Functional imaging for assessment of therapy.

Functional imaging signals such as the regional uptake of the radiolabelled glucose analogue fluorodeoxyglucose (FDG), which can be noninvasively defined by positron emission tomography (PET), are suitable for the assessment of the response of tumour tissue to therapeutic interventions [1]. Therefore, in addition to its documented value in diagnosing tumour tissue, FDG-PET will have a major clinical impact through its role in therapy management. This prediction is supported by the fact that relatively little health care expenditure is used for the diagnosis of cancer compared with the large financial resources directed towards therapy. Imaging methods that will reduce the cost of therapy will help to manage oncological patients cost effectively. In addition to its promising clinical applications, PET also has an important role in clinical research. Based on the recommendations of the Director of the NCI for the fiscal budget of 2001, five particular opportunities for cancer research were identified. ‘‘Imaging of cancer’’ was chosen as the second most important. Closely related to this topic was ‘‘defining the signatures of cancer cells’’, which was also considered to be of future significance. The development of imaging signals to characterize tumour tissue and to define possible targets for therapy will emerge as an important academic challenge for the imaging community in the foreseeable future (see www. cancer.gov — budget section). However, PET is only one of many new imaging modalities being developed. Morphological imaging with CT and magnetic resonance tomography (MR) has advanced significantly over recent years, yielding excellent temporal and spatial resolution. At the same time, new imaging approaches have been introduced to provide a variety of functional signals, which can be used for non-invasive tissue characterization. Such signals include the qualitative and quantitative assessment of tissue perfusion, metabolism and signal transmission. New targets for imaging probes will emerge as our knowledge of biology increases. The identification of specific antigen and protein expression in tumour tissue will provide new stimuli for the visualization of tumour biology in vivo [2, 3]. Finally, as gene therapy becomes a clinical reality, there is a need for methods to monitor the efficacy of transfection as well as to assess protein expression, and the role of imaging is likely to expand [4]. As we progress from structural to biological imaging, several methods are in competition (Figure 1). The tracer approach using radioactive labelled compounds excels because of its high sensitivity. Picomolar concentrations of radiolabelled molecules can be detected in tissue, which compares favourably with MRI. However, the tracer approach is limited in specificity since radioisotopes can be separated from the labelled molecules by metabolic processes altering the regional distribution of the radioactivity. Optical imaging using fluorescence probes is most likely to compete in the future for the visualization of biological processes. However, the clinical application of this approach may be limited by the distance light can penetrate tissue [5]. The PET technology currently available produces tomographic images of the entire body, allowing visualization of regional metabolic processes with high spatial resolution (Figure 2). As a marker for glucose utilization, FDG provides high biological contrast between normal and malignant tissue. It has been known for many years that tumour tissue exhibits increased glucose uptake and glycolytic activity. This exciting new technology has gained wide clinical acceptance for diagnosing and localizing tumour tissue [6, 7]. However, its role in monitoring therapy is just now emerging. In this paper I will concentrate on the possible role of this modality to assist therapy in patients with cancer. What are the hypotheses that support the role of PET in therapy monitoring? Firstly, accurate staging of the tumour is necessary and will significantly influence the choice of therapy. Secondly, metabolic signals, such as FDG uptake, can be used to assess objectively the effect on therapy and tissue biochemistry. Several studies have shown that a decrease in metabolic activity precedes a change in tumour size [8]. Thirdly, it is necessary to identify residual tumour viability after therapy to define prognosis and to stratify the use of subsequent chemotherapy and radiotherapy. Finally, individual tissue characterization leading to the identification of therapy targets by The British Journal of Radiology, 75 (2002), S67–S73 E 2002 The British Institute of Radiology