Different findings in Tc-99m MDP bone scintigraphy of patients with sickle cell disease: report of three cases

Objective Sickle cell anemia is an inherited disorder caused by abnormal hemoglobin, the S hemoglobin. Although vaso-occlusive crises can occur virtually in any organ, they are particularly common in the bony skeleton of affected patients. Bone marrow necrosis, bone infarcts, osteomyelitis, and aseptic necrosis are common complications in patients with sickle cell disease. Beside these abnormalities of the skeletal system, diffuse micro or macro calcification resulting from both splenic infarction and repeated vaso-occlusive episodes in the kidneys can be shown by technetium-99m methylenediphosphonate (Tc-99m MDP) bone scintigraphy. We present here the different osseous and extraosseous abnormalities noted on bone scintigraphies of three patients with sickle cell anemia. Methods Whole-body bone scan was performed after injecting 740 MBq of Tc-99m MDP in three patients with sickle cell disease. Results Tc-99m MDP whole-body image of the first patient showed non-uniform uptake in the anterior and posterior aspects of multiple ribs and bilateral femurs and tibias that was attributed to repetitive infarcts. Additionally, increased activity in shoulders, right elbow, and right knee was consistent with arthritis. Tc-99m MDP image of the second patient demonstrated avascular necrosis of the left femoral head and diffuse activity in the enlarged kidneys. Increased activity in the spleen that was attributed to repetitive infarcts was visualized in bone scan of the third patient. Conclusions In light of the findings in these cases, bone scintigraphy is a reliable imaging method in detecting both osseous and extraosseous abnormalities of sickle cell disease and may be used initially.     

Neuroblastoma: imaging evaluation by sequential Tc-99m MDP, I-131 MIBG, and Ga-67 citrate studies

Fourteen children with histopathologically confirmed neuroblastoma underwent sequential correlative imaging studies using I-131 MIBG, Tc-99m MDP, and Ga-67 citrate during various stages of the disease. Of the patients 86% showed I-131 MIBG accumulation in the primary tumoral site, whereas 71% showed Tc-99m MDP and 79% Ga-67 citrate uptake. In 86% at least one of the two latter radiopharmaceuticals concentrated in the primary tumor. The use of all three radiopharmaceuticals raised the detection rate to 93%. Of the osseous or extraosseous metastases 100% were detected by Tc-99m MDP studies. The I-131 MIBG studies were positive in 71% of the osseous metastases and in 70% of the extraosseous metastases. No Ga-67 citrate uptake was demonstrated in osseous metastases, although one extraosseous lung metastasis concentrated this radiopharmaceutical. Tc-99m MDP bone imaging was the best method for diagnosing metastatic spread of the disease and for monitoring the results of treatment. Primary tumor uptake was best indicated by I-131 MIBG. Both Ga-67 citrate and I-131 MIBG were superior to Tc-99m MDP with regard to accurately demonstrating the extent of primary tumors. Only Tc-99m MDP indicated the relationship of these tumors to the kidneys and neighboring osseous structures, providing early screening of kidney compression. Ga-67 citrate study was mainly indicated in tumors with catecholamine depletion, which failed to concentrate the other two radiopharmaceuticals. I-131 MIBG proved especially useful in detecting neuroblastoma with negative Tc-99m MDP and Ga-67 citrate studies and also proved to be helpful with those cases in which I-131 MIBG was planned for therapy. The following strategy is suggested for evaluating neuroblastoma.(ABSTRACT TRUNCATED AT 250 WORDS)     

Poor accumulation of technetium-99m glucoheptonate in sarcoidosis and other diffuse infiltrative lung diseases as compared with gallium-67 citrate

Forty-two patients with diffuse infiltrative lung diseases were imaged with Ga-67 citrate and Tc-99m glucoheptonate (GH). Twenty patients had sarcoidosis, six had fibrosis, six had tuberculosis, nine had lung infiltration, and one had pleural empyema. The main difference between Ga-67 and Tc-99m GH was the much greater uptake of Ga-67 in sarcoidosis than that of Tc-99m GH. Fifteen patients with sarcoidosis had positive Ga-67 scans but only six had positive Tc-99m GH scans. The results in other diffuse infiltrative lung diseases were almost equal with Ga-67 and Tc-99m GH. Although Tc-99m GH is less expensive and simpler to use, it is not an adequate substitute for Ga-67 in diffuse infiltrative lung diseases.     

