Quantitative studies of bone in postmenopausal women using (18)F-fluoride and (99m)Tc-methylene diphosphonate.

Quantitative radionuclide studies of bone using the short-lived tracers (18)F-fluoride and (99m)Tc-methylene diphosphonate (MDP) are an alternative method to biochemical markers of bone turnover for investigating the dynamic state of the skeleton. In this study we evaluated their use to quantify bone turnover in women receiving antiresorptive therapy compared with that of untreated control subjects. METHODS: The patients were 69 healthy postmenopausal women. Twenty-six women were receiving hormone replacement therapy (HRT) and 43 were untreated age-matched control subjects. After bolus injection of (18)F-fluoride (1 MBq), (99m)Tc-MDP (1 MBq), (51)Cr-ethylenediaminetetraacetic acid (3 MBq), and (125)I-labeled human serum albumin (0.25 MBq), multiple blood samples and urine collections were taken between 0 and 4 h. The clearance to bone mineral K(bone) was first evaluated using the area under the plasma concentration curve (AUC) on the assumption that the rate constant k(4) for the outflow of tracer from bone was negligibly small. AUC values of K(bone) were then compared with those found using a compartmental model method that allowed k(4) to be fitted as a free parameter. RESULTS: Using the AUC method the mean plus minus SD for K(bone) for the 2 tracers were: (18)F-fluoride, 61.8 plus minus 12.0 mL center dot min(-1) (HRT group) versus 67.2 plus minus 12.6 mL center dot min(-1) (control group) (P = 0.045); and (99m)Tc-MDP, 40.3 plus minus 8.2 mL center dot min(-1) (HRT group) versus 44.2 plus minus 7.6 mL center dot min(-1) (control group) (P = 0.024). Values for the 2 tracers in individual patients were moderately well correlated (r = 0.76; P < 0.001). Using the compartmental model method, k(4) for (18)F-fluoride was shown to lie in the range 0--0.0025 min(-1) with a best-fit value of 0.0018 min(-1). Values of K(bone) determined using k(4) = 0.0018 min(-1) were highly correlated with the AUC values (r = 0.989; SEE = 2.05 mL center dot min(-1)) with numeric values that were larger by a factor of 1.53. Analysis of the (99m)Tc-MDP data was more difficult because of uncertainties in protein binding in the extracellular fluid compartment space. The best fit for k(4) was in the range 0.0010--0.0014 min(-1) with values of K(bone) similar to those found using the AUC method. CONCLUSION: Values of K(bone) determined using the AUC method were able to differentiate between HRT-treated women and postmenopausal women who were not treated and were highly correlated with those determined using a compartmental model method with nonzero values of k(4).     

Severe systemic reaction to (99m)Tc-methylene diphosphonate: a case report

We report an unusual severe systemic reaction that occurred in a woman after a (99m)Tc-methylene diphosphonate bone scan and for which no alternative explanation could be found. The bone scintigram showed diffusely increased uptake in the liver and kidneys accompanied by reversible dysfunction of these organs and dermatologic manifestations. We speculate that an immune-mediated mechanism may have caused this unusual reaction.     

Quantitative studies of bone using (18)F-fluoride and (99m)Tc-methylene diphosphonate: evaluation of renal and whole-blood kinetics

We report a study of the renal and whole-blood kinetics of (18)F-fluoride and (99m)Tc-methylene diphosphonate ((99m)Tc-MDP) and their effect on the evaluation of the skeletal kinetics of the two bone tracers. Data were obtained during an investigation of postmenopausal women taking hormone replacement therapy who were compared with untreated, age-matched controls. After intravenous injection of 18F-fluoride (1 MBq), (99m)Tc-MDP (1 MBq), (51)Cr-ethylenediaminetetraacetic acid (51Cr-EDTA) (3 MBq) and (125)I-human serum albumin ((125)I-HSA) (0.25 MBq), multiple blood samples and urine collections were taken between 0 and 4 h after injection. (51)Cr-EDTA data were used to evaluate the glomerular filtration rate (GFR) and the completeness of each timed urine collection. (125)I-HSA data were used to evaluate the plasma volume and the red cell uptake of the other three tracers. At 4 h, the cumulative urine excretions (and standard deviations, SDs) were: (99m)Tc-MDP, 58.2% (4.8%); (18)F-fluoride, 36.1% (5.7%); (51)Cr-EDTA, 81.5% (4.5%). Plots of the renal clearance of (18)F-fluoride against urine volume showed that urine flow rates greater than 5 ml.min-1 were necessary to ensure a constant renal clearance of (18)F and hence stable conditions for the evaluation of bone tracer kinetics. In contrast, a low urine flow rate had no effect on the renal kinetics of (99m)Tc-MDP. For MDP, the evaluation of skeletal kinetics requires data on protein binding so that calculations can be performed for free MDP. In the present study, protein binding of MDP was evaluated from the ratio of total (99m)Tc-MDP renal clearance to GFR based on the principle that free (99m)Tc-MDP is a GFR tracer. Between 0 and 4 h after injection, the fractional protein binding of MDP increased linearly with time, changing from 21+/-5% immediately after injection to 58+/-5% at 4 h. Although red cell uptake of (99m)Tc-MDP was negligible, for (18)F-fluoride around 30% of circulating tracer was transported in red cells. In view of the data showing the rapid transport of (18)F-fluoride across the red cell membrane, bone kinetic data for (18)F are more accurately reported as whole-blood clearance rather than plasma clearance.     

