Applied Radiology

Bone imaging using Technetium-99m-methylene diphosphonate (Tc-99m-MDP) is one of the most frequently used studies in nuclear imaging due to its high sensitivity and rapid ability to detect bone abnormalities in the entire skeleton with little radiation given to the patient.

There are several entities which cause non-osseous accumulation of the radionuclide. The mechanisms responsible for soft-tissue activity include increased blood perfusion, necrosis with or without calcification, hypercalcemia, presence of collagen, faulty preparation of the radionuclide, or decreased excretion.1,2 This presentation reviews the common causes of soft-tissue uptake of Tc-99m-MDP.

Neoplastic disease

The liver is a common site for metastatic deposits, and focal areas of increased activity can be seen in necrotic lesions with or without calcifications. The mechanism for uptake in necrotic tumors is poorly understood; however, binding to macromolecules has been postulated, although the degree of uptake and consistency with which it is seen is not sufficient for routine use.3

In one example, a patient with a history of colon carcinoma who had a prior normal bone scan in April 1993 developed calcified metastatic lesions which were imaged in the liver on computed tomography (CT) in December 1993. A bone scan at that time also demonstrated abnormal radionuclide activity in the liver (figure 1).

Whole body images in another patient, status post-left mastectomy with necrotic liver metastases, reveal abnormal accumulation in the liver (figure 2); no calcification was present at the time of CT.1

Ultrasound typically is the first imaging modality used for patients complaining of right upper quadrant pain. In one such patient, multiple abnormal hyperechoic nodules of the liver were identified which proved to be metastatic deposits from lung carcinoma (figure 3A). A radionuclide bone scan was later obtained to evaluate occult bone pain; this revealed abnormal soft-tissue accumulation in the hepatic lesions (figure 3B).

Metastatic lesions which can produce a chondroid matrix or those that ossify also may be detected with bone scanning. We have seen an example of this in a patient who underwent left leg amputation for osteosarcoma who presented with two abnormal thoracic foci on whole body bone imaging (figure 4A); this correlated with metastatic osteosarcoma in the lung (figure 4B).

Primary soft-tissue or bone neoplasms can result in abnormal soft-tissue activity. The patient in figure 5 demonstrated abnormal uptake in the left breast which was caused by breast carcinoma. Abnormal radionuclide uptake within the breasts also may result from breast prosthesis or can be drug-induced.4,5

A patient with a primary Ewing's sarcoma of the left femur demonstrates abnormal enlargement of the hip and thigh with abnormal uptake, as seen in figure 6. A metastatic lesion in the skull is noted incidentally. Uptake in the soft tissues also can be secondary to benign soft-tissue tumors.6 The mechanism for such uptake is thought to be due to hyperemia and increased blood flow to these lesions.

Increased blood flow and vascular permeability with or without calcification are felt to be responsible for Tc-99m-MDP accumulation in ascitic, pericardial, and pleural fluid. The etiologies include uremic renal disease, infection, and tumor. Figure 7 shows a patient with abnormal uptake in the right chest which was a result of malignant pleural effusion.

The patient in figure 8A underwent mastectomy for breast carcinoma and presented with a metastatic focus in the left sacral wing which resulted from the malignancy. This patient received chemotherapy and underwent another bone scan, seen in figure 8B, which showed increased activity both in the metastases and in the kidneys. This flare response is a result of healing bone lesions, which show increased activity on bone scans secondary to the osteoblastic response. With successful treatment of metastatic disease through the use of chemotherapeutic drugs or radiation, the osteoblasts lay down new bone as the invasive neoplasm is suppressed. Although the flare response is rare, we try to image patients at least 4 months after chemotherapy or radiation as a precaution.

Increased renal uptake may be observed secondary to the effect of chemotherapeutic drugs, including bleomycin, cyclophosphamide, doxorubicin, mitomycin C and 6-mercaptopurine, as well as post radiation therapy due to the resultant small-vessel damage.7 Other causes of abnormal uptake in the kidneys may be secondary to metastatic calcification, pyelonephritis, acute tubular necrosis, iron overload, multiple myeloma, and obstruction of the ureters or renal veins.7,8

The mechanism of uptake for benign tumors and tumor-like conditions are likely similar to that of malignant neoplasms. As an example, two patients who presented complaining of hip pain are shown with abnormal accumulation of the radionuclide which proved to be synovial chondromatosis (figures 9A and 9B) and tumoral calcinosis (figures 9C and 9D), respectively.

