Positron emission tomography in oncology

Transcription

1 British Medical Bulletin Advance Access published December 14, 2006 Positron emission tomography in oncology Jonathan D. Berry and Gary J. R. Cook * Department of Radiology and * Department of Nuclear Medicine and PET, Royal Marsden Hospital, Downs Road, Sutton, Surrey SM2 5PT, UK Introduction Accepted: November 1, 2006 *Correspondence to: Dr G. J. R. Cook, Department of Nuclear Medicine and PET, Royal Marsden Hospital, Downs Road, Sutton, Surrey SM2 5PT, UK. gcook@icr.ac.uk Increasing access to positron emission tomography-computed tomography (PET-CT) has resulted in a shift towards functional imaging, being the primary tool in the assessment of viable tumour in oncology patients. In this review, we discuss the basic principles of this evolving technology and the radio-isotopes it employs. The main clinical applications of PET-CT are reviewed and some of the limitations of the technique are highlighted. Finally, we offer insight into possible future developments and how these modify current practice. Staging of tumours and assessment of their response to therapy have traditionally been based around assessment of structural change. The techniques of computed tomography (CT), magnetic resonance, ultrasound and plain film radiography are all employed, either alone or in combination, to evaluate structural abnormality. The most frequently used technique in terms of whole-body staging is currently CT. 1 Avarietyof protocols have been developed that aim to standardize the interpretation of oncological CT imaging. A key feature of almost all such protocols is that it is the absolute size that of the tumour, lymph nodes or metastasis that is used to decide the presence or absence of malignancy or the change in size that is used to assess the degree of response to treatment. Of these protocols, the Response Criteria In Solid Tumours (RECIST) is one of the protocols more commonly used. RECIST takes into consideration the summation of uni-lateral measurements of suspected sites of disease. The size of a lesion or, in the case of treatment response, the percentage change in size of a lesion since the previous scan dictates whether a CT is reported as showing active disease, response to treatment or progression of disease. Unfortunately, such methods are subject to considerable inter- and intra-observer variation 2 and fail to differentiate post-therapy residual structural abnormality from viable malignancy. Functional imaging, in particular, positron emission tomography (PET), aims to overcome these weaknesses. British Medical Bulletin 2006; 1 16 DOI: /bmb/ldl013 & The Author Published by Oxford University Press. All rights reserved. For permissions, please journals.permissions@oupjournals.org

2 J. D. Berry and G. J. R. Cook PET history and principles The first recorded medical use of positrons was in 1951 when a simple sodium iodide detector probe was used to localize a brain tumour. 3 Much of the initial work using PET centred on neuropsychiatric and cardiac research. Only in 1997 when FDA approval for the use of 18 F-fluorodeoxyglucose ( 18 FDG) as a radiopharmaceutical was granted and subsequently when reimbursement was approved, did whole-body scanning for clinical applications start to take off. Traditionally, PET and CT have been seen as complementary technologies, which were used sequentially in the diagnosis of cancer. Such an approach required mental mapping of abnormalities seen on PET to the anatomical structures seen on CT. Software for retrospective fusion of PET and CT images is available. However, outside the brain, precise mapping is problematic due to the large potential variability in, for example, patient position between the two scans. These problems were resolved with the introduction of the PET CT scanner. The first such scanner began to operate in 1998 and the first clinical machine began to operate in March An appreciation of the importance of this advance was rapidly gained and by 2004, PET CT was reported to be the fastest growing imaging modality with up to 1000 systems installed worldwide in 2004 alone. 4 In addition to limiting the spatial and temporal differences between the two sets of images, PET CT has a number of other advantages over either PET or CT alone. The most significant of these is the use of the CT data (modified to allow for the difference in photon energy between CT and PET) for attenuation correction which improves image quality and is essential for quantitative accuracy of PET. Using this technique as opposed to the conventional rod-source attenuation correction on PET-only systems allows scan times to be reduced by 25 30%. 4 Typically, a combined whole PET CT scan is now completed in 30 min and PET-reconstructed image resolution is of the order of 5 7 mm. In addition to simply documenting the presence or absence of metabolically active tissue, there is also the potential for measurement of metabolic activity using PET. Such a measurement would be particularly appealing in the practice of oncology when assessing, for example, response of a tumour to treatment. 5 The most widely used technique involves calculating the ratio of tumour activity concentration to that in the remainder of the body and is termed the standardized uptake value (SUV). It is recognized that SUV is far from perfect. 6 There are several variables that can affect SUV, including time between injection and scanning, plasma glucose and patient body size (both habitus and body composition). Of particular relevance in Page 2 of 16 British Medical Bulletin 2006

