Abstract

ObjectivesHypoxia in solid tumors occurs when metabolic demands in tumor cells surpass the delivery of oxygenated blood. We hypothesize that the 18F-fluorodeoxyglucose (18F-FDG) metabolism and tumor blood flow mismatch would correlate with tumor hypoxia.MethodsLiver perfusion computed tomography (CT) and 18F-FDG positron emission tomography (PET) imaging were performed in twelve rabbit livers implanted with VX2 carcinoma. Under CT guidance, a fiber optic probe was inserted into the tumor to measure the partial pressure of oxygen (pO2). Tumor blood flow (BF) and standardized uptake value (SUV) were measured to calculate flow-metabolism ratio (FMR). Tumor hypoxia was further identified using pimonidazole immunohistochemical staining. Pearson correlation analysis was performed to determine the correlation between the imaging parameters and pO2 and pimonidazole staining.ResultsWeak correlations were found between blood volume (BV) and pO2 level (r = 0.425, P = 0.004), SUV and pO2 (r = -0.394, P = 0.007), FMR and pimonidazole staining score (r = -0.388, P = 0.031). However, there was stronger correlation between tumor FMR and pO2 level (r = 0.557, P < 0.001).ConclusionsFMR correlated with tumor oxygenation and pimonidazole staining suggesting it may be a potential hypoxic imaging marker in liver tumor.

Highlights

  • Hypoxia, a hallmark of malignant diseases, is highly associated with an aggressive tumor phenotype and therapeutic resistance [1]

  • Weak correlations were found between blood volume (BV) and pO2 level (r = 0.425, P = 0.004), standardized uptake value (SUV) and pO2 (r = -0.394, P = 0.007), flow-metabolism ratio (FMR) and pimonidazole staining score (r = -0.388, P = 0.031)

  • FMR correlated with tumor oxygenation and pimonidazole staining suggesting it may be a potential hypoxic imaging marker in liver tumor

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Summary

Introduction

A hallmark of malignant diseases, is highly associated with an aggressive tumor phenotype and therapeutic resistance [1]. A variety of invasive and non-invasive methods have been developed to detect and monitor spatial and temporal hypoxia in tumors, including biological markers and non-invasive imaging techniques [2]. Positron emission tomography (PET) imaging has been investigated for imaging tumor hypoxia using a variety of tracers, including 18F-fluoroazomycinarabino-furanoside (18F-FMISO), 18F-fluoroazomycinarabinofuranoside (18F-FAZA) and Cu (II)-diacetyl-(N4-methylthiosemicarbazone (Cu-ATSM). Most PET hypoxia tracers show unfavourable results in liver hypoxia imaging. No imaging modalities have been recommended for imaging liver tumor hypoxia in clinical practice

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