Whole body F-18 sodium fluoride PET/CT in the detection of bone metastases in patients with known malignancies: A pictorial review

Whole body F-18 sodium fluoride PET/CT in the detection of bone metastases in patients with known malignancies: A pictorial review Poster No.: C-1196 Congress: ECR 2014 Type: Educational Exhibit Authors: J. Murphy, M. O'Keeffe, P. Nicholson, K. James, K. O'Regan; Cork/IE Keywords: Metastases, Comparative studies, PET-CT, Oncology DOI: 10.1594/ecr2014/C-1196 Any information contained in this pdf file is automatically generated from digital material submitted to EPOS by third parties in the form of scientific presentations. References to any names, marks, products, or services of third parties or hypertext links to thirdparty sites or information are provided solely as a convenience to you and do not in any way constitute or imply ECR's endorsement, sponsorship or recommendation of the third party, information, product or service. ECR is not responsible for the content of these pages and does not make any representations regarding the content or accuracy of material in this file. As per copyright regulations, any unauthorised use of the material or parts thereof as well as commercial reproduction or multiple distribution by any traditional or electronically based reproduction/publication method ist strictly prohibited. You agree to defend, indemnify, and hold ECR harmless from and against any and all claims, damages, costs, and expenses, including attorneys' fees, arising from or related to your use of these pages. Please note: Links to movies, ppt slideshows and any other multimedia files are not available in the pdf version of presentations. www.myesr.org Page 1 of 24

Learning objectives Technetium-99m methylene-diphosphonate bone scintigraphy (Tc-99m MDP BS) is currently the imaging method of choice for the diagnosis of bone metastases. It is sensitive, but not specific, and is limited in the assessment of lytic lesions. Studies have shown F-18 sodium fluoride (NaF) positron emission tomography/computed tomography (PET/CT) to have superior specificity and sensitivity than Tc-99m MDP BS in the 1,2 detection of bone metastases. We illustrate our experience with whole body F-18 NaF PET/CT in patients with known or suspected bone metastases. The pharmacodynamics of F-18 NaF and technique, including patient preparation, dose and scanning parameters, are discussed. Our cases illustrate the normal biodistribution of F-18 NaF and demonstrate pitfalls in diagnosis such as benign and inflammatory bone conditions. We demonstrate how F-18 NaF PET/CT can upstage patients with previously negative or equivocal Tc-99m MDP BS, CT and MRI. Background Blau et al first demonstrated the clinical use of F-18 NaF as a bone imaging agent in 3 1962. It was replaced by Tc-99m MDP with the introduction of the Anger camera. In recent years, with the expanding use of PET/CT and the commerical availability of F-18 PET tracers, there is renewed interest in F-18 NaF as a bone imaging agent. Figure 1 illustrates examples of both F-18 NaF and Tc-99m MDP in clinical use. Page 2 of 24

Fig. 1: Example of F-18 NaF PET/CT (left) and Tc-99m MDP BS (right) Following intravenous injection, F-18 NaF is rapidly cleared from plasma, accumulated in bone and excreted through glomerular filtration. Fluorides pass from plasma, through the extracellular fluid space, into the bound water shell of bone surface by passive diffusion. Skeletal accumulation of fluoride is proportional to regional blood flow and rate of bone turnover. It is considered localised to bone once it has entered the bound water shell of bone surface. Owing to rapid renal clearance and fast bone accumulation rate, a high bone-soft tissue contrast can be obtained 1 hour following injection of F-18 NaF compared with 3-6 hours for MDP. Tc-99m MDP BS is currently the imaging method of choice for the diagnosis of bone metastases. It is sensitive but not specific and limited in the assessment of lytic lesions. Although CT provides good anatomic resolution, soft tissue contrast and detailed morphology, significant cortical destruction is needed for detection of bone metastases. 4 Owing to this, the sensitivity of CT in detecting early bone metastases is relatively low. Page 3 of 24

Hybrid techniques such as PET/CT allow the acquisition of both functional and anatomical studies in one combined examination. Fused images allow the characterisation of a lesion according to its metabolic activity and morphologic appearance. The two tracers currently available for bone imaging in PET/CT are F-18 NaF and F-18 fluorodeoxyglucose (FDG). Studies have shown F-18 NaF PET/CT to have superior specificity, sensitivity and diagnostic accuracy than Tc-99m MDP BS, Tc-99m MDP SPECT and F-18 FDG PET 1,2,5 in the detection of bone metastases. There are limited prospective studies directly comparing F-18 NaF PET/CT and F-18 FDG PET/CT. However F-18 FDG PET is limited 6-8 in detecting sclerotic bone metastases. To date, there are no defined criteria for appropriate use F-18 NaF PET/CT. It may be used to identify bone metastases. Figure 2 illustrates the common clinical indications as 9 outlined by Society of Nuclear Medicine. Page 4 of 24

Fig. 2: Common clincical indications for the use of F-18 NaF PET/CT as outlined by the Society of Nuclear Medicine. Page 5 of 24

