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Art. 1.1475/Ringraziamenti European Review for Medical and Pharmacological Sciences 2012; 16(Suppl 2): 20-25 The role of nuclear medicine in the diagnosis of spondylodiscitis G. TREGLIA, C. FOCACCI, C. CALDARELLA, M.V. MATTOLI, M. SALSANO, S. TARALLI, A. GIORDANO Institute of Nuclear Medicine, School of Medicine, Catholic University of the Sacred Heart, Rome (Italy) Abstract. – Background: The diagnosis clusive, particularly in the early stages1,2. Nuclear of spondylodiscitis can be difficult, because the medicine procedures, which identify pathophysi- patients history, subjective symptoms and phys- ological reactions preceding morphological ical findings are often inconclusive, particularly changes, can play a useful role in the diagnosis in the early stages. Aim: To perform an overview on the role of of SP; several studies have investigated about the nuclear medicine procedures with single photon utility of nuclear medicine techniques with single emission tomography (SPET) and positron emis- photon emission tomography (SPET) and sion tomography (PET) tracers in the diagnosis positron emission tomography (PET) tracers in of spondylodiscitis. the early diagnosis, staging and post-treatment Materials and Methods: A literature review evaluation in patients with SP3. about bone scintigraphy, Gallium-67-citrate scintigraphy, labeled leukocytes scintigraphy and PET was performed. Main findings of the lit- erature were reported. Results: Bone scintigraphy is a sensitive and Role of nuclear medicine widely available nuclear medicine technique, but techniques with SPET tracers in it is characterized by low specificity. Gallium-67- patients with spondylodiscitis citrate scintigraphy is often used as a comple- ment to bone scintigraphy to enhance the speci- ficity of the study and to detect extra-osseous Conventional nuclear medicine techniques sites of infection. Labeled leukocytes scintigra- such as bone scintigraphy with Technetium-99m- phy is not a useful method in the diagnosis of diphosphonates, scintigraphy with autologous ra- spondylodiscitis. Fluorine-18-fluorodeoxyglucose diolabeled leukocytes and scintigraphy with Gal- positron emission tomography is a sensitive lium-67-citrate are to date performed in the diag- method and could potentially be useful in the di- nostic management of patients with bone infec- agnosis of spondylodiscitis and in the evaluation of treatment response. Nevertheless, scientific lit- tions, even though the wider availability of mag- erature about this topic is still limited. netic resonance (MRI) has considerably nar- Conclusions: Overall, nuclear medicine proce- rowed their application fields. dures play a useful role in the diagnosis of spondylodiscitis identifying functional abnormali- Bone scintigraphy with Technetium-99m- ties which precede morphological changes. There- diphosphonates fore, nuclear medicine procedures may comple- Bone scan with Technetium-99m-diphospho- ment or integrate morphological imaging findings in patients with suspected spondylodiscitis. nates allows to detect sites of bone remodeling, which can be determined by either an infectious Key words: condition or any other pathological process of the spine characterized by accelerated bone turnover Nuclear medicine, Spondylodiscitis, Scintigraphy, (rheumatic and degenerative osteo-articular dis- Positron Emission Tomography. eases, osteoporosis fractures, pseudo-arthrosis, neoplastic involvement)4-6. Bone scintigraphy for the diagnosis of bone infection is usually per- Introduction formed with a three-phase modality: a dynamic “angiographic sequence” for the study of hyper- The diagnosis of spondylodiscitis (SP) can be emia; a “blood-pool image” to detect inflamma- difficult, because the patients history, subjective tory involvement of soft tissues; a “later (or symptoms and physical findings are often incon- bone) image” (after at least 2-3 hours) to investi- 20 Corresponding Author: Giorgio Treglia, MD; e-mail: [email protected] The role of nuclear medicine in the diagnosis of spondylodiscitis gate bone turnover4-6. In SP, the radiopharmaceu- culature in the affected bone is needed to allow tical uptake is centered about the disk space and an adequate accumulation of the radiopharma- adjacent vertebral bodies and has a vertical orien- ceutical, false negative results may be the conse- tation. Early SP typically shows increased tracer quence of inadequate blood supply (vasospasm, uptake on bone scintigraphy despite normal find- thrombosis of vessels, oedema), lytic lesions ings on radiographs (Figure 1)5. with loss of osseous tissue or subperiosteal ab- Performing an hybrid tomographic single pho- scesses9-13. Nevertheless, abnormalities seen on ton emission tomography/computed tomography bone scintigraphy do not reflect