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Annotation POSITRON EMISSION TOMOGRAPHY AND THE ORTHOPAEDIC SURGEON M. A. Smith, M. J. O’Doherty Orthopaedic surgeons have embraced a variety of imaging techniques over the last decade. CT and MRI have improved the anatomical definition of abnormalities and radionucleide imaging the functional definition of disease. Progress continues in trying to define the sites of disease and the nature of its activity using magnetic resonance 1-3 spectroscopy (MRS) and positron emission tomography 4-8 (PET). It was therefore surprising that a recent paper by 9 Cheng and Thompson made no mention of PET. PET allows the visualisation of the metabolic activity of disease. In orthopaedic surgery it is of most help in the diagnosis of malignant tumours and their recurrence, the staging of tumours and the monitoring of their response to therapy, and in the diagnosis of osteomyelitis. The positron-emitting tracers may be used to define 18 glucose metabolism ( F-fluorodeoxyglucose (FDG)), ami11 11 no-acid uptake ( C-methionine; C-tyrosine), DNA turno18 ver ( F-fluoro methyl thymidine (FLT)), tissue hypoxia 18 18 ( F-fluoromisonidazole) and possible bone turnover ( Ffluoride). Tumours and infection show increased uptake of FDG which can therefore be used in both circumstances. Primary malignant tumours presenting to the orthopaedic surgeon are either of bone or the connective tissues, i.e., sarcoma of bone or soft tissue. These are rare and should be dealt with at centres where there is a multidisciplinary team 10 available to provide the necessary expertise which should include imaging facilities to give accurate localisation and characterisation of the primary tumour. FDG imaging of soft-tissue sarcomas can distinguish high-grade from low4,8,11 grade tumours and benign lesions, although the separation of low-grade from benign lesions is not possible. Metabolic imaging with FDG combined with MRI may be useful in directing the surgeon to the most malignant area M. A. Smith, FRCS, Consultant Orthopaedic Surgeon St Thomas’ Soft Tissue Tumour Unit, Department of Orthopaedics, Guy’s Hospital, St Thomas’ Street, London SE1 9RT, UK. M. J. O’Doherty, Senior Lecturer in Radiological Sciences Guy’s and St Thomas’ Clinical PET Centre, St Thomas’ Hospital, Lambeth Palace Road, London SE1 7EH, UK. ©2000 British Editorial Society of Bone and Joint Surgery 0301-620X/00/310819 $2.00 J Bone Joint Surg [Br] 2000;82-B:324-5.. 324 within a large heterogeneous mass. Biopsy should be undertaken in conjunction with, or preferably by, the orthopaedic surgeon who will eventually carry out the definitive 10 procedure. A combination of imaging techniques may be used, first to define the most abnormal site by MRI/CT with FDG PET and then to carry out the biopsy using CT for guidance. The biopsy is a crucial step in the management of soft-tissue and bone sarcomas, particularly with the increasing use of adjuvant therapies before definitive surgery. Any information which helps the surgeon to take the most appropriate sample of the tissue is essential in order to make an accurate diagnosis and to prevent 12 complications. FDG PET is useful in the localisation of distant and multisystem disease in patients with soft-tissue sarcomas or sarcomas of bone. The localisation of metastases from softtissue sarcoma in the lung, however, is not as sensitive as 7 that with CT, although metastases from osteosarcoma are 13 readily visualised. The combination of an initial wholebody FDG PET scan with a local scan of the tumour, CT of the chest and MRI of the primary lesion is probably the optimum initial appraisal to provide more precise evaluation of the primary tumour and lead to more accurate staging. Definition of the primary tumour with a number of 14 radiotracers will allow the determination of blood flow, 11 15 the turnover of DNA using C-thymidine or possibly 16,17 FLT, the turnover of amino acids, hypoxia of the tumour and the glucose metabolism. This will enable metabolic staging of the tumour to be done which may have a predictive value equal to or surpassing histological techniques, although this is as yet unproven. These tracers will also provide information to direct and monitor the response 6,13 to neoadjuvant therapy, and to allow the assessment of its delivery. An interesting study assessing the value of neoadjuvant therapy before and after treatment in osteosarcomas has shown that the FDG response after such regimes has helped to identify those tumours which have had a suitable response before operation, and may therefore 13 influence further surgical procedures. Although the best strategies for imaging still need to be established for these 11 various groups of tumours, multicentre trials should include PET in order to confirm its role. Another area of potential use of FDG PET is in the THE JOURNAL OF BONE AND JOINT SURGERY ANNOTATION 18 localisation of infection within bone. Sugawara et al have shown in a small number of patients that FDG accumulated in areas affected with chronic osteomyelitis, although one false-negative result was noted among six patients. Guhl19 mann et al explored the use of FDG PET in 51 patients with suspected osteomyelitis, of whom 28 had the infection and 23 did not. This study compared the use of bone scanning and antigranulocyte antibody imaging with FDG PET, and showed that FDG had an accuracy in the peripheral