3 PET in oncology oncology patients are alterations in blood glucose and body size. Some centres advocate the use of SUV corrected for lean body mass 7 and blood glucose level on the basis that it is common for oncology patients to suffer weight loss either as a result of their disease or treatment and chemotherapeutic agents may alter blood glucose levels over time (raised blood glucose has been shown to reduce SUV). Radiopharmaceuticals Functional imaging using PET may take many forms. Although initial experimental laboratory work used a variety of radioisotopes, for example, 14 C labelled deoxyglucose, 8 the most widely used imaging technique in clinical practice today is 18 FDG PET. 18 FDG acts as a glucose analogue. Following its intravenous (IV) injection, 18 FDG localizes to sites where there is active metabolism and increased glucose uptake. Malignant neoplasms have, for many years, been known to be highly metabolically active 9 with several tumour types overexpressing the GLUT-1 membrane glucose transporter protein. Consequently, many malignancies display avid uptake of 18 FDG. Once within the cell, 18 FDG undergoes phosphorylation by hexokinase to form 18 FDG-6-phosphate. Unlike glucose, 18 FDG-6-phosphate is subsequently subjected to minimal enzymatic reactions and as a result will accumulate within the cell at a rate proportional to glycolysis. Other factors that modulate the amount of 18 FDG uptake include the number of viable tumour cells and blood flow to and within the tumour. Enhanced blood flow is of particular importance since without this, a tumour will rapidly outgrow its blood supply and necrosis will occur. Much interest has, therefore, been centred on the subject of angiogenesis. Although primarily a research tool, PET may be employed to assess tumour angiogenesis. Two approaches have been used to achieve this. The first measures the accumulation of a freely diffusible tracer ( 15 oxygen water) to indirectly assess blood flow. The second detects the markers of angiogenesis (such a vascular endothelial growth factor receptor) using isotope-labelled monoclonal antibodies directed against the target detected with PET. 10 Recently, interest has grown in the potential for use of a variety of radiopharmaceuticals other than 18 FDG in oncological imaging. For example, research has demonstrated the accumulation of derivatives of choline and 11 C-acetate in prostate cancer. Although 11 C-acetate is unlikely to be of widespread clinical use due its short half-life (20 min), 18 F-based (half-life 110 min) choline compounds may prove to be of use and currently being investigated. 11 Other examples include the use of 18 F-DOPA in the investigation of neuro-endocrine tumours, British Medical Bulletin 2006 Page 3 of 16

4 J. D. Berry and G. J. R. Cook 18 F-thymidine as a marker of cellular proliferation and labelled antibodies targeted against specific tumour proteins. 4 As yet, all these remain as research tools, with 18 FDG PET CT being used for the bulk of clinical work. PET CT image interpretation and artefacts Normal uptake An appreciation of sites of normal physiological uptake together with an understanding of potential artefacts and limitations 12 must be gained in order to accurately interpret either PET or PET CT scans. There are many sites of relatively high metabolic uptake in the body which must not be misinterpreted as pathological uptake of tracer. 13,14 As the brain primary substrate for metabolism is glucose, there is predictably high 18 FDG within the cortical tissue, brain s stem and basal ganglia. This limits the sensitivity of 18 FDG PET CT for the detection of intra-axial malignant disease. The liver spleen and bone marrow demonstrate homogeneous lowgrade uptake, but this does not usually obscure the presence of avid malignant processes within these organs. Myocardial uptake is variable, although, in general, the left ventricular myocardium will be greater than the background blood pool. Moderate uptake may be seen in normal-sized lymphoid tissue in Waldeyer s ring and thymic tissue of children. In addition, postchemotherapy thymic rebound may occasionally be seen in children and young adults. Pre-menopausal women may display moderate uptake in glandular breast tissue, which can become marked during lactation. Cyclical ovarian and uterine activity may also be seen. Uptake within the gastro-intestinal tract ranges from almost undetectable to diffuse high uptake. Diffuse low-grade uptake within the oesophagus is most commonly due to oesophagitis. Similarly, gastritis due to Helicobacter pylori infection within the stomach may result in diffuse uptake within the gastric mucosa, although some uptake is normally seen. Minimal uptake is usually seen within the small bowel. In contrast, the large bowel and, in particular, the caecum may display avid uptake. The cause of this avid uptake is likely to be multi-factorial and includes mucosal activity, regional lymphatics and bacterial activity within the lumen of the bowel. Page 4 of 16 British Medical Bulletin 2006

