Fig. 1. Normal bone scintigraphy.

98 12 Chapters on Nuclear Medicine

The objective of this chapter is to make a simple but detailed review of the main nuclear medicine clinical applications in the appraisal and management of musculoskeletal problems.

Bone scan is a diagnostic technique used to assess the presence of anomalies in the distribution pattern of bone formation. It has high sensitivity, but specificity is frequently variable or limited. Three-phase bone scintigraphy is currently the most used technique because it allows evaluating the degree of hyperemia (flow phase), increased of articular permeability (blood pool phase) and the presence of alterations in bone remodeling (bone tissue phase). Traditional technique is based on the biological properties of bisphosphonates marked with 99mTc, usually MDP, when they are integrated into the bone metabolism after intravenous administration. Typically, 30% of the injected dose of Tc-99m-MDP remains in the skeleton, and most of bone uptake occurs in the first hour. The remainder is eliminated from the tissues and blood by the kidneys and imaging is obtained 3 – 4 hours later. In general, uptake of the tracer depends on local blood flow, osteoblastic activity and extraction efficiency. Normal scintigraphy imaging depends on technical equipment and employees, but it is also significantly influenced by other factors such as age and constitution of the patient, intake of drugs, degree of hydration, renal function and/or the presence of impaired circulation. Therefore a whole body study is recommended, with anterior and posterior screenings that allows assessing the symmetry or asymmetry in the distribution of the drug. However, a located study may be sufficient in some cases, since provides greater image quality and requires less time and is less expensive. In other patients, especially when a spine study is necessary or avascular osteonecrosis located in the hip or knee is suspected, it will require a SPECT, that is more sensitive for detecting

abnormalities and provides, combined with tomography, three-dimensional images.

radiotracers are eliminated by the kidneys (Murray, 1998; Schneider, 2006).

It is necessary to have knowledge of normal variants and patterns of abnormality to minimize misinterpretation. Whole body bone scan shows normal variations in the uptake of the radiotracer, as this is higher in areas with high bone remodeling. The age of the patient has a fundamental role in the appearance of the scan, especially during the growth period and in the elderly. In children, as they have a growing skeleton, there is a diffuse bone uptake and a striking uptake at the growth plates of bones, especially in metaphysealepiphyseal areas of long bones and cranial sutures. This decreases over the years until complete fusion of the epiphyses takes place. On the other hand, bone scan images are often of poor quality in old people. Aging may be reflected in scintigraphic images by a diffuse reduction of bone uptake of the radioisotope, although diffuse uptake at the dome or symmetrical uptake in the peripheral joints (secondary to osteoarthritis) may be present. Associated degenerative processes may lead to increased uptake in the involved joints. Obese people also get lower quality images. In addition, insufficient hydration and/or renal failure hamper the radiopharmaceutical removal of soft tissues and modify the end result. The sternum and the sacroiliacs joints are normal uptake areas in scintigraphic studies (**Fig. 1**). Other areas that may appear as normal increased uptake (**table 1**) are forewings of the iliac bone, coracoid process, tip of the scapula and, sometimes, costochondral junction, lower portion of the cervical spine, kneecaps and some muscle attachments. Thoracic kyphosis and lumbar lordosis may cause the parts of the column that are farther away, appear as less warm. In patients with scoliosis, concave side usually appears hotter than the convex. There is also a physiological uptake located at renal pelvis and the bladder, since

**2. Normal bone scintigraphy** 


Table 1. Normal Variants of uptake on 99mTc-MDP Bone Scan.

Many causes may lead to false pathologic imaging or pitfalls (Naddaf et al., 2004). Bladder diverticula or bladder image over pubic bones, urine leakage or urinary retention and patient rotation are some common examples. Artifacts on bone scintigraphy can be technical or patient-related (**Table 2**). The technical artifacts include equipment, radiopharmaceutical, and image processing-related problems. Equipment-related artifacts may be due to inadequate quality-control procedures and calibration. Faulty radiopharmaceutical preparation alters biodistribution and can compromise the diagnostic quality of the images. Increased tracer uptake in the stomach, thyroid, and salivary glands can be seen if there is free pertechnetate, in the radiopharmaceutical. A number of factors, for example, presence of reduced aluminum ions, if the radiopharmaceutical is left unused for a long time, inappropriately high pH and addition of dextrose solutions, may affect uptake of radioactivity in bone.

