81 SPECT/CT in the post-operative painful knee difficult clinical problem remains dependent on a combination of clinical, laboratory, microbiology, and imaging tests. In suspected infection, BS SPECT/CT will display increased BTO in all three phases, but this is nonspecific in discriminating between aseptic loosening with sterile inflammation from infection. Dual-time labeled white blood cell (WBC) and bone marrow (BM) SPECT/CT is more specific for infection and shows enhanced uptake around the infected component, which increases between the first and second imaging timepoints Already in 2001, Van Acker described the superior specificity of combined WBC SPECT with BS or bone marrow imaging over FDG-PET in 21 patients with suspected infectious TKA [58]. Most other studies describe the role of SPECT/CT (and/or PET/CT) in infected hip as well as knee PJI and may not be limited to patients with prosthesis [45, 51, 59]. In suspected TKA infection it is advisable to start with an X-ray and 3-phase BS including SPECT/CT to exclude other pathology than infected TKA components. A completely negative 3-phase bone-scintigraphy rules out infection. Subsequently, either dual-timeWBC/bonemarrow imaging (at 3 and 24 hours p.i.) or antigranulocyte antibody/bone marrow (AGAB) scintigraphy at 3 and 6-8 hours p.i. is warranted [37, 45, 52, 60]. In a study by Filippi, et al. in 2006 with 28 consecutive patients, 99mTcHMPAO-leukocytes SPECT/CT added a significant clinical contribution in 35.7% of the patients. SPECT/CT discriminated soft-tissue from bone involvement in patients with orthopedic implants, and identified synovial infection without prosthesis involvement in patients with a knee implant [51]. The images yielded by any tracer or modality should therefore always be placed in the context of the other findings. Suggested flowcharts in suspected PJI are therefore either complex or they oversimplify the difficult trajectory of reliably diagnosing PJI. Today, there are no widely accepted multidisciplinary guidelines, but if these emerge they will probably encompass the clinical clues for infection (redness, pain, fever, swelling, and impaired range of motion), microbiological cultures, laboratory test (white blood cell count, C-reactive protein), bone or soft tissue biopsy, and conventional radiography, all preceding radionuclide imaging [37]. Different types of radionuclide imaging may be used, depending whether an acute, delayed or late infection is suspected. Combined in vitro labelledWBC/bone marrow scintigraphy is currently the imaging modality of choice for diagnosing PJI, reaching an accuracy of about 90% [45, 47].A study by Graute, et al. in 31 patients with hip and knee prosthesis and using 99mTc-labelled antigranulocyte antibodies (AGAB) SPECT/CT showed a sensitivity, specificity, positive and negative predictive values of 89%, 73%, 57% and 94% for the diagnosis of infection [52]. A summary of these indications is given in Table 4. 3