Elsevier

Molecular Imaging & Biology

Volume 5, Issue 4, July–August 2003, Pages 257-270
Molecular Imaging & Biology

Article
The value of positron emission tomography for monitoring response to radiotherapy in head and neck cancer

https://doi.org/10.1016/S1536-1632(03)00102-1Get rights and content

Abstract

Positron emission tomography (PET) is a molecular imaging technique that allows for accurate measurements of specific tissue functions. Staging of cancer using 2-deoxy-2-[18F]fluoro-D-glucose (FDG) is the most widely used diagnostic application. As PET is able to measure functional changes quantitatively, interest is growing in its use for monitoring response to therapy. This review describes both biologic characteristics of FDG and methodologic issues regarding its use in the head and neck region. In addition, the potential use of FDG for predicting and monitoring response to radiotherapy is discussed. Finally, the potential of some other tracers for monitoring response is reviewed.

Introduction

Radiotherapy is one of the cornerstones in the treatment of head and neck cancer. The goal of radiotherapy is to obtain tumor eradication while sparing normal tissue as much as possible. The probability to cure a patient by radiotherapy is determined by characteristics of the tumor (e.g., site, size, grade of differentiation, stage of disease, tumor oxygenation, and intrinsic radiosensitivity) and patient (e.g., weight loss, performance status, and comorbidity), but also by treatment-related factors, such as radiation dose and fractionation.

It would be of great value if the ultimate response to radiotherapy could be predicted, ideally prior to or early during treatment, to allow treatment modifications. Measurement of response in head and neck cancer has traditionally been performed using clinical, histologic and/or radiologic evaluation. Changes in tumor size and appearance, measurable with physical examination or anatomical imaging techniques (e.g., computed tomography [CT] and magnetic resonance imaging [MRI]), occur late during the course of radiotherapy, usually not before completion. In anatomical imaging, all voxels (volume elements) with a particular value represent a structural property of the tissue (e.g., attenuation characteristics, proton density), while with functional imaging the values represent a biochemical property. In contrast to changes in morphology, functional changes are anticipated earlier during treatment. Positron emission tomography (PET) is a quantitative functional imaging modality that provides the possibility to measure a wide range of tissue-specific parameters such as metabolism, receptor density, cell proliferation, and uptake of therapeutic agents with high sensitivity. Owing to its limited anatomical depiction, PET cannot replace other diagnostic procedures, but it does contribute valuable complementary diagnostic information.1 The advantage of PET compared with conventional techniques is the potential for early response monitoring, during and in the first weeks after completion of radiotherapy. In addition, it might be used for the prediction of response before the start of treatment.

Section snippets

FDG-PET

Central to PET is the use of tracers, which are labeled with positron-emitting isotopes. The most commonly used tracer in oncology is 2-deoxy-2-[18F]fluoro-D-glucose (FDG), an analog of glucose, which is transported into the cell and subsequently phosphorylated to FDG-6-PO4.

Before treatment

High intensity of FDG is strongly correlated with the proportion of cells in the S + G2/M-phase of the cell cycle (S = synthesis, G = gap, M = mitosis/proliferation),19 but a correlation between pretreatment accumulation and response to radiotherapy is far from clear. Small but statistically significant differences in proliferative fraction did not produce detectable differences in deoxyglucose incorporation, although a significant correlation was found between the S-phase fraction and deoxyglucose

Monitoring response using other PET tracers

Inflammation, which may be present in large amounts in the irradiated area, can also result in increased FDG uptake, thereby complicating interpretation of tumor response. Therefore, FDG might not be the ideal tracer to monitor response to radiotherapy. Beyond FDG, other specific characteristics can be imaged using PET, for instance, hypoxia. Hypoxia may be a cure-limiting factor in radiotherapy in HNSCC,78 because cells under anaerobic conditions are less sensitive to radiation. In 2000,

Discussion

High FDG uptake is strongly correlated with the proportion of cells in the proliferative phase of the cell cycle,19 but a correlation between accumulation and response to radiotherapy is far from clear. The fact that higher FDG uptake is associated with greater cell viability14., 15. and a higher propensity for cells to divide17., 20. may explain the poorer survival of patients with tumors with high FDG uptake.27., 67., 68., 69., 70., 71. Prospective studies are needed in large groups of

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