Uptake Of Tc-99m Methylene Diphosphonate Research Articles

Extraosseous Tc-99m MDP uptake: a pathophysiologic approach.

Scintigraphy with technetium-99m methylene diphosphonate (MDP) delineates a wide spectrum of nonosseous disorders. Neoplastic, hormonal, inflammatory, ischemic, traumatic, excretory, and artifactual entities demonstrate abnormal soft-tissue uptake of Tc-99m MDP. Mechanisms leading to increased extraosseous Tc-99m MDP uptake include extracellular fluid expansion, enhanced regional vascularity and permeability, and elevated tissue calcium concentration. The composition of the calcium deposition and the presence of other metallic ions (eg, iron and magnesium) are important. Soft-tissue Tc-99m MDP uptake is seen in benign (tumoral calcinosis, myositis ossificans) and malignant (sarcomas, adenocarcinomas, metastases) neoplastic entities. Hormonal disturbances in calcium metabolism, especially in hyperparathyroidism, can lead to metastatic calcification, visualized with Tc-99m MDP scintigraphy. Tissue damage from inflammation, infection, or physical trauma results in localized hyperemia, edema, or calcium (and hemosiderin) deposition based on their pathophysiologic characteristics. Urinary tract obstruction, anomalies, or dysfunction are demonstrated by Tc-99m MDP imaging. Common artifacts are related to faulty radiopharmaceutical preparation, Tc-99m MDP administration, and imaging technique. Recognition of these modes of extraskeletal Tc-99m MDP uptake can enhance the diagnostic value of bone scintigraphy.

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.

The investigation of osteoradionecrosis of the mandible by 99mTc-methylene diphosphonate radionuclide bone scans

The need for a reliable non-invasive investigation in osteoradionecrosis (ORN) of the mandible is discussed. The results of 99mTc-methylene diphosphonate bone scans using single photon emission tomography, and measuring dynamic uptake in 13 patients are presented. These suggest that sites of osteoradionecrosis may be defined by a paradoxically increased uptake of 99mTc-methylene diphosphonate.

Gallium-67 uptake in fibrous dysplasia of the bone

In a 43-year-old woman with fibrous dysplasia of the ribs and facial bone and in a 40-year-old man with fibrous dysplasia of the facial bone, there were considerable increases in the uptake of Tc-99m methylenediphosphonate (Tc-99m MDP) and Gallium-67 citrate. Fibrous dysplasia should be added to differential diagnosis of high Gallium-67 citrate uptake in the bone lesions.

Experimental study of vascularized bone: quantitative analysis of bone scintigraphy and histology.

The purpose of this study was the sequential evaluation of vascularized bone by quantitative analysis of bone scintigraphy with Tc-99m methylene diphosphonate (MDP). The correlation between the uptake of Tc-99m MDP and the morphologic behavior of vascularized bone was investigated, simultaneously with bone labeling, contact microradiogram (CMR), and histology of an undecalcified sample. In this experiment, 41 adult female rabbits were used. An island tibia pedicled with the popliteal vessels was used as the model of vascularized bone. The maximum uptake of Tc-99m MDP was observed at two to four postoperative weeks. When bone marrow was partially exposed, the uptake was significantly large. On the basis of this experimental study, the degree of Tc-99m MDP uptake seemed to depend primarily on the osteoblastic activity of vascularized bone. The newly-formed bone was observed mainly at periosteal sites.

Radiopharmacological profiles of tracers under pathophysiological conditions. 99mTc-methylene diphosphonate uptake by bone in altered thyroid status

The uptake of 99mTc-MDP, a skeletal radiotracer, was studied at early and late (3 h) time intervals in rats induced with altered thyroid status. Thyroid dysfunction resulted in disturbances in bone mineral metabolism. Rats rendered hypothyroid showed an overall retardation in growth and also considerably reduced skeletal uptake, especially at early time periods. On the other hand, rats rendered hyperthyroid did not show any significant alteration of the skeletal uptake as compared with controls despite enhanced bone turnover normally observed in hyperthyroidism.

Osteomyelitis and soft-tissue infection: differential diagnosis with 24 hour/4 hour ratio of Tc-99m MDP uptake.

The lesion-to-nonlesion 24 hour/4 hour ratio of technetium-99m methylene diphosphonate (MDP) uptake was used to distinguish osteomyelitis from increased bone uptake caused by adjacent soft-tissue infection. In a prospective study, this ratio was measured in 38 patients with 41 sites of increased uptake that were suspected to be osteomyelitis. The mean ratio was 1.18 +/- 0.18 in patients with proved osteomyelitis, which was significantly higher (P less than .001) than that in patients with increased uptake resulting from soft-tissue infection (0.98 +/- 0.05). On the basis of a receiver operating characteristic curve, a ratio of 1.06 was selected as the cutoff for differentiating osteomyelitis from soft-tissue infection. This method resulted in a sensitivity of 82%, a specificity of 92%, and an accuracy of 85%, and it appears to be more reliable than three- and four-phase scintigraphy, which are subjective and nonquantitative techniques.