skeleton of 96% and in the central skeleton of approximately 96%, compared with 89% and 76%, respectively, for the antigranulocyte antibody imaging. The use of FDG has the potential advantage of a single-step procedure with imaging one hour after the injection, rapid loss of radioactivity from the patient and a radiation dose comparable to the leucocyte imaging techniques. The advent of dualcoincidence PET imaging or C-PET will make the use of these techniques practicable in conventional Departments of Nuclear Medicine. The introduction of expensive technology must be carefully assessed. Savings in cost seem to be the most important factor by which management issues are judged, but the issues of quality and cost-effectiveness should be the major concern in the care of patients. PET has been shown to be cost-effective in the management of lung cancer by reducing morbidity from unnecessary operative intervention and allowing better selection of patients for definitive sur20,21 Although PET has been used clinically for only gery. ten years it is becoming increasingly valuable to the orthopaedic surgeon. FDG PET should be used in the assessment of tumours and included in prospective studies of their surgical management and their response to neoadjuvant therapies. The potential use in infection is that no cell labelling is required, rapid imaging is achievable and the radiation dose is reasonable compared with that of leucocyte imaging. New techniques in medicine are often slow to be used, but the clinical application of PET has come of age. Further work needs to be undertaken to allow its optimum utilisation. References 1. Shinkwin MA, Lenkinski RE, Daly JM, et al. Integrated magnetic resonance imaging and phosphorus spectroscopy of soft tissue tumors. Cancer 1991;67:1849-58. 2. Ross B, Helsper JT, Cox IJ, et al. Osteosarcoma and other neoplasms of bone: magnetic resonance spectroscopy to monitor therapy. Arch Surg 1987;122:1464-9. VOL. 82-B, NO. 3, APRIL 2000 325 3. Li CW, Kuesel AC, Padavic-Shaller KA, et al. Metabolic characterization of human soft tissue sarcomas in vivo and in vitro using proton-decoupled phosphorus magnetic resonance spectroscopy. Cancer Res 1996;56:2964-72. 4. Eary JF, Conrad EU, Bruckner JD, et al. Quantitative [F-18]fluorodeoxyglucose positron emission tomography in pretreatment and grading of sarcoma. Clin Cancer Res 1998;4:1215-20. 5. Kole AC, Nieweg OE, van Ginkel RJ, et al. Detection of local recurrence of soft-tissue sarcoma with positron emission tomography using [18F]fluorodeoxyglucose. Ann Surg Oncol 1997;4:57-63. 6. Jones DN, McCowage GB, Sostman HD, et al. Monitoring of neoadjuvant therapy response of soft-tissue and musculoskeletal sarcoma using fluorine-18-FDG PET. J Nucl Med 1996;37:1438-44. 7. Lucas JD, O’Doherty MJ, Wong JC, et al. Evaluation of fluorodeoxyglucose positron emission tomography in the management of soft-tissue sarcomas. J Bone Joint Surg [Br] 1998;80-B:441-7. 8. Schulte M, Brecht-Krauss D, Heymer B, et al. Fluorodeoxyglucose positron emission tomography of soft tissue tumours: is a noninvasive determination of biological activity possible? Eur J Nucl Med 1999;26:599-605. 9. Cheng EY, Thompson RC. New developments in the staging and imaging of soft-tissue sarcomas. J Bone Joint Surg [Am] 1999;81-A:882-92. 10. Springfield DS, Rosenberg A. Biopsy: complicated and risky. J Bone Joint Surg [Am] 1996;78-A:639-43. 18 11. Lodge MA, Lucas JD, Marsden PK, et al. A PET study of FDG uptake in soft tissue masses. Eur J Nucl Med 1988;26:22-30. 12. Mankin HJ, Lange TA, Spanier SS. The hazards of biopsy in patients with malignant primary bone and soft tissue tumors. J Bone Joint Surg [Am] 1982;64-A:1121-7. 13. Schulte M, Brecht-Krauss D, Werner M, et al. Evaluation of neoadjuvant therapy response of osteogenic sarcoma using FDG PET. J Nucl Med 1999;40:1637-43. 14. Schwarzbach M, Willeke F, Dimitrakopoulou-Strauss A, et al. Functional imaging and detection of local recurrence in soft tissue sarcomas by positron emission tomography. Anticancer Res 1999;19:1343-9. 15. Shields AF, Mankoff DA, Link JM, et al. Carbon-11-thymidine and FDG to measure therapy response. J Nucl Med 1998;39:1757-62. 16. van Ginkel RJ, Kole AC, Nieweg OE, et al. L-[1-11C]-tyrosine PET to evaluate response to hyperthermic isolated limb perfusion for locally advanced soft-tissue sarcoma and skin cancer. J Nucl Med 1999;40:262-7. 17. Plaat B, Kole A, Mastik M, et al. Protein synthesis rate measured with L-[1-11C]tyrosine positron emission tomography correlates with mitotic activity and M1B-1 antibody-detected proliferation in human soft tissue sarcomas. Eur J Nucl Med 1999;26:328-32. 18. Sugawara Y, Braun DK, Kison PV, et al. Rapid detection of human infections with fluorine-18 fluorodeoxyglucose and positron emission tomography: preliminary results. Eur J Nucl Med 1998;25:1238-43. 19. Guhlmann A, Brecht-Krauss D, Suger G, et al. Fluorine-18-FDG PET and technetium-99m antigranulocyte antibody scintigraphy in chronic osteomyelitis. J Nucl Med 1998;39:2145-52. 20. Gambhir SS, Hoh CK, Phelps ME, Madar I, Maddahi J. Decision tree sensitivity analysis for cost-effectiveness of FDG-PET in the staging and management of non-small-cell lung carcinoma. J Nucl Med 1996;37:1428-36. 21. Gambhir SS, Shepherd JE, Shah BD, et al. Analytical decision model for the cost-effective management of solitary pulmonary nodules. J Clin Oncol 1998;16:2113-25.