Imaging tumor angiogenesis using 18F-Fluciclatide PET/CT in patients with colorectal and pancreatic cancer
Ontology highlight
ABSTRACT:
DISEASE(S): Colorectal Cancer,Pancreatic Cancer
PROVIDER: 2442142 | ecrin-mdr-crc |
REPOSITORIES: ECRIN MDR
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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.
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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
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
Project description:Measuring tumor response to treatment based on computed tomography (CT) and/or magnetic resonance imaging (MRI) has been a widely debated issue (response criteria in solid tumors [RECIST] and World Health Organization criteria). Furthermore, early identification of nonresponding patients is of great importance because the rates of response of common malignant solid tumors to chemotherapy are in the range of only 20-30%. Therefore, quantitative imaging of tumor metabolism with 18F-FDG PET/CT may provide important advantages and thus reduce side effects and costs of ineffective therapy. However, the evidence to date for the use of 18F-FDG-PET/CT with this indication is limited.
The purpose of the present trial is to determine the impact of 18F-FDG PET/CT in the management of advanced colorectal cancer. The aim is also to confirm whether a metabolic response can be used as a surrogate end point in monitoring treatment response in this cancer type.
The study consists of 40 patients with advanced colorectal cancer patients. All patients will be studied with 18F-FDG PET/CT combined with diagnostic contrast enhanced abdominal CT before the start of chemotherapy and re-evaluated 4-5 weeks after the initiation of therapy. Effect of this metabolic and anatomic change in therapy are evaluated and correlated to survival, morbidity, and treatment -related costs. Histopathologic confirmation of response is evaluated whenever possible. The data will be collected between 2008 and 2012.
| 2066434 | ecrin-mdr-crc
Project description:The purpose of this study was to compare the diagnostic performance of 18F-DCFBC PET/CT, a first-generation 18F-labeled prostate-specific membrane antigen (PSMA)-targeted agent, and 18F-NaF PET/CT, a sensitive marker of osteoblastic activity, in a prospective cohort of patients with metastatic prostate cancer. Methods: Twenty-eight prostate cancer patients with metastatic disease on conventional imaging prospectively received up to 4 PET/CT scans. All patients completed baseline 18F-DCFBC PET/CT and 18F-NaF PET/CT scans, and 23 patients completed follow-up imaging, with a median follow-up interval of 5.7 mo (range, 4.2-12.6 mo). Lesion detection was compared across the 2 PET/CT agents at each time point. Detection and SUV characteristics of each PET/CT agent were compared with serum prostate-specific antigen (PSA) levels and treatment status at the time of baseline imaging using nonparametric statistical testing (Spearman correlation, Wilcoxon rank). Results: Twenty-six patients had metastatic disease detected on 18F-NaF or 18F-DCFBC at baseline, and 2 patients were negative on both scans. Three patients demonstrated soft tissue-only disease. Of 241 lesions detected at baseline, 56 were soft-tissue lesions identified by 18F-DCFBC only and 185 bone lesions detected on 18F-NaF or 18F-DCFBC. 18F-NaF detected significantly more bone lesions than 18F-DCFBC (P < 0.001). Correlation of PSA with patient-level SUV metrics was strong in 18F-DCFBC (? > 0.5, P < 0.01) and poor in 18F-NaF (? < 0.3, P > 0.1). When PSA levels were combined with treatment status, patients with below-median levels of PSA (<2 ng/mL) on androgen deprivation therapy (n = 11) demonstrated more lesions on 18F-NaF than 18F-DCFBC (P = 0.02). In PSA greater than 2 ng/mL, patients on androgen deprivation therapy (n = 8) showed equal to or more lesions on 18F-DCFBC than on 18F-NaF. Conclusion: The utility of PSMA-targeting imaging in metastatic prostate cancer appears to depend on patient disease course and treatment status. Compared with 18F-NaF PET/CT, 18F-DCFBC PET/CT detected significantly fewer bone lesions in the setting of early or metastatic castrate-sensitive disease on treatment. However, in advanced metastatic castrate-resistant prostate cancer, 18F-DCFBC PET/CT shows good concordance with NaF PET/CT.
| S-EPMC6225539 | biostudies-literature
Project description:PET/CT imaging is frequently used for cancer diagnosis and restaging as metabolically active cells, including cancer, utilize glucose for proliferation. F-FDG is the most commonly utilized radiopharmaceutical in PET/CT imaging. Limitations of F-FDG imaging include intense physiologic uptake in benign tissues such as the brain and myocardium. We present a case of non-small cell lung cancer with myocardial and pericardial metastases obscured by physiologic F-FDG cardiac uptake but detected with the investigational PET radiotracer (4S)-4-(3-F-fluoropropyl)-L-glutamate (F-FSPG), which targets a pathway associated with glutathione biosynthesis. This case demonstrates the added value of F-FSPG PET/CT imaging.