5 PET in oncology Benign causes of 18 FDG uptake 18 FDG PET CT has limited sensitivity for detection of tumours within the urinary tract since 18 FDG is, unlike glucose, subject to renal excretion. Consequently, the renal collecting systems, ureters and bladder frequently show high activity, and detecting a renal or bladder tumour against this background activity is difficult. Some advocate catheterization of patients and washout of the bladder to enhance the detection of pelvic malignancy; however, generally, if the patient is well hydrated and the 18 FDG within the bladder is therefore diluted, this is not necessary. Testicular activity is variable and tends to be higher in younger patients. Foci of active brown fat are occasionally seen in children and young adults and are typically symmetrical and located around the lower neck and scapulae. Brown fat is known to be highly metabolically active and is responsible for thermogenesis and, consequently, is often seen as areas of avid tracer uptake on PET CT, particularly in cold weather (Fig. 1). Following the injection of 18 FDG, patient movement and speech should be limited in order to minimize skeletal muscle uptake, which may otherwise be misinterpreted as abnormal uptake. In addition to physiological uptake, there are numerous benign causes of uptake that may mimic malignancy. 15 Typically, these benign causes are sites of inflammation or infection and include the following. Osteoblastic activity together with granulation associated with bone healing, whether it be of iatrogenic or traumatic origin, results in an elevated 18 FDG uptake in the acute or subacute phase of healing. In the case of rib fractures or a healing sternotomy, the linear nature of the uptake makes delineation from malignant causes relatively easy. Conversely, an isolated fracture with florid callus may be very difficult to differentiate. Similarly, degenerative or inflammatory arthritis can result in increased tracer uptake. This may be markedly asymmetrical, e.g. the acromioclavicular joint on the side of the dominant hand, but is rarely mistaken for malignancy. Detection of infiltrated lymph nodes is of great importance to cancer staging and therefore treatment. The absolute size of a node gives some indication of the likelihood of malignant infiltration as opposed to reactive enlargement; however, there is inevitably a grey area of overlap between the two groups. A major advantage of PET CT is its ability to detect malignant infiltration in nodes that are not size British Medical Bulletin 2006 Page 5 of 16

6 J. D. Berry and G. J. R. Cook Fig. 1 (A) Coronal PET images reveal avid bilateral FDG uptake both at the anterior and at the posterior aspects of the neck. (B) CT and fused PET CT images demonstrate this FDG uptake to be within the sterno-cleidomastoid muscles (due to patient movement) and metabolically active brown fat. Page 6 of 16 British Medical Bulletin 2006