Tc-99m dicarboxypropane diphosphonate uptake in ovarian fibrothecoma

A 76-year-old woman had a palpable mass in the lower abdomen. Computed tomography showed an abnormal pelvic mass with necrotic areas, probably of ovarian origin. A Tc-99m dicarboxypropane diphosphonate whole-body scan performed to evaluate the extent of the disease (i.e., the presence of bone metastases) revealed only diffuse uptake of the tracer in the pelvis. Histopathologic analysis after surgical excision of the mass revealed a fibrothecoma of the right ovary, which is a benign tumor composed of cells derived from the ovarian stroma and, in some instances, resembles the thecal element of the follicle.     

Hepatic uptake of technetium-99m diphosphonate in thalassemia major

Two cases of thalassemia major are presented in which bone scintigraphy demonstrated diffuse hepatic uptake of Tc-99m diphosphonate. Although abnormal splenic and renal uptake of Tc-99m phosphates has been reported in patients with thalassemia major, hepatic uptake has not been reported previously. This scintigraphic finding is presumably due to increased iron deposition in the liver, resulting from increased iron turnover and retention in these patients and from multiple previous blood transfusions.     

Comparison of (18)F-FDG PET/CT and (99 m)Tc-MDP bone scintigraphy for detection of bone metastasis in osteosarcoma

Objective

We compared the diagnostic performance of (18)F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) and (99 m)Tc-methylene diphosphonate bone scintigraphy (BS) for the detection of bone metastasis in osteosarcoma.

Materials and methods

We retrospectively reviewed 206 patients with stage II–IV osteosarcoma treated with surgery and chemotherapy as well as at least one paired PET/CT and BS scan (defined as an examination). PET/CT and BS images were interpreted separately. When analyzing the diagnostic yield of a combination of PET/CT and BS (PET/CT+BS), an examination was considered positive if either PET/CT or BS scored positive. The final diagnosis was obtained from histological findings or clinical follow-up with imaging studies for at least 6 months. Diagnostic performances of PET/CT, BS, and their combinations were calculated.

Results

Out of 833 examinations in 206 patients, 55 with 101 lesions in 38 patients were confirmed as bone metastases. The sensitivity, specificity, and diagnostic accuracy were 95, 98, and 98 %, respectively, for PET/CT; 76, 97, and 96 %, respectively, for BS; and 100, 96, and 97 %, respectively, for PET/CT+BS in an examination-based analysis. Lesion-based analysis demonstrated that the sensitivity of PET/CT+BS (100 %) was significantly higher than that of PET/CT (92 %) or BS (74 %) alone. BS detected significantly less bone metastases in the growth plate region than outside the growth plate region (22 vs. 77 %).

Conclusions

PET/CT is more sensitive and accurate than BS for diagnosing bone metastases in osteosarcoma. The combined use of PET/CT and BS improves sensitivity.     

Splenic uptake of both technetium-99m diphosphonate and technetium-99m sulfur colloid in sickle cell beta (0) thalassemia

A 19-year-old black woman with sickle cell beta(0) thalassemia had experienced more than 100 hospital admissions for sickle cell crisis and aseptic necrosis of both femoral heads. Her spleen was enlarged threefold and accumulated both radiocolloid and bone-seeking agent on two occasions, demonstrating an exception to the rule in sickle cell anemia that spleens that take up bone-seeking agents demonstrate functional asplenia. In the context of fever, left upper quadrant pain, and splenomegaly, the pattern of calcification in the patient's spleen as revealed in ultrasound and CT studies suggested possible abscess and led to unnecessary splenectomy. The nuclear medicine studies did not support this diagnosis. Nuclear medicine physicians should not be misled by splenic findings of sickle cell thalassemia (and possibly of other heterozygous sickle cell disorders) that differ from those of the more familiar homozygous sickle cell anemia.     