Detectability of metastatic bone tumor by Ga-67 scintigraphy

Ga-67 scintigrams in patients with malignant diseases sometimes reveal uptake of the tracer in the bone metastases. Detectability of Ga-67 scintigraphy for metastatic bone tumors and benign bone lesions was compared with that of Tc-99m bone scintigraphy. Countable bone metastases detected by bone scintigraphy were evaluated whether the lesion showed apparent, faint, or negative Ga-67 uptake. Of 47 lesions 23 (49%) showed apparent uptake and 17 (36%) showed negative uptake. On the other hand, of 71 benign bone lesions, only 7 (10%), mostly fracture/osteotomy, showed apparent uptake of the tracer. Uptake in the other benign lesions such as trauma of the ribs, spondylosis deformans, and arthrosis deformans was rather faint. In patients with multiple bone metastases, 9 patients (82%) out of 11 showed more prominent abnormal findings in Tc-99m MDP bone scintigraphy than in Ga-67 scintigraphy; that is, Ga-67 scintigraphy was not able to reveal all metastatic bone lesions. In patients with untreated or recurrent tumors, relation between Ga-67 uptake in the tumors and that in the bone metastases was evaluated. Of 7 patients with negative Ga-67 uptake in the primary tumors, 5 showed positive Ga-67 uptake in the bone metastases; that is, there seemed to be little relation between Ga-67 affinity to the primary tumors and that to the bone metastases. Mechanisms of the Ga-67 uptake in the bone metastases were discussed. Not only the tumor cells or tissues in the bone metastases but also bone mineral or osteoclasts might be the deposition sites of Ga-67.     

Multifocal Pott's disease (tuberculous spondylitis) incidentally detected on Tc-99m MDP bone and Ga-67 citrate scintigraphy in a patient with diabetes

Pott's disease is an uncommon extrapulmonary form of tuberculosis. Delay in diagnosis and management may cause serious complications. The authors describe Pott's disease incidentally detected on Tc-99m MDP bone and Ga-67 imaging in a patient with diabetes. Tc-99m MDP bone scintigraphy showed intensely increased uptake in the lower cervical spine and lumbosacral regions. Ga-67 scintigraphy revealed intensely increased uptake corresponding to the areas noted on Tc-99m MDP bone scintigraphy. Magnetic resonance imaging showed destructive lesions in the C5-C6 and L5-S1 intervertebral discs with destruction of adjacent end plates. Biopsy of the lumbosacral area was guided by computed tomography, and histologic examination of the bone specimen showed caseation, giant cells, and acid-fast bacilli. Posterior decompression and posterolateral spinal fusion with bone grafts were performed. Antituberculous chemotherapy with isoniazid, rifampicin, pyrazinamide, and ethambutol was started. The patient showed remarkable relief of symptoms during a period of 9 months of therapy. Both Tc-99m MDP bone and Ga-67 imaging can offer the convenience of screening the entire body to detect multiple sites of Pott's disease.     

Primary Ewing sarcoma: follow-up with Ga-67 scintigraphy

While avid accumulation of gallium-67 citrate and technetium-99m methylene diphosphonate (MDP) occurs initially in most cases of primary Ewing sarcoma, uptake after therapy is less well defined. Thirty patients with Ewing sarcoma who underwent Ga-67 and bone scintigraphy at diagnosis, at completion of therapy, and at relapse from 1978 to 1988 were evaluated. All 30 patients showed less primary site Ga-67 activity following therapy. Twenty-three of 28 patients who underwent corresponding bone scintigraphy showed less uptake, but residual activity was usually more intense than with Ga-67. Avid reaccumulation of Ga-67 occurred in four of five patients with primary site relapse, while patients who underwent bone scintigraphy showed less change. It was concluded that a greater decrease in Ga-67 than in Tc-99m MDP uptake often occurs in patients successfully treated for primary Ewing sarcoma. Information obtained at Ga-67 scintigraphy is most likely to be helpful if results of bone scintigraphy remain abnormal or if occult relapse is suspected.     