References: Segall G, Delbeke D, Stabin MG, et al. SNM guideline for sodium 18Ffluoride PET/CT bone scan 1.0. J Nucl Med. 2010; 51:1813-1820. Findings and procedure details Patient population From March - December 2013, 24 patients with known malignancies and equivocal conventional imaging studies were examined with F-18 NaF PET/CT. Of these patients, 11 patients had breast carcinoma and the remaining 13 patients had prostate carcinoma. Mean age was 63 years (range 48-88 years). Imaging protocol A patient questionnaire was completed prior to imaging with particular emphasis on skeletal injury and pathology. Patient height and weight was recorded. A dose of 180-220 MBq F-18 NaF was administered intravenously depending on patient weight. PET/CT was performed approximately 60 minutes post administration. In our department, patients are imaged using a GE Discovery VCT 64 Slice PET/CT system. The typical scan range was vertex to knees with patient supine with arms down. A low dose helical noncontrast CT was performed (pitch 1.375:1, kvp 120 kv, automodulated mas). PET was performed with 2 minutes per bed position. Interpretation Images were interpreted on the PET/CT GE Advantage workstation and compared to Tc-99m MDP BS, CT and MRI where available. Clinical cases: Case 1: A 61 year old female patient presented for staging CT for recurrent breast carcinoma. CT demonstrated diffuse sclerotic bone lesions in the vertebral bodies and pelvis (Figure 3). Tc-99m MDP BS on the same day was negative for bone metastases (Figure 4). The patient proceeded to F-18 NaF PET/CT which demonstrated widespread F-18 NaF avid bone metastases (Figure 5). Page 6 of 24

Fig. 3: Coronal and sagittal noncontrast CT demonstrating diffuse sclerotic lesions throughout the vertebral bodies and pelvis. Page 7 of 24

Fig. 4: Tc-99m MDP BS demonstrating physiological distribution of radiotracer. Page 8 of 24

Fig. 5: F-18 NaF PET/CT MIP image demonstrating diffusely increased radiotracer uptake throughout the axial and appendicular skeleton (a) and axial PET (b), axial noncontrast CT (c) and axial fused images (d) of the pelvis demonstrating diffuse sclerotic osseous lesions with increased radiotracer uptake. Case 2: A 47 year old female patient with known breast carcinoma presented with left anterior chest wall pain. Tc-99m MDP BS demonstrated increased radiotracer uptake in T12 vertebral body and in the skull base without corresponding abnormality on plain film (Figure 6). F-18 NaF PET/CT demonstrated increased radiotracer uptake in a lytic lesion in the skull base as well as mixed sclerotic and lytic lesions in T12 vertebral body and left hemisacrum (Figure 7). Page 9 of 24

Fig. 6: Tc-99m MDP BS demonstrating increased radiotracer uptake in T12 vertebral body and in the right skull base. Page 10 of 24

Fig. 7: F-18 NaF PET/CT MIP image demonstrating increased radiotracer uptake in the skull base, T12 vertebral body and left hemisacrum (a) and axial PET (b), axial noncontrast CT (c) and axial fused images (d) of T12 vertebral body demonstrating a F-18 NaF-avid mixed sclerotic and lytic lesion. Case 3: A 55 year-old male presented with prostate-specific antigen (PSA) 49 µg/l and Gleason 9 prostate carcinoma with nodal metastases. Tc-99m MDP BS was negative for bone metastases (Figure 8). Restaging CT following treatment demonstrated an increasing sclerotic lesion in the right femoral head (Figure 9). F-18 NaF PET/CT demonstrated multiple F-18 NaF-avid bone metastases (Figure 10). Page 11 of 24

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Fig. 8: Tc-99m MDP BS demonstrating physiological uptake of radiotracer. Fig. 9: Coronal noncontrast CT demonstrating a sclerotic lesion in the right femoral head. Page 13 of 24

Fig. 10: F-18 NaF PET/CT MIP image demonstrating multiple foci of increased radiotracer uptake (a) and axial PET (b), axial noncontrast CT (c) and axial fused images (d) demonstrating a F-18 NaF-avid sclerotic lesion in the right femoral head. Case 4: A 67 year-old male with Gleason 9 prostate carcinoma with known metastases to T9 vertebral body presents with rising PSA. Initial Tc-99m MDP BS demonstrated increased radiotracer uptake in T9 vertebral body (Figure 11). Restaging F-18 NaF PET/ CT demonstrated multifocal increased radiotracer uptake throughout the axial skeleton consistent with widespread osseous metastases (Figure 12). Page 14 of 24

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Fig. 11: Tc-99m MDP BS demonstrating increased radiotracer uptake in T9 vertebral body. Fig. 12: F-18 NaF PET/CT MIP image demonstrating multifocal increased radiotracer uptake (a) and axial PET (b), axial noncontrast CT (c) and axial fused images (d) of the pelvis demonstrating diffusely increased radiotracer uptake corresponding to multiple sclerotic osseous lesions. Case 5: Page 16 of 24

