Applications of PET/CT in Rheumatology. Role of PET/CT. Annibale Versari, MD Nuclear Medicine PET Center S.Maria Nuova Hospital Reggio Emilia Italy

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1 CME Session Associazione Italiana di Medicina Nucleare ed Imaging Molecolare Applications of PET/CT in Rheumatology Role of PET/CT Annibale Versari, MD Nuclear Medicine PET Center S.Maria Nuova Hospital Reggio Emilia Italy

2 Nuclear Medicine Rheumatology Three-phase bone scan, 67Ga scan, salivary glands scan, PET, PET/CT? Past Present Future

3 PET Clinical Applications 8% 2% 90% Oncology Neurology Cardiology and inflammation?

4 PET in inflammatory disease Why? 18F-FDG accumulates intracellularly mainly in areas of intense glucose metabolism, such as neoplasm infection Zhuang H et al Radiol Clin North Am 2005 inflammatory infiltrate Belhocine T et al Eur J Nucl Med Mol Imaging 2003

5 FDG-PET/CT in Rheumatology Applications Large vessel Vasculitis Arthritis Spondylodiscitis

6 FDG-PET/CT in Rheumatology Applications Large vessel Vasculitis

7 Vasculitis Morphological Imaging Angiography CT. MRI.. Thanks, Dr Stanson

8 ... and PET? In large-vessel vasculitis, FDG accumulates in metabolically active inflammatory cells within the affected vessel walls Shepherd PR et al. N Engl J Med 1999

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10 Large vessel Vasculitis FDG-PET A four-point scale has been proposed to grade the large-vessel FDG uptake Grade 0 = no uptake Grade 1 = minimal uptake (< liver) Grade 2 = moderate uptake (= liver) Grade 3 = marked uptake (> liver) Meller J et al. Eur J Nucl Med Mol Imaging 2003

11 FDG-PET/CT: normal vascular findings

12 Large vessel Vasculitis FDG-PET Interpretation Untreated Patients Grades 2 and 3 are usually considered relatively specific for vasculitis Grade 1 (rarely grade 2) has been observed in segments with atherosclerotic lesions Belhocine T et al Eur J Nucl Med Mol Imaging 2003

13 Large vessel Vasculitis FDG-PET Interpretation Patients in steroid treatment Also Grade 1 is consistent with vasculitis

14 FDG-PET/CT: Vasculitis (grade permission 2 uptake) of author.

15 FDG-PET/CT: Vasculitis (grade 3 uptake)

16 Large vessel Vasculitis MR and FDG PET PET may be more sensitive than MR in early-stage large-vessel vasculitis, Why? Inflammatory cell infiltration (revealed by PET) is likely to precede the development of edema of the vessel wall (depicted by MR). Meller J et al, Eur Radiol 2003

17 Large vessel Vasculitis MRI and FDG-PET

18 Large vessel Vasculitis FDG-PET in Diagnosis Sensitivity % Specificity % Untreated patients with elevated inflammatory markers Meller J et al, J Nucl Med 2007

19 Fever of unknown origin (FUO) Infection Non-infectious inflammatory disease Tumors FDG-PET Contribution to the final diagnosis in 25-69% of pts Meller et al J Nucl Med 2007

20 Large vessel Vasculitis FDG-PET Very helpful in disease activity evaluation Webb M et al. Eur J Nucl Med Mol Imaging 2004 Walter MA et al. Eur J Nucl Med Mol Imaging 2005

21 A.G.L. f Takayasu Arteritis 5 months after treatment withdrawal

22 Large vessel Vasculitis FDG-PET extremely helpful in showing the extent of vascular involvement in the whole body Blockmans D et al. Arthritis Rheum 2006 Bongartz T et al. Curr Opin Rheumatol 2006

23 Large vessel Vasculitis FDG-PET.extent of vascular involvement in the whole body

24 Large vessel Vasculitis FDG-PET Limitations Some arteries, such as the temporal and renal arteries, cannot be visualized (small diameter) PET evaluation: vessels > 4 mm Brodmann M et al. Rheumatology (Oxford) 2004

25 Large vessel Vasculitis FDG-PET PET is both sensitive and specific in the evaluation of disease activity. This data support the use of PET in establishing the response to treatment Meller J et al Eur J Nucl Med Mol Imaging 2003; Hara M et al. J Comput Assist Tomogr 1999 Andrews J et al. Ann Rheum Dis 2004

26 Vasculitis of the large vessels FDG-PET 28 consecutive pts in steroid therapy 23 Takayasu Arteritis 5 Giant Cell Arteritis (38 FDG-PET studies) versus Erythrocyte Sedimentation Rate (ESR) C-reactive protein (CRP) Interleukin-6 (IL-6) Assessment of disease activity according to the Kerr criteria (National Institute of Health criteria) Versari et al, SNM-Washington 2007

27 Vasculitis of the large vessels PET FDG uptake was evaluated using a visual score 0 = no uptake 1 = minimal uptake (< liver) 2 = moderate uptake (= liver) 3 = marked uptake (> liver) in 7 vascular areas and a total score (0-21) was calculated.

