Dataset Information

Prognostic PET [¹¹C]-acetate uptake is associated with hypoxia gene expression in patients with late-stage hepatocellular carcinoma - a bench to bed study.

ABSTRACT:

Background

Positron Emission Tomography (PET) with combined [¹⁸F]-FDG and [¹¹C]-acetate (dual-tracer) is used for the management of hepatocellular carcinoma (HCC) patients, although its prognostic value and underlying molecular mechanism remain poorly understood. We hypothesized that radiotracer uptake might be associated with tumor hypoxia and validated our findings in public and local human HCC cohorts.

Methods

Twelve orthotopic HCC xenografts were established using MHCC97L cells in female nude mice, with 5 having undergone hepatic artery ligation (HAL) to create tumor hypoxia in vivo. Tumors in both Control and HAL-treated xenografts were imaged with [¹¹C]-acetate and [¹⁸F]-FDG PET-MR and RNA sequencing was performed on the resected tumors. Semiquantitative analysis of PET findings was then performed, and the findings were then validated on the Cancer Genome Atlas Liver Hepatocellular Carcinoma (TCGA-LIHC) cohort and patients from our institution.

Results

HAL-treated mice showed lower [¹¹C]-acetate (HAL-treated vs. Control, tumor-to-liver SUV ratio (SUV_TLR): 2.14[2.05-2.21] vs 3.11[2.75-5.43], p = 0.02) but not [¹⁸F]-FDG (HAL-treated vs. Control, SUV_TLR: 3.73[3.12-4.35] vs 3.86[3.7-5.29], p = 0.83) tumor uptakes. Gene expression analysis showed the PET phenotype is associated with upregulation of hallmark hypoxia signature. The prognostic value of the hypoxia gene signature was tested on the TCGA-LIHC cohort with upregulation of hypoxia gene signature associated with poorer overall survival (OS) in late-stage (stage III and IV) HCC patients (n = 66, OS 2.05 vs 1.67 years, p = 0.046). Using a local cohort of late-stage HCC patients who underwent dual-tracer PET-CT, tumors without [¹¹C]-acetate uptake are associated with poorer prognosis (n = 51, OS 0.25 versus 1.21 years, p < 0.0001) and multivariable analyses showed [¹¹C]-acetate tumor uptake as an independent predictor of OS (HR 0.17 95%C 0.06-0.42, p < 0.0001).

Conclusions

[¹¹C]-acetate uptake is associated with alteration of tumor hypoxia gene expression and poorer prognosis in patients with advanced HCC.

SUBMITTER: Chiu KWH

PROVIDER: S-EPMC10958914 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature

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Publications

Prognostic PET [<sup>11</sup>C]-acetate uptake is associated with hypoxia gene expression in patients with late-stage hepatocellular carcinoma - a bench to bed study.

Chiu Keith Wan Hang KWH Tan Kel Vin KV Yang Xinxiang X Zhu Xiaoqiang X Shi Jingjing J Chiang Chi-Leung CL Chan Lawrence L Hui Yuan Y Khong Pek-Lan PL Man Kwan K Wong Jason Wing Hon JWH

Cancer imaging : the official publication of the International Cancer Imaging Society 20240322 1

<h4>Background</h4>Positron Emission Tomography (PET) with combined [<sup>18</sup>F]-FDG and [<sup>11</sup>C]-acetate (dual-tracer) is used for the management of hepatocellular carcinoma (HCC) patients, although its prognostic value and underlying molecular mechanism remain poorly understood. We hypothesized that radiotracer uptake might be associated with tumor hypoxia and validated our findings in public and local human HCC cohorts.<h4>Methods</h4>Twelve orthotopic HCC xenografts were establis ...[more]

PMID: 38520026

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Project description:ObjectiveThis study aims to explore the difference between 11C-methyl-N-2β-carbomethoxy-3β-(4-fluorophenyl)-tropanel (11C-CFT) positron emission tomography (PET) imaging in the early-onset Parkinson's disease (EOPD) and late-onset Parkinson's disease (LOPD), and to analyze the correlation between 11C-CFT PET imaging and disease duration, Hoehn & Yahr (H&Y) stage, motor symptoms, and non-motor symptoms in patients with idiopathic Parkinson's disease (PD), so as to explore its application value in assessing the severity of Parkinson's disease.Materials and methodsA total of 113 patients with idiopathic PD were included in this study. The patients were divided into EOPD and LOPD groups according to the age of 60 years, of which 58 were early-onset and 55 were late-onset. All patients underwent 11C-CFT PET imaging and manually sketched regions of interest (ROI) to delineate the caudate nucleus, anterior putamen, and posterior putamen ROI layer-by-layer, and the corresponding values were recorded. Clinical data [age of onset, disease duration, H&Y stage, total Unified Parkinson's Disease Rating Scale (UPDRS) score, UPDRS III score, tremor score, postural instability/gait difficulty (PIGD) score, rigidity score, bradykinesia score, and Montreal Cognitive Assessment (MoCA) score] were collected from all patients. The differences in striatal 11C-CFT uptake between patients with EOPD and LOPD were compared, and the correlation between striatal 11C-CFT uptake and the clinical data of patients with idiopathic PD was evaluated.ResultsThe caudate nucleus 11C-CFT uptake was higher in EOPD than in the LOPD group (t = 3.002, p = 0.003). 11C-CFT uptake in the caudate nucleus in patients with PD was negatively correlated with the age of onset, H&Y stage, disease duration, total UPDRS score, UPDRS III score, rigidity score, and bradykinesia score (p < 0.05). The anterior and posterior putamen 11C-CFT uptake was negatively correlated with H&Y stage, disease duration, total UPDRS score, UPDRS III score, PIGD score, rigidity score, and bradykinesia score (p < 0.05).Conclusion11C-CFT PET provides an objective molecular imaging basis for the difference in disease progression rates between patients with EOPD and LOPD. Secondly, 11C-CFT PET can be used as an important objective indicator to assess disease severity and monitor disease progression.

Dataset Information

Prognostic PET [¹¹C]-acetate uptake is associated with hypoxia gene expression in patients with late-stage hepatocellular carcinoma - a bench to bed study.

Background

Methods

Results

Conclusions

Publications

Prognostic PET [<sup>11</sup>C]-acetate uptake is associated with hypoxia gene expression in patients with late-stage hepatocellular carcinoma - a bench to bed study.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

Prognostic PET [11C]-acetate uptake is associated with hypoxia gene expression in patients with late-stage hepatocellular carcinoma - a bench to bed study.

Background

Methods

Results

Conclusions

Publications

Prognostic PET [<sup>11</sup>C]-acetate uptake is associated with hypoxia gene expression in patients with late-stage hepatocellular carcinoma - a bench to bed study.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Prognostic PET [¹¹C]-acetate uptake is associated with hypoxia gene expression in patients with late-stage hepatocellular carcinoma - a bench to bed study.