7 PET in oncology Problems specific to PET CT significant (Fig. 2). Unfortunately, granulomatous conditions such as tuberculosis or sarcoidosis can cause increased tracer uptake. 16 In addition, recent infection, surgery or extravasation of tracer at the injection site may all cause varying degrees of increased tracer uptake in draining lymph nodes. Sites of localized soft tissue infection or inflammation/granulation may result in tracer uptake. Examples include abscesses, stoma sites and pancreatitis. 17 Distinguishing such abnormalities from malignant deposits can be problematic but is often resolved through reference to the CT component of the image. Although a single machine, the CT and PET components of a PET CT examination are acquired separately. Modern multi-slice CT potentially allows whole-body scanning within a single breathhold. In contrast, a whole-body PET requires 20 min to acquire and is, therefore, subject to breathing movement artefact. Mis-registration between the two sets of images may therefore occur, particularly in the thorax and around the diaphragm. Some advocate acquiring the CT data during normal expiration. 12 However, in practice, patients may find this difficult to achieve. Such mis-registration is a factor that limits the sensitivity of PET CT in the detection of focal lung nodules. It is a common belief among many that PET CT is not appropriate for the assessment of subcentimetre pulmonary nodules due to the poorer spatial resolution of PET when compared with CT and the movement of nodules during the PET image acquisition. Although this is in part true, in reality, if a nodule is highly 18 FDG avid, it is likely to be visualized even if it is,1 cm in diameter. However, on average, the sensitivity for subcentimetre metastases has been reported to be,80 or,40% when 5 7 mm. 18 Using the CT data for attenuation correction may lead to artefactual overestimation of tracer uptake. This typically occurs when highly attenuating materials, e.g. prosthetic metal devices or high density oral contrast, are present. PET CT is commonly performed in the absence of IV contrast. Although some have suggested that IV contrast may improve diagnostic accuracy, it is likely that a concentrated intravascular bolus of contrast (which will have dissipated by the time the PET component is acquired) would lead to artefactual activity in the attenuation corrected image. 19 This is unlikely to lead to misinterpretation; however, newer reconstruction algorithms can overcome this artefact. British Medical Bulletin 2006 Page 7 of 16

8 J. D. Berry and G. J. R. Cook Fig. 2 Contrast-enhanced staging CT revealed a patient with breast cancer to have a solitary left upper lobe pulmonary metastasis. Prior to resection of the pulmonary metastasis, PET CT was performed. Coronal PET images (A) reveal there to be multiple sites of abnormal FDG uptake. Axial fused PET CT images confirm these to include avid axillary and mediastinal nodes (B) (considered borderline significance by size criteria on the staging CT) together with disease within the liver (C) and bones (D). Page 8 of 16 British Medical Bulletin 2006

9 PET in oncology Common uses of PET CT in current oncology practice Differing arrangements for reimbursement are a factor for differences in practice between regions. The following are common uses of PET CT in current practice in the UK. Thoracic malignancy PET CT is now integral to the evaluation of pulmonary nodules, staging of lung cancer, planning of therapy and diagnosis of recurrent disease with its use being advocated by the British Thoracic Society. 20 Furthermore, PET CT is proved to be better than PET alone, CT alone or PET and CT performed separately and viewed together. Indeed, PET CT provided additional information in 41% of cases reviewed. 21 Examples of such information include evaluation of chest wall invasion by a tumour which is difficult with PET alone due to the limited anatomical accuracy but can be more easily evaluated with combined PET and CT. One area in which PET CT is likely to be of benefit over PET alone is in the detection of small pulmonary nodules, although at present the data to support this are lacking. In primary lung malignancies where there is associated bulky mediastinal lymph node enlargement, the nodal staging (N-staging) component of tumour, nodes, metastasis (TNM) staging is rarely problematic. Difficulty arises when there are nodes that are not significant by CT criteria but which if found to be infiltrated with malignancy would significantly alter the course of treatment (usually affecting whether curative surgery should be contemplated or not). This is particularly true of small hilar nodes since infiltration of these nodes is pivotal in deciding whether nodal status is N1 or N2. PET has proved to be highly effective in such cases with a specificity of 93% and a sensitivity of 88% for the delineation of infiltration of mediastinal nodes. 22 Tumour recurrence within the thorax in the context of distorted anatomy following surgery and radiotherapy can be difficult to detect. PET CT may be extremely useful in such a setting since viable tumour can be appreciated as separate from the surrounding post-therapy changes seen on the CT. 23 Although clearly a useful tool for the assessment of malignancy in the thorax, PET CT does have limitations. Examples include poor delineation of bronchioalveolar cell carcinomas and malignant pleural effusions. Its use in the evaluation of thoracic malignancies other than primary lung cancer remains under evaluation. One area of particular interest is the assessment of malignant pleural mesothelioma in which British Medical Bulletin 2006 Page 9 of 16