Trauma

Abnormal soft-tissue uptake of Tc-99m-MDP has been found to occur after muscle trauma. The abnormal accumulation in this scenario has been postulated to result from increased tissue calcification of the damaged muscles, denatured proteins, changes in tissue hormone receptors, and immature collagen.9

Commonly, abnormal uptake is seen in patients, fit or unfit, who change their amount of exercise abruptly.10 The patient seen in figure 10 is a fit, active duty marine who was injured while engaging in a day-long pull-up contest. Marked abnormal accumulation in the soft tissues of the shoulders is demonstrated, most likely in the latissimus dorsi muscles. These patients usually are treated conservatively with analgesics and rest.

Acute traumatic muscle injury can result in hematoma formation which, if not completely resolved, may develop chondrogenesis and the formation of lamellar bone, an entity known as myositis ossificans;11 approximately 50% of patients with myositis ossificans present without a history of previous trauma.12 Myositis ossificans typically has a dense outer shell, with a paucity of internal calcification which helps the clinician differentiate this entity from a rare aggressive soft-tissue osteosarcoma that has a prominent central matrix.

A 29-year-old male patient with AIDS was admitted with a fever of unknown origin and an open wound in the sacral region. A bone scan was obtained which demonstrated no abnormal activity in the region of the patient's wound; however, abnormal activity was present in the right intertrochanteric and right acetabular regions as well as the area overlying the caudal margin of the left hip joint (figure 11A). CT was performed which demonstrated bilateral myositis ossificans (figure 11B). Abnormal soft-tissue uptake may occur before soft-tissue calcification can be seen on plain films.12 CT may be helpful in showing peripheral calcification in a mass when a diagnosis of myositis ossificans is considered.

Abnormal soft tissue uptake is noted in the gluteal region and lateral abdomen (figure 12), which proved to be secondary to rhabdomyolysis in a heroin addict who was reportedly unconscious and in the lateral decubitus position for three days. Renal failure developed due to the extreme severity of the rhabdomyolysis.

Another patient presented with chronic wrist pain in the ulnar-carpal joint space region. Plain films were normal; however, as the patient's symptoms persisted, a bone scan was performed which showed abnormal accumulation in the exact location of the patient's pain (figure 13). At surgery, a triangular fibrocartilage tear was identified. Similar findings can be seen in the knee with tears, especially in those of the medial and lateral-collateral ligaments.

Other causes of diffuse uptake in multiple muscles is related to traumatic or nontraumatic rhabdomyolysis, alcohol abuse, injections, ischemia, radiation, amyloidosis, dermatomyositis, polymyositis, hyperparathyroidism, and renal failure.13

Infection

Abnormal radionuclide activity also can be seen at sites of abscess or infection and is likely related to alterations in capillary permeability and hyperemia.14 The patterns of uptake may vary depending on the amount of tissue involved.

An abnormal periarticular focus of increased uptake in the third digit of Tc-99m-MDP was present in a patient with a normal radiograph of the hand who complained of pain (figure 14). At surgery, a septic joint with an inflammatory synovitis was present. A second patient, this one with bilateral Staphylococcus aureus pneumonia, was evaluated with total bone imaging to detect sites of osteomyelitis (figure 15) in which the bilateral lung infiltrates caused accumulation of Tc-99m-MDP. Diffuse lung uptake also has been reported in patients with other infectious pulmonary processes, such as Pneumocystis carinii pneumonia.15

Vascular

Vascular disease can cause an abnormal increase in radionuclide activity ranging from calcification within the vessel walls to calcified thrombus, or it can be secondary to ischemic effects.16,17

A patient with known lung carcinoma complained of chest pain and was evaluated for thoracic bone involvement. Abnormal accumulation of the radionuclide was present in the right upper lobe neoplasm as well as in an acute myocardial infarct (figure 16). Unstable angina also can cause accumulation of the radiotracer.7

Conclusion

Soft-tissue uptake of bone-seeking radiopharmaceuticals is commonly encountered and the etiologies are many (table 1).

The most common causes of soft-tissue uptake is activity at the injection site (figure 10) or urine in the groin region (figure 11A). Once these or other causes, such as film processing errors (figure 17), have been excluded, careful physical examination of the patient and a good clinical history often result in a short differential diagnosis, and an appropriate recommendation for further imaging studies, if needed. AR

Acknowledgment

The authors would like to thank Dave McGrath for his assistance in preparing this article.

References

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