Tc-99m hexamethylpropylene-amine oxine (HM-PAO) uptake in a bone metastasis

Uptake of Tc-99m Hexamethylpropylene-amine Oxine (HM-PAO) was seen in bone metastases from carcinoma of the lung. The uptake was prominent when compared to Tc-99m MDP, I-123 IMP, and Ga-67 citrate. Brain imaging with Tc-99m HM-PAO and N-isopropyl-p-[I-123] iodoamphetamine (IMP) is now frequently performed. Uptake of these agents has been reported in brain tumors and melanomas. In this report, uptake of Tc-99m HM-PAO in a metastatic lesion in bone is discussed.     

Malignant external otitis: the role of computed tomography and radionuclides in evaluation

Nine patients with malignant external otitis (MEO) were evaluated with Tc-99m bone scans, Ga-67 citrate scans, pluridirectional tomography, and computed tomographic (CT) scans in order to assess the role of each in the diagnosis and management of MEO. The Tc-99m and Ga-67 citrate scans were the most accurate studies in the initial identification of disease activity, while the return to normal or improvement of the Ga-67 citrate scan has been shown to correlate best with clinical resolution of MEO. CT demonstrated soft-tissue disease and central skull base osteomyelitis better than pluridirectional tomography. CT is excellent for localizing and following the progression of bone disease; however, because reossification of the skull base is a very slow process, CT cannot be used to follow accurately regression or inactivity of MEO affecting this area. CT is the best modality for following soft-tissue extension of MEO.     

The role of Tc-99m MDP and Ga-67 citrate in predicting the cure of osteomyelitis

Twenty rabbits with chronic osteomyelitis of the tibia were treated for eight weeks and then scanned with Tc-99m MDP and Ga-67 citrate. All were sacrificed and bacteriologic cultures of the tibia were obtained. All rabbits had positive Tc-99m MDP scans at the end of treatment despite thirteen cures of osteomyelitis. Eight had negative gallium scans and negative cultures. Five of the twelve positive gallium scans had negative cultures, while seven had positive cultures. Tc-99m MDP alone is not sensitive enough to be useful in predicting the cure of osteomyelitis, and combining Tc-99m MDP and Ga-67 citrate scintigrams offers no additional information over the Ga-67 citrate scintigram alone in follow-up of osteomyelitis.     

Tc-99m DTPA used as reference imaging to evaluate the distribution of other tumor-seeking tracers in tumors associated with neurofibromatosis.

Two patients with multiple benign and malignant tumors associated with neurofibromatosis underwent radionuclide imaging with Tc-99m DTPA, Tl-201, and Ga-67. In these patients, Tc-99m DTPA accumulated intensively in both the benign and malignant tumors and localized and defined the extent of every tumor. In contrast, Ga-67 and Tl-201 uptake was seen only in focal areas of tumor where there was malignant transformation or at sites that showed progressive tumor growth. Tc-99m DTPA imaging accurately demonstrated areas of neoplastic involvement and identified the areas that would be seen with the other two tracers in individual tumors. Tc-99m DTPA may not always be used for the differential diagnosis of malignant and benign tumors of neurofibromatosis, but it can provide a reference pattern for imaging to evaluate accurately the distribution of Tl-201 and Ga-67 by mapping out the anatomic extent of these tumors.     