Finally, the most common artifact on the bone scan is due to extravasation at the site of injection, that may occasionally cause confusion with a bone abnormality, and it is therefore important to document the site of injection in all patients. Further, ipsilateral lymph node(s) may be seen due to extravasation of radiotracer and can on occasion cause confusion,

Nuclear Medicine in Musculoskeletal Disorders: Clinical Approach 101

1988). The intensity of uptake on scintigraphy is correlated to some clinical and laboratory indexes of disease activity (De Leonardis et al., 2008; as cited in Park et al., 1977) and the monitoring during treatment can evaluate the effectiveness of it (De Leonardis et al., 2008; as cited in Palmer et al., 1993; Elzinga et al., 2010). It is also a useful technique when an additional pathology (eg, osteonecrosis, stress fractures or metastatis) is suspected. Furthermore, in patients with nonspecific polyarthralgia, normal bone scan excludes the presence of active arthritis (Colamussi et al., 2004; as cited in Shearman et al., 1982). It is a sensitive tool but not highly specific, and may be altered in other diseases such as osteoarthritis. Nevertheless, planar bone scintigraphy is clearly less sensitive than SPECT in the evaluation of early stages of this disease or mild abnormalities. Multipinhole SPECT of the hands has been used to identify patients with minimal changes in bone metabolism (Gotthardt et al., 2010). This technique proven to equal MRI in sensitivity and also detected increased bone metabolism in two patients in whom MRI had negative results, demonstrating that multipinhole SPECT may be even more sensitive than MRI in some cases (Gotthardt et al., 2010; as cited in Ostendorf et al., 2010). PET may also be used for imaging of synovial inflammation. The most commonly used radiotracer in clinical PET scanning is fluorodeoxyglucose (18F-FDG), and since inflammation is a glucose-avid oxidative process, 18F-FDG-PET allows a quantitative measurement of the uptake of tracer concentration with a positive correlation with the degree of joint inflammation in patients with RA. Recently, it has been demonstrated its correlation with parameters of disease activity (swelling, tenderness, serum markers) and findings from gold standard techniques such as US and MRI. This quantitative assessment could be useful for evaluating the therapeutic effectiveness. Besides 18F-FDG, tracers such as 11C-choline may be used for measurement of cell proliferation and evaluation of synovitis with high accuracy (Gotthardt et al., 2010; as cited in Roivainen, 2003). Other techniques, including the imaging of sinovitis with 99mTc-nanocolloids, have shown high sensitivity and specificity in this field. Thus, nuclear medicine techniques, especially PET and multipinhole SPECT of small joints, may play a role in identifying RA at an early stage, but the usefulness of these techniques compared with MRI and US needs to be proven in RA imaging. Currently, US and MRI are the techniques of choice for serial assessments of patients with RA due to practical reasons and the required exposure of the patient to radiation in the nuclear medicine studies. Large systematic prospective studies on the efficient use of imaging modalities to assess the efficacy of treatment in early RA are lacking. Nevertheless, new imaging modalities are assuming an important role in the investigation and management of RA. Tagging important cellular and protein mediator may allow us improving the knowledge of RA pathophysiology. In recent years, the use of labelled immunoglobulins (Igs) that head for areas of inflammation and where they stay accumulated (aspecific polyclonal IgG-type

antibodies labelled in most cases with Tc-99m), has been developed (**Table 3**).

Infliximab (Remicade) Chimeric IgG1 Adalimumab (Humira) Fully human IgG1 Rituximab (Rituxan/Mabthera) Chimeric IgG1 MAX.16H5 Murine IgG1 1.2B6 Murine IgG1 OKT-3 (Muromonab) Murine IgG2

mAbs Type Class Isotope Target

Table 3. Molecular imaging of RA by radiolabelled monoclonal antibody (mAbs).

99mTc 99mTc 99mTc 99mTc 111In 99mTc TNF-α TNF-α CD20 CD4 E-selectin CD3


Table 2. Common Artifacts in Bone Scintigraphy.

particularly if overlying the scapula or a rib (Gnanasegaran et al., 2009). Photon-deficient areas commonly seen on the bone scan are due to metallic objects. Patients should be asked to remove metallic objects wherever possible before performing the scan. Urinary contamination is a common problem, which may simulate focal lesions, especially if close to or overlying the bone. It is useful to remove the clothing or to wash the skin and reimage the patient around the region of interest to avoid any confusion. The patient should void before the study and rarely delayed imaging or bladder catheterization may be required. Further, radioactive urine in the bladder is a frequent cause of artifact in patients evaluated with SPECT for pelvic metastases (prostate cancer) or low-back pain. Increased radioactive urine in the bladder can cause streak artifacts on the reconstructed images and overlap bony structures. Further, intense tracer retention in the bladder is reported to cause pixel overload, resulting in a relatively cold area close to the region of interest of the femoral heads, which hinders its interpretation.