Immobilization-induced Hypercalcemia and Regional Osteoporosis

Immobilization hypercalcemia accompanied by unusual hormonal and bony changes complicated the Guillain-Barré syndrome in a 21-year-old woman. Metaphyseal rarefaction appeared in many sites and was severe in the lower limbs. A bone scan showed increased uptake of 99mTc methylene diphosphonate at these sites and throughout the axial skeleton. The literature on experimental metaphyseal rarefaction suggests that osteoclastic resorption and enhanced regional blood flow are associated with immobilization. Suppression of this osteoclastic component of the increased bone turnover, especially if it is widespread, was the rationale for treatment with calcitonin (CT). The patient also became amenorrheic, with low plasma gonadotropin and estrogen levels. Estrogen therapy coincided with a return of plasma calcium to normal.

Estimation of parameters affecting the uptake of 99mTc-methylenediphosphonate in rat femur with model simulation.

The uptake of 99mTc-methylenediphosphonate (MDP) in different parts of rat femur was simulated using a local three-space model for tracer transfer. The model consisted of bone blood, bone ECF-space and space for tracer deposition. The measured 99mTc-MDP concentration in the systemic blood and the local bone blood flow measured by 131I-macroaggregated albumin microspheres were used as input parameters. The measured blood flow values were 6.3, 3.1 and 15.3 ml/100 g/min for proximal, middle and distal femur, respectively. The model parameters that gave the best fit to measured 99mTc-MDP uptake curves in computer simulation showed that bone blood flow, volume of ECF-space, permeability surface area product and accretion constant from ECF-space to space for tracer deposition were highest in distal and lowest in middle femur. The values corresponded to peak extraction fractions of 0.38, 0.62, and 0.31 for proximal, middle and distal femur, respectively. We conclude that the simulation gives acceptable model parameters, and indicates applicability of a similar model into clinical quantitative bone scintigraphy.

Changes in renal uptake of Tc-99m methylene diphosphonate (MDP) in stone-forming rats.

A pyridoxine (vitamin B6)-deficient diet in rats was used as a model of early renal lithiasis to find out if "stone-formers" could be identified from control animals by differences in the biodistribution of Tc-99m MDP. The mean renal uptake of this agent at 3 hours was about 70% higher in test animals than in controls, but there was considerable overlap between the upper limits of the normal range and lower values in "stone-formers." If these results were valid for humans, the metabolic abnormality in males with early stone-forming disease could not be identified with certainty by in vivo measurements of Tc-99m MDP renal uptake alone. However, the skeletal uptake of MDP in the "stone-forming" animals was depressed by 28 to 35%, compared with control rats. Consequently, the renal to skeletal MDP concentration ratio was invariably elevated in "stone-formers" beyond the 95 percentile normal range. Unexpectedly, 76% of the pyridoxine-deficient animals had a higher accumulation of MDP in the myocardium than the upper limit of the normal range. The pyridoxine-deficient diet induced no remarkable early changes in the biodistribution or renal clearance of I-131 Hippuran.

99mTc-MDP uptake in mediastinal hemangioma

Mediastinal hemangioma is a rare disorder. Hemangioma is most commonly seen in subcutaneous tissues. A new case of mediastinal hemangioma is presented and 82 previously reported cases of benign vascular tumors of the mediastinum are reviewed. Uptake of 99mTc-methylene diphosphonate (99mTc-MDP) in this lesion has to the authors' knowledge not been previously reported. A case of hemangioma of the mediastinum which showed significant uptake of 99mTc-MDP is described.

The role of skeletal blood flow in determining the uptake of 99mTc-methylene diphosphonate.

The increased uptake of bone-seeking radionuclides following a fracture has been stated to be due to an increase in bone blood flow, resulting in an increase in capillary surface area available for exchange. This paper examines the relationship between the maximum instantaneous extraction of 99mTc-MDP and blood flow in normal canine tibia. The findings, consistent with the model of capillary action proposed for muscle by Renkin and Crone, are applicable to bone. There is no evidence that in normal bone the surface area available for exchange responds to an increase in bone blood flow.

Experimental drug-induced changes in renal function and biodistribution of 99mTc-MDP.