28 Vasculitis of the large vessels PET Score and ESR ESR+ ESR PET Score The PET score was significantly higher (p = 0.02) in pts with high ESR The frequency of elevated ESR values was significantly higher (p = 0.049) in presence of vascular FDG uptake ESR+ frequency (%) ESR value FDG uptake+ FDG uptake- ESR values were significantly higher (p=0.026) in pts Slides are not to with be reproduced vascular FDG without uptake

29 Vasculitis of the large vessels PET Score correlation with acute-phase reactants and clinical findings ESR R 0.41 p Significant correlation with ESR and IL-6 but not with CRP IL CRP 0.20 ns Kerr+ Kerr The PET score was significantly higher (p = 0.01) in pts with active disease PET Score

30 Large vessel Vasculitis FDG-PET Limitations Vascular uptake on PET is not specific for vasculitis. significant correlation was found between older age and increased vascular FDG uptake (age-related vessel structural changes, such as atherosclerotic plaques ) Zhang Z et al. BMC Nucl Med 2006

31 Large vessel Vasculitis- Atherosclerosis 18 FDG-PET Differential Diagnosis atherosclerotic and vasculitic lesions may co-exist, particularly in elderly patients some characteristics can help the differential diagnosis Blockmans D. Clin Exp Rheumatol 2003

32 Large vessel Vasculitis- Atherosclerosis 18 FDG-PET Differential Diagnosis vasculitic lesions more intense FDG uptake Kissin EY et al. Curr Opin Rheumatol 2004 involvement of vessels usually spared by atherosclerosis (thoracic vessels) suggests vasculitis different appearance: atherosclerotic plaques vasculitic lesions hot spots smooth and linear Blockmans D. Clin Exp Rheumatol 2003

33 Normal Atherosclerosis Arteritis Pipitone N et al Rheumatology, 2008

34 Chronic Periaortitis 18 FDG-PET Limited data Helpful in evaluation of disease activity establishing the response to treatment, Vaglio A et al Arthritis Rheum 2005 and Lancet 2006 CT residual mass evaluation (often representing metabolically inactive tissue) Vaglio A et al Clin Exp Rheumatol 2005

35 P.M.S. 63 year old female Thoracic aortitis + idiopathic retroperitoneal fibrosis Pipitone N et al Circulation 2008, in press

36 P.M.S. 63 year old female Thoracic aortitis + idiopathic retroperitoneal fibrosis Pipitone N et al Circulation 2008, in press

37 Idiopathic retroperitoneal fibrosis: post steroid therapy CT: residual mass FDG-PET: no uptake

38 Vascular prosthesis infection

39 Aorto-iliac prosthesis infection

40 FDG-PET/CT in Rheumatology Applications Arthritis

41 Normal Patient with RA

42 Positron emission tomography with 18F-FDG in osteoarthritic knee 15 pts with medial-type knee osteoarthritis and 3 healthy subjects conventional radiography, (18)F-FDG PET MRI (18)F-FDG SUV fusion images with MRI (18)F-FDG uptake periarticular lesions intercondylar notch extending along the posterior cruciate ligament, periosteophytic lesions bone marrow. Nakamura H et al, Osteoarthritis Cartilage Jun;15(6):673-81

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44 Hip prosthesis infection

45 Normal findings HIP prosthesis Infection

46 FDG-PET/CT in Rheumatology Applications Spondylodiscitis

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49 Infectious Spondylodiscitis

50 Infectious Spondylodiscitis Response to therapy evaluation

51 Spondylodiscitis in reparative phase

52 FDG-PET in Rheumatology Conclusions Important role in diagnosis and follow-up of large vessel vasculitis (new gold standard of disease activity?) Helpful in fever of unknown origin Interesting perspectives for arthritis and spondylodiscitis but more data are required

53 Thanks for your attention