| S-EPMC5716866 | biostudies-literature
Project description:Summary:Pheochromocytoma (PHEO) in multiple endocrine neoplasia type 1 (MEN1) is extremely rare. The incidence is reported as less than 2%. We report a case of a 76-year-old male with familial MEN1 who was found to have unilateral PHEO. Although the patient was normotensive and asymptomatic, routine screening imaging with CT demonstrated bilateral adrenal masses. The left adrenal mass grew from 2.5 to 3.9 cm over 4 years with attenuation values of 9 Hounsfield units (HU) pre-contrast and 15 HU post-contrast washout. Laboratory evaluation demonstrated an adrenergic biochemical phenotype. Both 18F-fluorodeoxyglucose (18F-FDG) PET/CT and 123I-metaiodobenzylguanidine (123I-mIBG) scintigraphy demonstrated bilateral adrenal uptake. In contrast, 18F-fluorodihydroxyphenylalanine (18F-FDOPA) PET/CT demonstrated unilateral left adrenal uptake (28.7 standardized uptake value (SUV)) and physiologic right adrenal uptake. The patient underwent an uneventful left adrenalectomy with pathology consistent for PHEO. Post-operatively, he had biochemical normalization. A review of the literature suggests that adrenal tumors >2 cm may be at higher risk for pheochromocytoma in patients with MEN1. Despite a lack of symptoms related to catecholamine excess, enlarging adrenal nodules should be biochemically screened for PHEO. 18F-FDOPA PET/CT may be beneficial for localization in these patients. Learning points:18F-FDOPA PET/CT is a beneficial imaging modality for identifying pheochromocytoma in MEN1 patients. Adrenal adenomas should undergo routine biochemical workup for PHEO in MEN1 and can have serious peri-operative complications if not recognized, given that MEN1 patients undergo frequent surgical interventions. MEN1 is implicated in the tumorigenesis of PHEO in this patient.
| S-EPMC7077596 | biostudies-literature
Project description:Context:MYC-associated factor X (MAX) has been recently described as a new susceptibility pheochromocytoma (PHEO) gene with a total of ~40 reported cases. At present, no study has specifically described the functional imaging phenotype of MAX-related PHEO. Objective, Patients, and Design:The objective of the present study was to present our experience with contrast-enhanced computed tomography (CT) and 18F-fluorodihydroxyphenylalanine (18F-FDOPA) positron emission tomography (PET)/CT in six consecutive patients (four at the initial diagnosis and two at the follow-up evaluation) with rare, but clinically important, MAX-related PHEOs. In five patients, 18F-FDOPA was also compared with other radiopharmaceutical agents. Results:The patients had five different mutations in the MAX gene that caused disruption of Max/Myc interaction and/or abolished interaction with DNA based on in silico analyses. All but one patient developed bilateral PHEOs during their lifetime. In all cases, 18F-FDOPA PET/CT accurately visualized PHEOs that were often multiple within the same gland or bilaterally and detected more adrenal and extra-adrenal lesions than did CT (per-lesion sensitivity, 90.9% vs 52.4% for CT/magnetic resonance imaging). The two PHEOs missed on 18F-FDOPA PET/CT were <1 cm, corresponding to nodular adrenomedullary hyperplasia. 68Ga-DOTA,Tyr3-octreotate PET/CT detected fewer lesions than did 18F-FDOPA PET/CT in one of three patients, and 18F-fluorodeoxyglucose PET/CT was only faintly positive in two of four patients with underestimation of extra-adrenal lesions in one patient. Conclusions:MAX-related PHEOs exhibit a marked 18F-FDOPA uptake, a finding that illustrates the common well-differentiated chromaffin pattern of PHEOs associated with activation of kinase signaling pathways. 18F-FDOPA PET/CT should be considered as the first-line functional imaging modality for diagnostic or follow-up evaluations for these patients.
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Project description:Pleural epithelioid hemangioendothelioma (EHE) is a rare malignancy of vascular-endothelial origin with non-specific symptoms and an unpredictable outcome. Diagnosis of this condition by imaging modalities is challenging, and no standard therapeutic approaches have been established in this regard. In this paper, we described the case of a patient with a low-grade fever, coughing and chest pain who underwent 18F-FDG PET/CT after a positive thorax CT showing multiple bilateral calcified pulmonary nodules and extensive right-sided pleural effusion. Moreover, PET/CT revealed increased tracer uptake on the nodular pleural thickening and one nodule in the upper lobe of the right lung. A diagnostic thoracentesis was performed to obtain the pleural fluid. However, cytology was not diagnostic, and the subsequent thoracotomy with pleural fluid drainage and pleural biopsy was positive for pleural EHE. The study showed also an abundant non-FDG-avid pleural effusion in the collapsed right lung. Despite chest tube insertion and partial drainage of the volume, patient's condition deteriorated, and patient passed away six months after the PET scan.
| S-EPMC5221689 | biostudies-other
Project description:PurposeTo evaluate if the new Discovery Molecular Insights (DMI) PET/CT scanner provides equivalent results compared to the standard of care PET/CT scanners (GE Discovery 600 or GE Discovery 690) used in our clinic and to explore any possible differences in semi-quantitative measurements.MethodsThe local Institutional Review Board approved the protocol and written informed consent was obtained from each patient. Between September and November 2016, 50 patients underwent a single 18F-FDG injection and two scans: the clinical standard PET/CT followed immediately by the DMI PET/CT scan. We measured SUVmax and SUVmean of different background organs and up to four lesions per patient from data acquired using both scanners.ResultsDMI PET/CT identified all the 107 lesions detected by standard PET/CT scanners, as well as additional 37 areas of focal increased 18F-FDG uptake. The SUVmax values for all 107 lesions ranged 1.2 to 14.6 (mean ± SD: 2.8 ± 2.8), higher on DMI PET/CT compared with standard of care PET/CT. The mean lesion:aortic arch SUVmax ratio and mean lesion:liver SUVmax ratio were 0.2-15.2 (mean ± SD: 3.2 ± 2.6) and 0.2-8.5 (mean ± SD: 1.9 ± 1.4) respectively, higher on DMI PET/CT than standard PET/CT. These differences were statistically significant (P value < 0.0001) and not correlated to the delay in acquisition of DMI PET data (P < 0.0001).ConclusionsOur study shows high performance of the new DMI PET/CT scanner. This may have a significant role in diagnosing and staging disease, as well as for assessing and monitoring responses to therapies.
| S-EPMC5459477 | biostudies-literature