Editorial Comment: Extra-Skeletal Uptake of Bone Agents

The nuclear medicine literature is rich with reports of both normal and abnormal accumulation of bone imaging agents (99m Tc-HDP, MDP or PYP) in extra-skeletal structures. The cases published in this issue of the Journal of Nuclear Medicine Technology are excellent examples of this phenomenon. Extraskeletal uptake is usually an incidental finding on the bone scan, although the bone scan occasionally can be done for the specific diagnostic intent of identifying extra-skeletal uptake. It is important for the nuclear medicine professional to be aware of the more common conditions that can present with extraskeletal uptake of the 99mTc bone agents. For a comprehensive listing of conditions associated with extra-skeletal uptake, the reader is referred to Dr. Datz’s excellent textbook (Datz FL. Gamuts in Nuclear Medicine, 2nd ed. Norwalk, CT: Appleton and Lange; 1987:97–132). Technetium-99m bone agents, pyrophosphate (PYP) and the newer generation diphosphonates (HDP, MDP) are small molecules that diffuse freely in the interstitial fluid, being available for uptake by most tissues in the body. Intravenously injected tracer first distributes in the interstitial fluid then localizes in bone, while the lymphatic system and blood stream gradually clear excess tracer from the interstitial space, with excretion by glomerular filtration. Clearance of the tracer by the kidneys is more efficient with MDP and HDP than with PYP. For this reason, when a bone scan is done for the express purpose of visualizing extra-skeletal structures, PYP often is used because it is available for uptake by soft tissues for a prolonged period of time. Sites of extra-skeletal involvement can be seen in normal circumstances. Mild generalized soft-tissue uptake, symmetric kidney uptake, and bladder uptake are normal findings. An absence of soft-tissue and kidney uptake, hence a ‘‘superscan’’ or ‘‘beautiful bone scan,’’ may indicate diffuse underlying skeletal pathology, such as metabolic bone disease or diffuse metastatic disease. However, this finding can occur in normal individuals when the time from injection to imaging is delayed longer than 4–5 h. Abnormal extra-skeletal uptake may be focal, within a specific organ or structure, or diffuse. Diffuse uptake may occur throughout the entire body, or within a specific extremity or region. Diffusely increased uptake throughout the body can indicate an increase in the extra-cellular volume of distribution of the tracer, such as with diffuse edema or anasarca. This finding also can indicate a decrease in clearance of the tracer from the kidneys, such as with renal failure or dehydration, or when a patient is imaged too soon after injection. Delayed (mineral phase) images should not occur earlier than 2 h postinjection. Additional delays may be required in patients who are poorly hydrated or who have renal failure. Intentional early imaging (tissue or blood-pool phase imaging) may be performed to identify sites or hyperemia. This strategy also has been used to enhance identification of soft-tissue tumors or areas of inflammation. Diffuse uptake of the tracer in a specific extremity or region usually indicates vascular obstruction, either venous or lymphatic. In these cases, there is often accentuation of the skin. In contrast, chronic venous insufficiency of the lower extremities usually presents as mild diffuse uptake, poor definition of the underlying bones, but lack of skin accentuation. Accentuation of the skin of the breast can be seen with obstruction of the dermal lymphatics by underlying breast cancer, a finding of similar significance to skin thickening on mammography. Skin uptake of bone agents also can be seen with inflammatory, desquamative or exudative dermatologic disorders. Focal uptake in extra-skeletal sites has a broad differential, depending on the organ or structure involved. Any heavily calcified structure in the body can take up the bone tracer. Larger structures will be more visible than small structures. However, intense bone tracer uptake can be seen in a variety of conditions in which no visible calcification is evident by plain film or CT. Radiopharmaceutical problems can cause extra-skeletal uptake of bone agents. Free 99mTc-pertechnetate characteristically results in uptake in the stomach, bowel, salivary glands, thyroid and, occasionally, choroid plexus. It often will demonstrate a ‘‘high background’’ of blood-pool and diffuse soft-tissue activity as well. The formation of colloid particles of 99mTc, which can result from crumbling of the 99Mo alumina column (a form of ‘‘aluminum breakthrough’’), can result in diffuse liver and spleen uptake when the size of the particles is less than 1 μM, or lung uptake when the particles are larger. Of course, the recent For correspondence or reprints contact: Kathryn A. Morton, MD, Chief, Imaging Service (P2 Imag), VA Medical Center, P.O. Box 1034, Portland, OR 97207.