Bone imaging using Technetium-99m-methylene diphosphonate is one of the most frequently used studies in nuclear imaging. When non-osseous accumulation of the radionuclide occurs, there are several entities that may be responsible. This presentation reviews the common causes of soft-tissue uptake of Tc-99m-MDP.
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
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
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
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
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.
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
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
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 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
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
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
The authors would like to thank Dave McGrath for his assistance
in preparing this article.
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