10 J. D. Berry and G. J. R. Cook PET CT has been shown to be of benefit in the assessment of chest wall invasion and nodal involvement. 24 Gastro-intestinal malignancy Colorectal malignancy is second only to lung cancer in terms of malignancy-related deaths in Western countries. Although PET CT has not yet been fully evaluated as a means of primary diagnosis, PET is of proven benefit in the staging and subsequent re-staging of colorectal carcinomas. 25 A recent study, 26 has shown PET to be sensitive for the detection of the primary colonic tumour (96%) and distant metastases (78%), but to have relatively low sensitivity for abdominal and pelvic lymph node staging (29%). It is, however, important to remember that PET is unlikely to be used in isolation for the staging of colorectal malignancy. More likely is that there will be multiple modalities used in the disease staging. Current common practice is to use magnetic resonance imaging (MRI) for local tumour staging and pelvic lymph node staging of rectal tumours and CT or PET CT to detect disseminated malignancy from a colorectal tumour. In addition, MRI and ultrasound (including micro-bubble contrast-enhanced ultrasound) may be used to characterize focal liver lesions. Even with the use of pelvic MR, whole-body CT, tumour markers and clinical examination, detection of recurrent colorectal malignancy is often problematic. This is commonly due to the difficulty in differentiating recurrent disease from post-surgical change. Several studies have demonstrated PET to be helpful in detecting recurrent disease. 4 Furthermore, when compared with PET alone, PET CT improves diagnostic accuracy 27 (likely due to the enhanced localization of lesions that CT component allows). Gastro-intestinal stromal tumours (GISTs) are mesenchymal tumours that arise most commonly from the stomach or small bowel. GISTs demonstrate heterogeneous 18 FDG uptake between patients and even between different tumour sites within the same patients. Consequently, the role of PET CT in the assessment of GIST was initially uncertain. This view has in part been altered by recent evidence proving the benefit of PET CT over contrast-enhanced CT in the assessment of response of GIST to the tyrosine kinase inhibitor imatinib mesylate. 28 Lymphoma Given the curative intent in a high percentage of lymphoma patients, accurate diagnosis, staging and follow-up in this group of patients is Page 10 of 16 British Medical Bulletin 2006

11 PET in oncology Head and neck malignancy essential. Current practice for staging of lymphoma will usually include contrast-enhanced CT from base of skull to upper thighs. Almost every healthy individual will have some lymph nodes commonly in the head and neck, axillae and inguinal regions and it can be difficult to differentiate on the basis of size alone that which of these nodes are infiltrated with disease. Since this decision is critical in determining whether local or systemic therapy will be employed, accurate assessment is of paramount importance. Fortunately, both Hodgkin and non-hodgkin lymphomas will usually demonstrate avid 18 FDG uptake at the time of diagnosis. 29 Studies have indicated PET CT to be more sensitive and specific in the evaluation of nodal and extra-nodal disease in patients with lymphoma. 30 In particular, the sensitivity of detection of extra-nodal disease is improved by the use of PET CT as opposed to CT alone (88 and 50%, respectively). Following treatment, up to 64% of patients display some residual abnormality, and differentiating fibrosis and necrosis from viable tumour cells is notoriously difficult. FDG PET CT is one of the most accurate non-invasive methods for differentiating viable from non-viable residual masses. PET CT also plays an important role in the evaluation of response to treatment. Patients in whom there is no detectable FDG uptake post-treatment generally have a better prognosis than those in whom there is residual uptake. 31 Despite the use of a variety of imaging techniques, including contrast-enhanced MR, CT and ultrasound, the accurate staging and detection of disease recurrence in head and neck cancers remain problematic. The limitations of these structural imaging techniques in the head and neck are that the anatomy is complex and when distorted by either tumour or treatment, defining viable disease can be difficult. Furthermore, the large number of physiological or reactive nodes around the head and neck can result in equivocal reports. An additional problem for CT and MR interpretation is the widespread use of metallic dental amalgam, resulting in streak and susceptibility artefact, respectively. PET has been shown to improve accuracy of staging of head and neck malignancy when compared with CT or MR 32 and PET CT is more accurate than PET or CT alone. 33 In addition to staging of head and neck cancers, PET CT is finding increased use for the detection of occult sites of primary malignancy in the head and neck. Owing to several sites of normal physiological uptake, e.g. salivary glands, and the potential for artefact, e.g. muscle uptake from talking or chewing, care must be employed when reporting PET CT of the head and neck. British Medical Bulletin 2006 Page 11 of 16

