Critical Reviews in Oncology/Hematology 101 (2016) 169–183 Contents lists available at ScienceDirect Critical Reviews in Oncology/Hematology jo ur nal homep age: www.elsevier.com/locate/critrevonc Myeloma bone and extra-medullary disease: Role of PET/CT and other whole-body imaging techniques Giuseppe Rubini a , Artor Niccoli-Asabella a,∗ , Cristina Ferrari a , Vito Racanelli b , Nicola Maggialetti c , Francesco Dammacco b a Nuclear Medicine Unit, University of Bari Medical School, Bari, Italy b Department of Internal Medicine and Clinical Oncology, Guido Baccelli Unit, University of Bari Medical School, Bari, Italy c Department of Medicine and Health Science, Radiodiagnostic Section, University of Molise, Campobasso, Italy Contents 1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 170 2. Pathogenesis of MM-related bone disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 170 3. Imaging features . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 171 3.1. Technical features . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 171 3.2. Clinical features . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 171 3.2.1. Imaging in the diagnosis and staging . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 171 3.2.2. Imaging of response to treatment and disease progression . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 176 4. Usefulness of imaging: what and when? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 178 5. Imaging of the future . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 180 6. Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 181 Conflict of interest . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 181 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 181 Biographies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 183 a r t i c l e i n f o Article history: Received 16 December 2014 Received in revised form 8 February 2016 Accepted 3 March 2016 Keywords: Bone disease Diffusion weighted whole body imaging with background body signal suppression (DWIBS) Multiple myeloma Positron emission tomography/computed tomography (PET/CT) Positron emission tomography/magnetic resonance (PET/MR) Whole body magnetic resonance (WB-MR) a b s t r a c t Multiple myeloma (MM) is the second most common hematological malignancy. Although it can affect different organs, the bone compartment stands out both in terms of prevalence and clinical impact. Despite the striking advances in MM therapy, bone disease can remarkably affect the patient’s quality of life. The occurrence and extension of bone marrow and extra-medullary involvement should be carefully assessed to confirm the diagnosis, to locate and whenever possible prevent dreadful complications such as pathological fractures and spinal cord compression, and to establish suitable therapeutic measures. Many imaging techniques have been proposed for the detection of MM skeletal involvement. With the development of more sophisticated imaging tools, it is time to use the right technique at the right time. Based on the review of the literature and our own experience, this article discusses advantages and dis- advantages of the different imaging methods in the work-up of MM patients, with particular emphasis on the role that PET/CT can play. It is emphasized that whole body low-dose computed tomography should be the preferred imaging technique at baseline. However, bone marrow infiltration and extra- medullary manifestations are better detected by whole body magnetic resonance imaging. Positron emission tomography/computed tomography, on the other hand, combines the benefits of the two Abbreviations: [11C]CHO, [11C]Choline; [11C]MET, [11C]Methionine; [18F]FDG-PET/CT, 2-deoxy-2-[18F]fluoro-d-glucose-positron emission tomogra- phy/computed tomography; [18F]FLT, 3 ′ -[18F]fluoro-3 ′ -deoxy-l-thymidine; [18F]NaF, [18F]sodium-fluoride; [99mTc]MDP, [99mtechnetium]methylene-diphosphonate; [99mTc]sestaMIBI, 2-methoxy-isobutyl-isonitrile[99mTc]technetium; ASCT, autologous hematopoietic stem cell transplantation; BS, bone scintigraphy; CRAB, hyper- calcemia, renal involvement, anemia, lytic bone lesions; FoV, field of view; GLUT, glucose transporter; IMWG, International Myeloma Working Group; MGUS, monoclonal gammopathy of undetermined significance; MM, multiple myeloma; MRD, minimal residual disease; MTV, metabolic tumor volume; OS, overall survival; PFS, progression free survival; PPV, positive predictive value; SBP, solitary bone plasmacytoma; SMM, smoldering multiple myeloma; STIR, short time inversion recovery; SUVmax, maximum standardized uptake value; T1w, T1-weighted; T2w, T2-weighted; TLG, total lesion glycolysis; TTP, time to progression; WB-LDCT, whole body low dose computed tomography; WB-MDCT, whole body multidetector computed tomography; WB-MR, whole body magnetic resonance; WB-MR/DWIBS, WB-MR/diffusion-weighted imaging with background body signal suppression; WB-XR, whole body skeletal X-ray. ∗ Corresponding authors at: Piazza G. Cesare, 11, Bari 70124, Italy. E-mail address: artor.niccoliasabella@uniba.it (A. Niccoli-Asabella). http://dx.doi.org/10.1016/j.critrevonc.2016.03.006 1040-8428/© 2016 Elsevier Ireland Ltd. All rights reserved.