapy, recommending 68Ga-FAPI and 18F-FDG dual PET/CT for CRC management.

2023-12-19 | GSE247303 | GEO

Imaging tumor angiogenesis using 18F-Fluciclatide PET/CT in patients with colorectal and pancreatic cancer

Project description:Interventions: 18F-Fluciclatide PET scan Primary outcome(s): Assess feasibility and sensitivity of imaging tumor angiogenesis in PDAC and colorectal adenocarcinoma, using 18F-Fluciclatide. When successful, the data of this study will allow for a larger trial. Study Design: N/A: single arm study, Open (masking not used), N/A , unknown, Other

| 2442142 | ecrin-mdr-crc

Imaging tumor bloodvessels using 18F-Fluciclatide PET scan.

Project description:Primary objectives: Assess feasibility and sensitivity of imaging tumor angiogenesis in PDAC and colorectal adenocarcinoma, using 18F-Fluciclatide. When successful, the data of this study will allow for a larger trial. Primary endpoints: Sensitivity of 18F-Fluciclatide.

| 2538508 | ecrin-mdr-crc

STING-driven interferon signaling triggers metabolic alterations in pancreas cancer cells visualized by [18F]FLT PET imaging

Project description:STING-driven interferon signaling triggers metabolic alterations in pancreas cancer cells visualized by [18F]FLT PET imaging

| PRJNA741475 | ENA

Genomic signature of the standardized uptake value in 18F-fluorodeoxyglucose positron emission tomography in breast cancer

Project description:The standardized uptake value (SUV), an indicator of the glucose uptake degree in 18F-fluorodeoxyglucose positron emission tomography (FDG-PET), has been used as a prognostic factor in malignant tumors. We aimed to identify a signature reflecting prognostic SUV characteristics in breast cancer (BRC). Transcriptome profiling was performed to identify a signature associated with the SUV in BRC patients who underwent preoperative FDG-PET. We defined a signature consisting of 723 genes significantly correlated with the SUV (|r| > .35; P < .001). The patient subgroups classified by the signature were significantly similar to those classified by the SUV (odds ratio, 8.02; 95% CI, 2.45 to 29.3; P < 0.001). The SUV signature showed independent clinical utility for predicting BRC prognosis (hazard ratio, 1.25; 95% CI, 1.11 to 1.42; P < 0.001). Integrative analysis demonstrated a significance of the signature in predicting the response to immunotherapy and revealed that a signaling axis defined by TP53-FOXM1 and its downstream effectors in glycolysis-gluconeogenesis, including LDHA, might be important mediators in the FDG-PET process. Our results reveal characteristics of glucose uptake captured by FDG-PET, supporting an understanding of glucose metabolism as well as poor prognosis in BRC patients with a high SUV.

2020-03-18 | GSE131769 | GEO

18F-Fluoroazomycin Arabinoside PET-CT in Diagnosing Solid Tumors in Patients

Project description:This early phase I trial studies how well 18F-fluoroazomycin arabinoside positron emission tomography (PET)-computed tomography (CT) works in diagnosing solid tumors. Using 18F-fluoroazomycin arabinoside with PET-CT may help doctors plan better treatment for patients with solid tumors. 18F-fluoroazomycin arabinoside may help to show how much oxygen is present in a tumor during a PET-CT scan.

| 2245574 | ecrin-mdr-crc

Molecular imaging of lymphoid organs and immune activation using PET with a new 18F-labeled 2’-deoxycytidine analog

Project description:Differential gene expression between naive and activated CD8+ T cells was assessed using microarray analysis to determine target genes for new positron emission tomography (PET) probe screening, in particular for molecular imaging of lymphoid organs and immune activation. Keywords: cell activation comparison

2008-01-15 | GSE9997 | GEO

imaging characteristics and prognostic value of isolated pulmonary metastasis from colorectal cancer demonstrated with 18F-FDG PET/CT

Project description:Interventions: Gold Standard:Pathological diagnosis;Index test:18F-FDG PET-CT Primary outcome(s): Overall survival rate Study Design: Sequential

| 2705260 | ecrin-mdr-crc

18F-Fluoromisonidazole in tumor hypoxia imaging.

Project description:Hypoxia is a common feature of solid tumors that is closely associated with radiotherapy and chemotherapy resistance, metastasis and tumors prognosis. Thus, it is important to assess hypoxia in tumors for estimating prognosis and selecting appropriate treatment procedures. 18F-Fluoromisonidazole positron emission tomography (18F-FMISO PET) has been widely used to visualize tumor hypoxia in a comprehensive and noninvasive way, both in the clinical and preclinical settings. Here we review the concept, mechanisms and detection methods of tumor hypoxia. Furthermore, we discuss the correlation between 18F-FMISO PET and other detection methods, current applications of 18F-FMISO PET and the development prospects of this imaging technology.

| S-EPMC5706929 | biostudies-other

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