12 J. D. Berry and G. J. R. Cook Breast cancer Pancreatic and hepatic malignancy Thyroid malignancy Uptake of FDG in primary breast cancer is variable, with some showing very little uptake and others being avid. Even tumours of the same histological type may differ in uptake of FDG. Furthermore, PET sensitivity for the detection of small lesions within the breast is likely to be limited. Consequently, PET CT is not generally used in the assessment of the primary breast mass and axillary nodes. Where it is of use is in the assessment of systemic metastatic disease, detection of disease recurrence and the monitoring of therapy. One recent study has demonstrated PET to have a sensitivity of 89% and a specificity of 88% for the detection of disease recurrence with 30% of patients originally thought only to have local disease recurrence found to have more distant disease on PET. 34 Current practice is to use ultrasound, contrast-enhanced CT or contrastenhanced MR for the detection of focal liver lesions and then, if necessary, to use triple phase CT, dynamic MR or possibly contrast-enhanced ultrasound to further characterize a lesion. Such an approach is generally robust and PET CT has a limited role to play in the assessment of a primary hepatic malignancy. Where PET CT is in of use is the detection of disseminated malignancy from a hepatic primary since this is likely to significantly modify treatment options, for example, if segmental resection or orthotic liver transplantation is being considered. Detection of primary pancreatic malignancy in its early stage is problematic, regardless of the imaging modality used. Currently, contrast-enhanced multi-slice CT is the primary technique for the assessment of a suspected pancreatic tumour. PET has been shown to be superior to structural imaging techniques for the detection of distant metastasis and local recurrence following treatment 35. Radioiodine scintigraphy is the main modality used in the assessment of thyroid malignancy. Dedifferentiation of a thyroid malignancy may result in failure of the tumour cells to accumulate iodine and consequently inability to image or treat the tumour with radioiodine. PET plays a role in such cases and has been shown to be up to 94% sensitive in the detection of recurrent local tumour or metastasis. 36 PET CT has advantages over PET alone when imaging neck in search of recurrent thyroid disease due to the added anatomical information making it easier to differentiate recurrent tumour from, for example, muscles around the vocal cords. Page 12 of 16 British Medical Bulletin 2006

13 PET in oncology Gynaecological malignancy Melanoma Unknown primary malignancy Ovarian cancer and cervical cancer together are a major cause of mortality and morbidity in the female population. Although PET CT is not commonly used in the assessment of these malignancies, a recent small study suggests that it may have a role to play 37 particularly in the detection of disseminated disease when potentially curative surgery is being considered (Fig. 3). Of particular note is the improved accuracy of detection of pelvic lymph nodes in cervical carcinoma with PET relative to CT since this is likely to modify therapy and serve as a predictor of survival. 38 Melanoma is characterized by its avidity for FDG and its ability to metastasize to unusual sites. Melanoma is potentially curable by surgery if the disease is at an early stage in its growth. Although there are no data to suggest that PET is of benefit in the initial diagnosis of melanoma, it is of proven benefit in the subsequent staging. PET is proven to be more sensitive than CT in the detection of metastasis within the skin, abdomen and lymph nodes, with CT more sensitive than PET in the detection of pulmonary lesions. 39 It is, therefore, likely that PET CT will be particularly effective in the staging of melanoma. Between 5 and 10% of all patients diagnosed with malignancy have no known primary at the time of diagnosis. Establishing the site and histological type of a primary tumour is important because it facilitates directed therapy and improves survival. The case for the use of PET CT to detect a primary tumour in patients with metastasis of unknown origin would seem compelling. Unfortunately, evidence suggests that PET CT is not significantly better than PET, CT or CT and PET read together (sensitivities of 33, 24, 18 and 29%, respectively). 40 Even though the advantage of PET CT is small, it is becoming established as the investigation of choice in these difficult cases. Conclusion In a short space of time, PET CT has established itself as an essential component in the assessment of malignancy. There is little doubt that as understanding of PET CT grows among the medical community as a whole, indications for PET CT will grow. Furthermore, much British Medical Bulletin 2006 Page 13 of 16

