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Commentary |
Department of Nuclear Medicine, Royal Marsden Hospital, Downs Road, Sutton, Surrey SM2 5PT, UK
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Introduction |
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 Top Introduction References |
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The glucose analogue 18F-fluorodeoxyglucose (18FDG) is currently used for the vast majority of clinical PET studies, particularly in oncology. Malignant cells have a higher glycolytic rate [1], and overexpression of membrane glucose transporters such as GLUT 1 has been described in a number of cancers, leading to high uptake of this tracer compared with normal tissues [2]. As a functional technique, 18FDG PET relies primarily on metabolic activity rather than size for detection of malignancy and, as a result, is inherently more sensitive than anatomical modalities such as CT. For example, it is possible to detect malignant involvement in lymph nodes that are not enlarged by CT criteria and, conversely, only low grade or absent uptake is shown in enlarged, reactive nodes. Of course, increased glycolysis is not specific to malignant tissue and some benign conditions may mimic malignancy, but this is not a common problem in practice.
One clinical application in which 18FDG PET was first shown to be cost effective was the evaluation of indeterminate pulmonary nodules where, in spite of the additional cost of the PET scan, it was estimated that a saving of up to $2200 per patient could be made [3]. 18FDG PET is also of potential benefit as a "metabolic biopsy" tool in regions of the body that are either inaccessible or where biopsy is contraindicated, or when diagnostic tissue is not obtained.
It is the sensitivity of 18FDG PET that enables it to be cost effective and to change patient management in the pre-operative staging of a number of cancers [4]. This is particularly true in cancers with a high relapse rate after "curative" surgery, i.e. in those in which small volumes of metastatic disease were not identified by conventional means. There are now enough data to suggest that some groups of patients, for example those with non-small cell lung cancer and recurrent colorectal cancer [5], should not undergo an attempted curative operation without an 18FDG PET scan. The pre-operative detection of non-resectable tumour may avoid unnecessary surgery, allowing the patient to be directed towards a more appropriate treatment regimen at an earlier stage. There is, of course, a limit to the sensitivity of PET, and it is not possible to identify microscopic disease. For example, sentinel node scintigraphy is superior in staging regional lymph nodes in melanoma [6].
18FDG PET does not show a higher sensitivity in all cancers when compared with conventional imaging techniques. Some tumours, such as neuroendocrine tumours and skeletal metastases from prostate cancer, have limited avidity for 18FDG, and other methods may be more appropriate for optimal staging. As positron emitters include organic elements such as nitrogen, oxygen and carbon, PET radiochemisty is very versatile and it is possible that alternative tracers will be developed for specific tumours in the future.
In view of the limited availability of PET at the present time, many referrals are for problem-solving rather than for routine applications, particularly from those centres without a PET facility on site. Indications where the sensitivity and specificity of 18FDG PET have the potential to make a significant contribution to patient management include the detection of otherwise occult recurrent cancer in those patients with rising tumour markers or for the characterization of residual masses following chemotherapy. 18FDG PET may also be useful in patients in whom there is a strong suspicion of malignancy that is not detectable by other means, for example paraneoplastic syndromes, or in those in whom a metastasis has been identified but the site of the primary tumour is unclear. Although the differentiation of post-treatment gliosis from recurrent tumour is a valid indication for evaluating primary brain tumours, optimally with a combination of 18FDG and 11C-methionine, the detection of metastatic disease in the brain is still the province of MRI and CT. The high uptake of 18FDG into normal cortex renders PET relatively insensitive for detecting cerebral metastases.
The role of PET in evaluating the effects of cancer treatment is still an underinvestigated area. As a functional technique, PET has the potential to accurately evaluate disease response at an early stage, perhaps after one or two cycles of chemotherapy. This would allow a change to more effective treatment in those who are not responding, thereby avoiding morbidity from inappropriately prolonged treatment from which there will be no benefit. Although there may be a role for 18FDG in this regard, there is great interest in the development of novel tracers for evaluating tumour proliferation, angiogenesis and apoptosis that may be more sensitive markers of tumour response to specific drugs.
Outside oncology, 18FDG PET remains the gold standard non-invasive method for differentiating myocardium that is viable but hibernating from that which is non-viable in patients with coronary artery disease and a history of infarction. It has the potential to accurately categorize those with viable, hibernating myocardium who may benefit symptomatically, functionally and prognostically from revascularisation procedures from those in whom the only alternative is cardiac transplantation.
The clinical potential for PET is less certain in neurology (excluding neuro-oncology) and psychiatry. PET techniques may be valuable in individual cases of dementia and in the planning of surgery for resistant epilepsy, but the role is less clear cut than in oncology.
In spite of the undoubted benefit of PET to medicine, access is currently limited to only a few centres in the UK. The half-life of 18FDG is 110 min, which means that it is possible to transport this tracer a reasonable distance by road to departments without a cyclotron. However, the supply of 18FDG is limited at present and depends on those centres that have their own cyclotron and have 18FDG surplus to their own needs. The relatively limited supply may be one of the reasons why the number of clinical PET facilities has not grown at a faster rate in this country, as not all interested groups have the means to purchase and run their own cyclotron. It can only be a matter of time before 18FDG becomes available from a commercial network, as in the USA, but presumably the radiophamaceutical companies are awaiting a critical mass of potential customers and scanners, a "chicken and egg" situation.
PET is perceived as an expensive clinical investigation. Currently in the UK the cost per 18FDG PET scan is of the order of £800–1000. Despite this, a number of studies have reported the cost effectiveness of 18FDG PET in oncology in the USA where the reimbursement fee is $2000 (
£1300). These cost savings are largely due to the high sensitivity of 18FDG PET for detecting hitherto unknown sites of disease prior to surgical or medical treatment, and have lead to a number of oncological applications being reimbursable in the USA. As a way of reducing the capital costs compared with a dedicated PET system, much effort has been put into the development of hybrid gamma cameras that allow imaging of both conventional single photon nuclear medicine tracers as well as PET tracers. The latter are detected by using coincidence electronics in opposing heads of dual headed cameras. There is no doubt that the performance of these sodium iodide hybrid cameras is inferior to dedicated bismuth germanate PET systems, with most clinical comparisons showing a drop in sensitivity of tumours below approximately 2 cm. A role for hybrid gamma cameras may exist for differentiating benign from malignant masses that are larger than this, or for assessing the effects of treatment in large masses. However, the role in staging cancers will be limited compared with dedicated PET, which has unequivocal advantages over current anatomical staging methods [4]. In spite of initial enthusiasm in the USA for the lower cost option of hybrid gamma cameras, mobile dedicated PET scanners are now gaining popularity, particularly in centres where the workload does not justify the cost of a permanent installation. Although this might be a short-term remedy to increase the availability of PET in the UK, one of a number of possible longer term alternatives would be to have dedicated PET facilities installed at major cancer centres. However, there are large capital, training and staffing resource implications for such a plan, even if studies that are now underway show that 18FDG PET is as cost effective in the National Health Service of the UK as it is in the USA.
An impressive body of information now shows that 18FDG PET is able to provide unique information in patients with cancer that is not available with other current techniques, leading to changes in patient management that are not only cost effective but result in improved outcome.
In addition to confirming cost effectiveness in other oncological and non-oncological applications, the next area where the use of PET must be more extensively evaluated, and where there are large potential benefits to patients, is in the early evaluation of cancer treatments, not only with 18FDG but also with novel tracers specific to other aspects of tumour biology.
Received for publication November 14, 2000. Accepted for publication January 21, 2001.
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TopIntroductionReferences |
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