A 67 year old male patient presented with rising PSA on a background of previous Gleason 6 prostate carcinoma. Tc-99m MDP BS demonstrated a degenerative pattern of radiotracer uptake (Figure 13). The patient proceeded to F-18 NaF PET/CT which confirmed multifocal radiotracer uptake correlating with degenerative change (Figure 14). However there was an incidental 3 cm left iliac chain lymph node suspicious for metastatic disease (Figure 15). Fig. 13: Tc-99m MDP BS demonstrating a degenerative pattern of radiotracer uptake. Page 17 of 24

Fig. 14: F-18 NaF PET/CT MIP image demonstrating multifocal increased radiotracer uptake (a) and axial PET (b), axial noncontrast CT (c) and axial fused images (d) at the level of L1/L2 demonstrating increased radiotracer uptake corresponding to degenerative disease. Page 18 of 24

Fig. 15: Axial PET (a), axial noncontrast CT (b) and axial fused images (c) of the pelvis demonstrating a 3 cm left iliac chain lymph node. Case 6: A 64 year-old female with a history of bilateral breast carcinoma presents for staging Tc-99m MDP BS. This demonstrated indeterminate uptake in the body of the sternum (Figure 16). Subsequent CT demonstrated an ill-defined sclerotic lesion in the body of the sternum (Figure 17). Subsequently F-18 NaF PET/CT demonstrated very mild radiotracer uptake in the lesion favouring benign degenerative disease (Figure 18). Page 19 of 24

Fig. 16: Tc-99m MDP BS demonstrating abnormal radiotracer uptake in the sternum. Page 20 of 24

Fig. 17: Sagittal noncontrast CT demonstrating ill-defined sclerotic lesion in the body of the sternum. Page 21 of 24

Fig. 18: F-18 NaF PET/CT MIP image (a) and coronal and axial PET (b-c), axial noncontrast CT (d) and axial fused images (e) of the sternum demonstrating an illdefined sclerotic lesion in the body of the sternum with mild radiotracer uptake. Conclusion The favourable pharmacokinetic characteristics of F-18 NaF and high quality skeletal imaging provided with PET/CT make F-18 NaF PET/CT an accurate imaging modality in the detection of bone metastases. In our institution, F-18 NaF PET/CT has proved clinically useful in the detection and exclusion of bone metastases when other imaging modalities were normal or equivocal. Patients have also been upstaged according to incidental extraskeletal findings on CT. This technique can help identify bone metastases and their associated complications early, enabling accurate staging of disease and appropriate treatment decisions. Page 22 of 24

Personal information J. Murphy, Department of Radiology, Cork University Hospital, Wilton, Cork, Ireland. M. O'Keeffe, Department of Radiology, Cork University Hospital, Wilton, Cork, Ireland. P. Nicholson, Department of Radiology, Cork University Hospital, Wilton, Cork, Ireland. K. James, Department of Radiology, Cork University Hospital, Wilton, Cork, Ireland. K. O'Regan, Department of Radiology, Cork University Hospital, Wilton, Cork, Ireland. References 1. 2. 3. 4. 5. 6. 7. 8. 9. Even-Sapir E, Metser U, Mishani E, et al. The detection of bone metastases in patients with high-risk prostate cancer: 99mTc-MDP planar bone scintigraphy, single- and multi-field-of-view SPECT, 18Ffluoride PET, and 18F-fluoride PET/CT. J Nucl Med. 2006;47:287-297. Even-Sapir E, Metser U, Flusser G, et al. Assessment of malignant skeletal disease: initial experience with 18F-fluoride PET/CT and comparison between 18F-fluoride PET and 18F-fluoride PET/CT.. 2004;45:272-278.J Nucl Med Blau M, Nagler W, Bender MA. Fluorine-18: a new isotope for bone scanning. J Nucl Med 1962;3:332-4. Muindi J, Coombes RC, Golding S, et al. The role of computed tomography in the detection of bone metastases in breast cancer patients. Br J Radiol. 1983;56:233-236. Schirrmeister H, Glatting G, Hetzel J, et al. Prospective evaluation of clinical value of planar bone scan, SPECT and 18F-labeled NaF PET in newly diagnosed lung cancer. J Nucl Med. 2001;42:1800-1804. Huyge V, Garcia C, Vanderstappen A, Alexiou J, Gil T, Flamen P.Progressive osteoblastic bone metastases in breast cancer negative on FDG-PET. Clin Nucl Med. 2009;34(7):417-20. Nakai T, Okuyama C, Kubota T, Yamada K, Ushijima Y, Taniike K, et al. Pitfalls of FDG-PET for the diagnosis of osteoblastic bone metastases in patients with breast cancer. Eur J Nucl Med Mol Imaging. 2005;32(11):1253-8. Cook GJ, Houston S, Rubens R, Maisey MN, Fogelman I. Detection of bone metastases in breast cancer by 18FDG PET: differing metabolic activity in osteoblastic and osteolytic lesions. J Clin Oncol. 1998;16(10):3375-9. Segall G, Delbeke D, Stabin MG, et al. SNM guideline for sodium 18Ffluoride PET/CT bone scan 1.0. J Nucl Med. 2010; 51:1813-1820. Page 23 of 24

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