Bone and marrow imaging in sickle cell disease: Diagnosis of infarction

Sickling of erythrocytes in patients with S-hemoglobin causes marrow and bone infarction. The former can be demonstrated as a lack of 99mTc-sulfur colloid uptake on marrow imaging examination. These defects may resolve or persist long after the acute episode. If the bone is involved in the acute episode, imaging within the first few days of onset of symptoms can show lack of 99mTc-labeled phosphate uptake, usually in a smaller area than that shown by marrow scanning. Follow-up bone imaging shows increased activity, particularly along the circumference of the bone where periosteal reaction can be demonstrated radiographically. Magnification by use of the pinhole collimator provides better definition of the uptake defect and the distribution of the increased reactive uptake. Timing of examination is important. If marrow imaging is performed in an asymptomatic period, the repeat examination during a painful crisis permits differentiation of old and acute marrow infarction. If 99mTc-phosphate imaging is performed after about 2 days of symptoms, acute infarction can be differentiated from osteomyelitis, which it may mimic clinically. Although osteomyelitis may cause no increased activity in the first 48 hr after onset of symptoms, it is characterized by intense focal activity thereafter (see article by Handmaker in this issue). To assist in differentiating bone infection in a site of marrow infarction demonstrated by marrow imaging, serial bone imaging with magnification may be useful. The uptake defect, followed in several days to 2 weeks, by circumferential increased activity, is a different pattern than the homogeneously intense activity of osteomyelitis, but the peripheral distribution may not be apparent on routine imaging. It is hoped that the utilization of these techniques can decrease the emotional and economic costs of prolonged hospitalization for suspected infection and can also expand our knowledge of the complex pathophysiologic changes of sickle cell bone disease.     

Accumulation of Tc-99m MIBI in breast lymphoma: Comparison with Ga-67 citrate

We report 2 cases of malignant lymphoma of the breast which were clearly shown on total body imaging as well as on SPECT with Ga-67 and Tc-99m MIBI. Tumor accumulation of Ga-67 was seen in all cases including a recurrent tumor. Ga-67 scintigraphy is useful for follow up in detecting relapse, as well as in predicting responses to therapy. Tc-99m MIBI was found to accumulate in the malignant lymphoma of the breast, and especially SPECT images of breast lesions provided better contrast than planar images, and Tc-99m MIBI SPECT could diagnose localization of the tumor because there was no uptake by the breast. But the Tc-99m MIBI accumulation of the tumor was lower than Ga-67.     

Comparative evaluation of technetium-99m glucoheptonate and gallium-67 citrate thoracic imaging in detection of mediastinal and hilar involvement in primary lung cancer

Fifty-two patients with proven primary lung cancer who were referred for mediastinoscopy were prospectively studied with Tc-99m glucoheptonate and Ga-67 citrate thoracic scintigraphy. Primary lung tumors concentrated Ga-67 in 92% of cases, compared to 88% for Tc-99m glucoheptonate. Mediastinoscopy confirmed the presence of mediastinal metastases in 23 patients. The sensitivity of Tc-99m glucoheptonate and Ga-67 scans for mediastinal involvement detection is respectively 52% and 83%, for a specificity of 100% (Tc-99m glucoheptonate) and 88% (Ga-67). Twenty-nine patients underwent thoracotomy after a negative mediastinoscopy. Hilar metastatic involvement was present in eight patients. The sensitivity and the specificity for detection of hilar involvement were respectively 63% and 95% for Tc-99m glucoheptonate and 88% and 78% for Ga-67. Although more specific than Ga-67 scan, Tc-99m glucoheptonate thoracic imaging cannot be recommended in the staging of lung cancer because of its low sensitivity in the detection of intrathoracic metastatic spread of primary lung carcinoma.     

Tl-201 uptake in brown tumors of hyperparathyroidism.

Tl-201 chloride bone scans were performed on nine patients with primary hyperparathyroidism just after Tl-201 and Tc-99m parathyroid subtraction scintigraphy. Bone lesions accumulate Tl-201, especially in sites of brown tumor formation. This was proven by the histopathologic examination of two patients. Eight patients had bone scans with Tc-99m MDP. The lesion-to-background ratio was quantified in seven patients for Tl-201 and in four patients for Tc-99m MDP. Tl-201 uptake of the lesions were quantified in two patients. The lesion-to-background ratio was 1.63 +/- 0.21 and 2.51 +/- 0.88 for Tl-201 and Tc-99m MDP, respectively. A Ga-67 citrate scan was performed on one patient, and the lesion-to-background ratio was 1.49 +/- 0.06. The accumulation of Tl-201 in brown tumors of bone might be due to increased blood flow and local metabolic activity. Tl-201 chloride was inferior to Tc-99m MDP in lesion detection. It is concluded that bone imaging with Tl-201 can easily be performed following parathyroid subtraction scintigraphy to delineate the sites of brown tumor formation.     

