Idiopathic Hepatic and Splenic Uptake of ^99mTc-Methylene Diphosphonate

A 67-year-old man, with type II diabetes mellitus for 25 years and hypertension for 15 years (on regular medication), biopsy-proven case of carcinoma prostate, was referred for bone scintigraphy to rule out the possibility of bone metastasis. He presented with complaints of low backache and swelling associated with pain in the left ankle for 2 months. The previous bone scintigraphy revealed increased osteoblastic activity at bilateral acetabulum and left ischium – metastatic. Ultrasonography of the abdomen and pelvis revealed Grade II prostatomegaly. Magnetic resonance imaging pelvis revealed features suggestive of carcinoma prostate with bony metastasis. The patient is on hormonal therapy for the past 1 year with no history of chemotherapy or radiotherapy. Biochemical investigations such as serum electrolyte, calcium, phosphate, creatinine, lactate dehydrogenase, and alkaline phosphate levels were in the normal limit during both the initial and repeat bone scans. The bone scan revealed diffuse and intense tracer uptake in the liver and, to a lesser degree, in the spleen. Relatively decreased skeletal uptake on the bone scan was also observed with foci of increased radiopharmaceutical uptake in the left pubic bone and the left side of the mandible [Figure 1].

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Figure 1 Single-photon emission computerized tomography/computed tomography image of the pelvic region revealing osteoblastic lesion in the superior rami of the pubic bone with subtle sclerotic changes

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Single-photon emission computerized tomography/computed tomography ( SPECT/CT) of the pelvic region revealed increased radiopharmaceutical uptake in the superior rami of the left pubic bone with subtle sclerotic changes on low-dose CT. The bone scan of other patients done on the same day did not reveal such abnormal nonosseous tracer uptake.

A repeat bone scintigraphy with SPECT/CT of the pelvic region was performed 1 month later. There was considerably more skeletal uptake, and hepatic and splenic radiopharmaceutical localization was absent. Tc-^99m-methylene diphosphonate (MDP) bone scintigraphy is routinely performed nuclear medicine procedure in the workup of a patient with carcinoma.[1] Increased radiopharmaceutical uptake is seen in lesions having increased osteoblastic activity. Due to urinary excretion of Tc-99m-MDP radiopharmaceutical, kidneys and urinary bladder are generally visualized [Figure 2].

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Figure 2 (a) Whole-body planar images (day-1) revealing diffuse hepatic and splenic uptake, (b) Whole-body planar images (day-2) revealing no nonosseous uptake of the tracer

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Hepatic and splenic uptake of ^99mTc-MDP is an unusual finding in nuclear medicine practice, occurring less frequently than focal hepatic abnormalities. Table 1 lists several reported causes of diffuse hepatic uptake.[2]

The most common reason in the current clinical scenario is scintigraphic studies involving the use of Tc-99m-tagged colloid radiopharmaceuticals on the previous day to the bone scintigraphic study or misadministration of the radiopharmaceutical like ⁶⁷Ga-citrate or ¹¹¹In-labeled white blood cells. However, the patient did not have any scintigraphic study with radiocolloid on the previous day, and also, misadministration/delayed administration was also excluded. Metastatic calcification in soft tissue is mainly due to hypercalcemia. This can be due to increased secretion of parathormone, Vitamin D-related disorders, renal failure, and/or aluminum toxicity. These causes are ruled out due to normal biochemical profile. Faulty radiopharmaceutical preparations such as the formation of a Tc-99m colloid complex may be the cause of reticuloendothelial tissue uptake.[3]^99mTc colloid may be formed in the presence of excessive aluminum ion or when excessive hydrolyzed-reduced ^99mTc colloid from any cause is present. This radiochemical contaminant will localize in the extraosseous sites such as liver, spleen, or bone marrow if it is present in sufficient quantity in the ^99mTc-MDP. Other causes could be iron overload,[4] iodinated-based or gadolinium contrast study just before bone scintigraphy,[5] and severe hepatic necrosis.[67]

Pathologic changes occur due to change in the normal physiological event. Extraosseous localization of the bone-seeking radiopharmaceuticals in tissues other than kidney and urinary bladder should raise a suspicion of the underlying cause, and pathophysiological basis of pathology should always be kept in mind while interpreting the scan as it may have a tremendous impact on the further management and follow-up of the patient. Recognition of specific mechanisms and appearance of soft-tissue abnormalities on skeletal scintigraphy reduces the possibility of confusion and enhances the diagnostic value of the study.