Increased renal uptake of 99mTc methylene diphosphonate (MDP) was observed irregularly in rats after methotrexate, vincristine or gentamicin, administered separately. Cisplatin regularly induced a dose-related increased MDP uptake which correlated with the degree of tubular damage histologically. The augmented MDP renal uptake was not consistently accompanied by a decreased clearance of simultaneously injected I-131 Hippuran, particularly at lower drug dose levels. This observation agreed with previous evidence that the mechanisms of tubular transport of diphosphonates and organic acids like Hippuran are different. At higher dose levels, the augmented MDP uptake was accompanied by increased renal calcium, hypophosphatemia, elevated serum urea nitrogen and creatinine, and only occasional, mild hypercalcemia. The magnitude of the increased renal uptake of MDP observed could not be explained by alterations in iron metabolism or by dehydration. Drug-induced renal retention of MDP by a factor of 2 or more above normal appears to be a useful indicator of tubular damage when other parameters of renal function are sometimes normal.

Blood flow and bone uptake of 99mTc-labeled methylene diphosphonate.

In mature dogs with comparable levels of bone remodeling, we produced either increased (with adenosine triphosphate) or decreased (with epinephrine) blood flow to one hindlimb. In 13 dogs (five control, four with increased flow, and four with decreased flow), we compared uptake, at 3 h after injection of radiolabeled diphosphonate in the mid-tibia, with blood flow as determined by microspheres. Blood flow was determined with 85Sr-labeled microspheres, and determination of uptake of 99mTc methylene diphosphonate (99mTc-MDP) was by a gamma detector. There was a linear relationship between changes in diphosphonate uptake and changes in blood flow at decreased and normal flows; however, at high flows the relationship was nonproportional, indicating a disproportionately slower increase in 99mTc-MDP uptake with increasing blood flow. In six dogs an initial 1-h uptake curve of 99mTc-MDP was determined in both control and experimental limbs under states of increased and decreased blood flow. The 30-min uptake value, 60-min uptake value, area under the curve, and the slope of the curve were related to flow as determined by microspheres. The data are consistent with the hypothesis that deposition of bone-concentrating isotopes such as 99mTc-MDP is partly controlled by blood flow; at supranormal and normal flows tracer uptake is closely related to blood flow, but at supranormal flow rates it is not and appears to be diffusion limited.

99mTc-Methylene diphosphonate uptake in a primary Wilms' tumor

A report is presented of a patient with primary Wilms' tumor. There was avid retention of 99mTc-methylene diphosphonate in the tumor.

Uptake and localization of 99mTc-methylene diphosphonate in mouse osteosarcoma.

The localization of 99mTc-methylene diphosphonate (99mTc-MDP) in mouse osteosarcoma was studied using a skeletal scintigraphic method and macro- and microautoradiographic methods. On the skeletal scintigraph, the tumor showed a high uptake of 99mTc-MDP and its concentration was about 20 times as high as the value seen in the muscular tissue. The macroautoradiography showed high activity in the tumor bone region and little activity in the nonossified region. On the microautoradiography, the activity of 99mTc-MDP was localized in the mineralized matrix of tumor bone and was almost nil in the nonmineralized matrix (osteoid) and the tumor cells. These findings indicate that the mineralization of the tumor bone matrix plays an important role in 99mTc-MDP uptake in osteosarcoma.

The uptake of 99mtechnetium diphosphonate into degenerating and regenerating muscle : A correlative histological and biochemical study

The uptake of 99mTc-methylene diphosphonate into rat skeletal muscle has been studied. Uptake did not occur in normal or denervated muscles. Muscles damaged by exposure to the myotoxin notexin did accumulate label. The toxin causes a severe inflammatory, necrotising myopathy and regeneration normally begins 2–3 days after toxin administration. The uptake of label was maximal at 12–24 h, at which time muscle wet weight and cellular infiltration were also maximal. Label was found in the muscle mitochondria, the invading inflammatory cells and the oedema fluid. Regenerating muscles did not accumulate label. The uptake of label was positively correlated with total muscle calcium up to 24 h after the onset of necrosis, but it was suggested that the changes in the two parameters are not causally related.

Uptake of 99mTc-Methylene Diphosphonate in Squamous Cell Carcinoma of the Penis

LUNIA, SHANTILAL M.D.; CHANDRAMOULY, BELUR S. M.D.; CHODOS, ROBERT B. M.D.; DAPOLITO, JOHN A. M.S., C.H.P. Author Information

Uptake of 99mTc-Methylene Diphosphonate in a Case of Extraskeletal Ewing???s Sarcoma

From the Department of Radiology, Tufts University School of Medicine, Newton-Wellesley Hospital, Newton Lower Falls, Massachusetts

Localization of 99mTc-Methylene Diphosphonate in Skin Lesions of Pseudoxanthoma Elasticum

Increased uptake of 99mTc-methylene diphosphonate (MDP) is demonstrated in a patient with pseudoxanthoma elasticum (PXE) at the affected site. PXE is a hereditary disease with variable expression. Calification of dermal elastic fibers is a characteristic feature of affected skin. Recently, apatite crystals were identified in the affected skin of the patients with PXE. The mechanism of uptake of 99mTc-MDP is probably related to chemisorption of the tracer onto hydroxyapatite crystals in the affected dermis.