Increased bone marrow blood flow in sickle cell anemia demonstrated by thallium-201 and Tc-99m human albumin microspheres

Lower extremity vascularity in nine patients with sickle cell anemia was studied by intra-arterial Tc-99m human albumin microspheres or intravenous thallium 201. In eight patients, the normal pattern of greater muscle than bone activity was reversed with marked tracer localization in skeletal parts usually not visualized. In four cases, there were distinct focal abnormalities in the femurs and tibias which correlated with defects on Tc-99m sulfur colloid marrow scans. Tc-99m pyrophosphate bone scans demonstrated normal uptake in the same areas. The scintigraphic findings indicate a markedly increased relative bone marrow blood flow.     

Technetium-99m white blood cell imaging: false-negative result in salmonella osteomyelitis associated with sickle cell disease

The authors report a case of sickle cell anemia associated osteomyelitis where the Tc-99m white blood cell imaging was negative, and bone imaging showed increased uptake in the region in question. The reasons for the possible false-negative image are discussed.     

Testicular lymphoma with bone/bone marrow metastases illustrated by scrotal sonography, spinal MRI, and total body Tc-99m HMDP and Tc-99m MIBI imagines

An 83-year-old man with testicular lymphoma demonstrated progressive scrotal enlargement with non-homogeneity sonographically and abnormally increased uptake in the scrotum of Tc-99m HMDP and Tc-99m MIBI scintigraphically. Extensive bone/bone marrow metastases were exhibited by Tc-99m MIBI and Tc-99m HMDP scintigraphies and MRI of the spine. In addition, focal/tubular activity of the femoral bone marrow on Tc-99m MIBI imaging was consistent with skeletal scintigraphic findings. It is emphasized that Tc-99m MIBI total body imaging enabled the demonstration of testicular lymphoma as increased uptake and the illustration of skeletal/bone marrow metastases as diffuse and/or focal increased uptake, especially focal/tubular MIBI activity of the femoral marrow.     

Abnormal lung and liver uptake of gallium-67 and technetium-99m MDP in hypercalcemia of lymphoma with metastatic pulmonary calcification

Abnormal pulmonary uptake of Ga-67 citrate and Tc-99m MDP and reversible liver uptake of Tc-99m MDP was seen in a patient with hypercalcemia of lymphoma and biopsy-proven metastatic pulmonary calcification. Abnormal lung uptake of Tc-99m MDP may confirm the diagnosis of pulmonary calcification, lessening the need for invasive procedures to evaluate pathologic lung uptake of Ga-67 citrate.     

Gallium accumulation in marrow lymphocytes

A case of Ga-67 and Tc-99m WBC imaging in a patient is shown in which the discrepancy in the accumulation of the two imaging agents in radiated bone indicates that gallium accumulated predominantly in marrow lymphocytes in the skeleton of this patient.     

Subacute splenic abscess. Appearance on indium-111 leukocyte, gallium-67, and technetium-99m sulfur colloid imaging

A case of a 23-year-old man with an encapsulated, anaerobic splenic abscess is reported. Both the In-111 leukocyte and Tc-99m sulfur colloid scans demonstrated an intrasplenic defect. The Ga-67 citrate scan revealed uptake in the rim of the abscess only where the abscess cavity was relatively photon-deficient. The combined Tc-99m sulfur colloid/In-111 leukocyte/Ga-67 scan appearance of a subacute splenic abscess has not been described previously. In cases suspected to be splenic abscesses the combined In-111 leukocyte/Tc-99m sulfur colloid imaging is the most useful.