14 J. D. Berry and G. J. R. Cook Fig. 3 Patient with known ovarian carcinoma was shown to have a solitary liver metastasis on IV contrast-enhanced CT. PET CT was requested to confirm this to be a solitary site of disease prior to segmental hepatic resection. Coronal PET images (A) show several sites of abnormal FDG uptake in addition to that within the liver. Fused PET CT reveals the presence of both left (B) and right (C) metabolically active para-aortic lymph nodes which were not appreciated on the staging CT. In addition, an avid disease deposit within the left hemi-pelvis (D) was misinterpreted on staging CT as a loop of bowel. Page 14 of 16 British Medical Bulletin 2006

15 PET in oncology research into the potential uses of this technology is currently being undertaken. Of particular interest are developments regarding the application of PET CT in the planning of radiotherapy and intensitymodulated radiotherapy, new radiopharmaceuticals and potential uses of PET CT aside from malignancy. It is likely that as access improves and our understanding grows, PET CT may be the only imaging test required in the initial investigation of oncology patients in some circumstances. References 1 Rankin SC (2003) Assessment of response to therapy using conventional imaging. Eur J Nucl Med Mol Imaging, 30 (Suppl 1), ps56 S64. 2 Erasmus JJ, Gladish GW, Broemeling L et al. (2003) Interobserver and intraobserver variability in measurement of non-small-cell carcinoma lung lesions: implications for assessment of tumor response. J Clin Oncol, 21, Nutt R (2002) 1999 ICP Distinguished Scientist Award. The history of positron emission tomography. Mol Imaging Biol, 4, von Schulthess GK, Steinert HC, Hany TF (2006) Integrated PET/CT: current applications and future directions. Radiology, 238, Hoekstra CJ, Paglianiti I, Hoekstra OS et al. (2000) Monitoring response to therapy in cancer using [18F]-2-fluoro-2-deoxy-D-glucose and positron emission tomography: an overview of different analytical methods. Eur J Nucl Med, 27, Keyes JWJ (1995) SUV: standard uptake or silly useless value. J Nucl Med, 36, Zasadny KR, Wahl RL (1993) Standardized uptake values of normal tissues at PET with 2-[fluorine-18]-fluoro-2-deoxy-D-glucose: variations with body weight and a method for correction. Radiology, 189, Sokoloff L (1981) The deoxyglucose method: theory and practice. Eur Neurol, 20, Warburg O (1956) On the origin of cancer cells. Science, 123, Miller JC, Pien HH, Sahani D, Sorensen AG, Thrall JH (2005) Imaging angiogenesis: applications and potential for drug development. J Natl Cancer Inst, 97, Schmid DT, John H, Zweifel R et al. (2005) Fluorocholine PET/CT in patients with prostate cancer: initial experience. Radiology, 235, Cook GJ, Wegner EA, Fogelman I (2004) Pitfalls and artifacts in 18FDG PET and PET/CT oncologic imaging. Semin Nucl Med, 34, Cook GJ, Fogelman I, Maisey MN (1996) Normal physiological and benign pathological variants of 18-fluoro-2-deoxyglucose positron-emission tomography scanning: potential for error in interpretation. Semin Nucl Med, 26, Cook GJ, Maisey MN, Fogelman I (1999) Normal variants, artefacts and interpretative pitfalls in PET imaging with 18-fluoro-2-deoxyglucose and carbon-11 methionine. Eur J Nucl Med, 26, Shreve PD, Anzai Y, Wahl RL (1999) Pitfalls in oncologic diagnosis with FDG PET imaging: physiologic and benign variants. Radiographics, 19, p61 77, quiz Lewis PJ, Salama A (1994) Uptake of fluorine-18-fluorodeoxyglucose in sarcoidosis. J Nucl Med, 35, Strauss LG (1996) Fluorine-18 deoxyglucose and false-positive results: a major problem in the diagnostics of oncological patients. Eur J Nucl Med, 23, Reinhardt MJ, Wiethoelter N, Matthies A et al. (2006) PET recognition of pulmonary metastases on PET/CT imaging: impact of attenuation-corrected and non-attenuation-corrected PET images. Eur J Nucl Med Mol Imaging, 33, Antoch G, Freudenberg LS, Egelhof T et al. (2002) Focal tracer uptake: a potential artifact in contrast-enhanced dual-modality PET/CT scans. J Nucl Med, 43, British Medical Bulletin 2006 Page 15 of 16

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