infection specifi- (SPECT/CT) acquisition provides a higher speci- cally, hence specificity is low, especially in the ficity than planar scans; in fact, the improved setting of previous vertebral surgery (e.g. pros- anatomical localization of sites of abnormal ra- thetic implants) or injuries9-13. diopharmaceutical uptake in different vertebral components is useful to distinguish between dif- ferent spinal diseases which follow certain pre- Scintigraphy with autologous dictable patterns7,8. radiolabeled leukocytes Overall, bone scintigraphy with Technetium- Leukocytes, and particularly neutrophils, sig- 99m-diphosphonates is well known for its high nificantly accumulate in the site of infection to sensitivity, ranging from 80 to 95%, much take part in the inflammatory response against greater than conventional x-ray in the early diag- the microbial agent. Therefore, scintigraphy with nosis of SP: in fact, alterations in local blood autologous radiolabeled leukocytes is a potential- supply and in bone turnover detected by bone ly useful diagnostic tool in patients with spine in- scan occur far before anatomical changes9-13. Fur- fection. Leukocytes labeling is obtained with thermore, if antibiotic therapy is initiated in early Technetium-99m-hexamethylpropylene amine stage, radiological abnormalities could not be ap- oxime (99mTc-HMPAO) or Indium-111-oxine, parent9-13. Thanks to its high sensitivity, a normal even if the latter method has become obsolete for bone scintigraphy provides very reliable evi- most indications because of poor image resolu- dence for the absence of bone inflammation; on tion14. However, disregarding the biological risk the contrary, an increased uptake in all phases is related to the manipulation of infected blood, the suggestive. Besides, the scanning of the entire physiological uptake of leukocytes by the body allows the detection of eventual clinically hematopoietically active bone marrow (which silent infectious focuses, whether in the spine can be found in the axial bone segments such as and in other bone segments. Since an intact vas- the skull, clavicles, sternum, scapulae, ribs, ver- tebrae and pelvis) is the major drawback which reduces the sensitivity of this method in the diag- nosis of SP15. Palestro et al16 reported a low sen- sitivity (39%) of scintigraphy with labeled leuko- cytes in patients with SP when increased verte- bral labeled leukocytes uptake was considered, while specificity was very high (98%). Pho- topenic lesions at scintigraphy with labeled leukocytes are shown in about 50% of patients affected by SP, probably due to encapsulation of the infected site and therefore reduced migration of leukocytes16,17; nevertheless, this pattern is nonspecific for infection. Scintigraphy with Gallium-67-citrate Infectious foci usually show high concentra- tions of Gallium-67-citrate. Several mechanisms have been proposed: binding to transferrin result- Figure 1. Bone scintigraphy with Technetium-99m-diphos- phonates planar image (posterior view) in a 44 year-old fe- ing in deposit to the sites of increased vascular male patient with spondylodiscitis showing increased tracer membrane permeability; binding to lactoferrin, a uptake between D12 and L1. globular glycoprotein with antimicrobial activity, 21 G. Treglia, C. Focacci, C. Caldarella, M.V. Mattoli, M. Salsano, S. Taralli, A. Giordano produced by innate immunitary system and abun- dant in the site of infection; direct uptake by cer- tain bacteria through siderophores18,19. The major drawback of Gallium-67-citrate scintigraphy is that only a small amount of the injected dose is retained by the bone, whereas a great amount is retained by the liver, bone marrow and soft tis- sues at 48 h and the 25% is physiologically ex- creted through the urinary system and the colon within the first 24 h20. Furthermore, poor image quality, high bowel uptake in the early images requiring delayed images (up to 48-72 h) to re- duce intestinal activity, nonspecific tumor and nodal uptake and an unfavourable physical half- life reduce the diagnostic yield of this method20,21. Nevertheless, chronic infections of the spine are correctly identified by Gallium-67- citrate scintigraphy22-24 (Figure 2). Moreover, Gallium-67-citrate scintigraphy should be per- formed regardless of the findings of a contempo- raneous bone scan: in fact, it improves the sensi- tivity and the specificity of bone scan and de- tects soft tissue involvement especially if per- formed with SPECT/CT modality22-24. Love et al24 found that Gallium-67-citrate SPECT is more accurate than bone scintigraphy with Tech- netium-99m-diphosphonates (92% vs 71%), as sensitive as MRI (91%) and slightly more spe- cific than MRI (92% vs 77%). These Authors suggested that Gallium-67-citrate SPECT should
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