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.     

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.     

Idiopathic hepatic uptake of (99m)Tc methylene diphosphonate: a case report

OBJECTIVE: Two sequential (99m)Tc methylene diphosphonate (MDP) scans were performed on a 42-y-old woman with insulin-dependent diabetes mellitus, chronic right pyelonephritis and anemia. The initial scan showed reduced skeletal uptake with intense and diffuse hepatic uptake. Because these findings were similar to those seen when excessive hydrolyzed-reduced (99m)Tc colloids are present in the radiopharmaceutical, the scan was repeated after an adequate time delay. Increased skeletal uptake was evident in the second scan, but the hepatic uptake persisted. Although there are numerous causes of soft tissue activity on (99m)Tc MDP bone scans, the responsible pathologic entity is not always clear. This study reviews several possible reasons for such uptake, although the exact mechanism in this case remains conjectural.     

Abnormal uptake of Technetium-99 m hydroxymethylene diphosphonate in the liver

Diffuse liver uptake on bone scintigraphy is a rare occurrence with only a few reports in the literature. A case of diffusely increased uptake in a patient with acute hepatitis is presented.     

Persistent F-18 deoxyglucose and Tc-99m methylene diphosphonate uptake in a lower extremity radiation port

Four years after radiation therapy to the lower extremity for a bone metastasis, persistent F-18 FDG and Tc99m MDP uptake were noted in the radiation port. Presumably ongoing inflammatory cellular processes accounts for this finding.     

Isolated ectopic lung uptake of technetium 99m methylene diphosphonate on bone scintigraphy in primary amyloidosis

Pulmonary deposition of technetium 99m methylene diphosphonate was found on a bone scan of a patient with undiagnosed primary AL amyloidosis. Unusual clinical manifestations during the course of the disease led to a post-mortem diagnosis. The mechanisms for pulmonary and other ectopic soft tissue bone scan tracer depositions, as well as their significance in the diagnosis of amyloidosis, are discussed.     

Multifactorial uptake of Tc-99m methylene diphosphonate in chronic renal failure

Soft-tissue calcifications are a frequent complication in patients with chronic renal failure. Numerous underlying factors are thought to favor their formation. A case is presented of a patient who was in end-stage renal failure, secondary to glomerulonephritis. A renal transplant had not been successful. She was on long-term dialysis and had suffered aluminum toxicity (positive desferrioxamine test). She complained of proximal myopathy and bone pain.     

Clinical significance of technetium-99m methylene diphosphonate myocardial uptake: association with carcinoma of the prostate

Benign myocardial uptake of technetium-99m labelled phosphates, not related to cardiac or metabolic disorders, has been documented except in the case of^99mTc-methylene diphosphonate (MDP). The aim of this study was to assess the frequency of myocardial uptake and its possible association with malignant tumours in general and prostatic carcinoma in particular. We reviewed bone scintigrams performed with either^99mTc-hydroxydiphosphonate (HDP) or^99mTc-MDP over a period of more than 2 years for all patients with prostatic carcinoma and a matching group of patients suffering from other malignant and non-malignant disorders. A total of 965 scintigrams of 812 patients (males=559, females=253; age range 50–91 years, average age 69.2 years) were reviewed. Increased myocardial uptake was detected in 19 scintigrams (MDP=13, HDP=6) of 18 patients (17 males, one female). Most of the male patients with increased myocardial uptake had prostatic carcinoma (13/17) and were over 80 years of age (12/17). All patients were free of any cardiac or noncardiac disorder that might account for such uptake. When scintigraphy was repeated in the same patient, the uptake of^99mTc-HDP was more diffuse and of higher grade than that of^99mTc-MDP Benign myocardial uptake of^99mTc-MDP is more common than previously thought. Although uptake of radiophosphates is attributed to asymptomatic atherosclerotic changes associated with old age, a strong association with prostatic carcinoma exists which may indicate variations in the bone: soft tissue affinity of different MDP complexes.