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PubMed1994

Joint scintigraphy for quantification of synovitis with 99mTc-labelled human immunoglobulin G compared to late phase scintigraphy with 99mTc-labelled diphosphonate.

The ability of scintigraphy with technetium 99m-labelled polyclonal human immunoglobulin G (99mTc-IgG) to detect and quantify arthritis activity was studied in 24 patients with RA and in 10 patients with OA. The results of 99mTc-IgG scintigraphy were compared with those of scintigraphy with 99mTc-labelled hydroxymethylene-diphosphonate (HDP). The mean joint scores of 99mTc-IgG scintigraphy in RA patients with active disease were significantly higher (P < 0.001) than the mean scores in patients with inactive disease. The mean joint scores were also higher in patients with erosions compared to those in patients without erosions (P < 0.05). For 99mTc-HDP scintigraphy no significant differences were found between the mean joint scores of these patient groups. Comparison of scintigraphic results between patients with RA and OA revealed that the mean joint score of 99mTc-IgG scintigraphy was significantly (P < 0.001) higher in the patients with RA than in patients with OA, whereas for 99mTc-HDP scintigraphy this difference was not significant. These results show that 99mTc-IgG scintigraphy, when compared to 99mTc-HDP scintigraphy, is a more specific method of detecting synovitis and, also, shows differentiation between different degrees of arthritis activity in RA.

Adult↗
PubMedDate not supplied

Assessment of the in vitro transport parameters for ethanehydroxy diphosphonate through a polyurethane membrane. A potential refillable reservoir drug delivery device.

Calcification (CALC) is the most frequent cause of failure in bioprosthetic heart valves (BHV) fabricated from glutaraldehyde pretreated porcine aortic valve or bovine pericardium. Site specific controlled administration of ethanehydroxy diphosphonate (EHDP), using numerous carriers, has been successful in inhibiting CALC of BHV tissue in an accelerated rat subdermal model, without adverse effects on serum calcium, bone development, or overall somatic growth. The current study was designed to evaluate refillable reservoir devices fabricated from polyurethane (Biomer Woburn, MA) with regard to their transport properties relative to EHDP. The refillable reservoirs were evaluated for EHDP release in vitro at 22 degrees C (under perfect sink conditions) into both a physiologic receptor phase (N-2 hydroxyethylpiperazine-N'-2-ethanesulfonic acid buffer, pH = 7.4) with (1.5 mM) or without Ca2+ present. Transport parameters for EHDP diffusion through the polyurethane membranes used to fabricate the reservoirs were significantly different for the two receptor phases evaluated. The mean diffusion coefficients (D) for EHDP through the polyurethane membrane into each receptor phase were not significantly different. However, an approximately 3.5-fold reduction was observed in the mean value of the partition coefficient (K) for EHDP when EHDP was evaluated for release into a receptor phase that contained 1.5 mM Ca2+.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1979

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.

Adult↗
PubMed1986

Diphosphonate intestinal activity seen on two bone images in neuroblastoma.

Neuroblastoma is well recognized as a cause of soft tissue uptake of Tc-99m MDP. Two cases of neuroblastoma arising in the midline from the celiac axis are reported. Bone imaging performed on two separate days showed not only typical soft tissue uptake, but also the appearance of the radiopharmaceutical in the bowel. At surgery, a midline upper abdominal neuroblastoma was found in both patients without evidence of involvement of the liver, kidneys, bowel, gallbladder or mesentery. It became apparent with delayed images in the second patient that this activity was in the bowel and moving around the abdomen in a typical large bowel pattern. Bowel activity was not seen in other patients having bone scans at this time. Follow-up bone imaging on the first patient after resection of the tumor did not demonstrate diphosphonate activity in the bowel. These authors have never seen or read of this finding previously in this condition, and report it in these two patients.

Abdominal Neoplasms↗
PubMed2001

Comparison of Tc-99m methylene diphosphonate, Tc-99m human immune globulin, and Tc-99m-labeled white blood cell scintigraphy in the diabetic foot.

PURPOSE: The aims of this prospective study were to evaluate the contribution of Tc-99m methylene diphosphonate (MDP), Tc-99m human immune globulin (HIG), and Tc-99m white blood cell (WBC) to the diagnosis of osteomyelitis in the diabetic foot and to evaluate the surgical or medical therapy with Tc-99m HIG and Tc-99m WBC scans. METHODS: Twenty patients (15 men, 5 women) with suspected pedal osteomyelitis were included in the study. All patients had type II diabetics. Three- and four-phase bone scintigraphy (3P-MDP, 4P-MDP), early (e) and late (l) HIG, and WBC scans were completed within 1 week in all patients. The lesion-to-background ratios were calculated for early and late images of the feet for all scans and named as the indices. Eight weeks after the end of medical or surgical therapy, Tc-99m HIG and Tc-99m WBC scans were repeated in 10 patients. The difference in indices between 3P-MDP and 4P-MDP for osteomyelitis and indices for osteomyelitis, cellulitis, and inflammation in Tc-99m HIG and Tc-99m WBC in early and late scans were tested for significance. RESULTS: In 20 patients, 53 lesions were investigated. Among these 53 lesions were 25 sites of proved osteomyelitis, 6 sites of cellulitis, and 22 sites of inflammation confirmed by radiography, microbiologic culture, and clinical evaluation. 4P-MDP was more specific than 3P-MDP for detecting osteomyelitis (50% and 67%, respectively). There was also a significant difference between the mean indices of 3P-MDP and 4P-MDP (P < 0.000). The index values were increased in 4P-MDP scans. There was no significant difference between the indices of early and late Tc-99m HIG scans for inflammation, cellulitis, and osteomyelitis. Early and late Tc-99m WBC scans did not show a significant difference in differentiating osteomyelitis. However, Tc-99m WBC scans could differentiate aseptic inflammation from infection (P < 0.031) in early and late scans. There was a significant difference of index values between pre- and post-treatment Tc-99m HIG and Tc-99m WBC scans. The best combination of scans for detecting osteomyelitis was 4P-MDP with WBC scans, with an accuracy rate of 92%. CONCLUSIONS: These results show that four-phase bone scintigraphy with early Tc-99m WBC scanning is preferred for detecting osteomyelitis of the diabetic foot. To evaluate the response to therapy, Tc-99m WBC scans are the preferred method, but if this is not available, Tc-99m HIG scanning can be used.

Adult↗
PubMed1992

The response of 99Tcm-methylene diphosphonate and 99Tcm-hexametazime-labelled neutrophils to intra-articular steroid injection in rheumatoid arthritis.

The synovial and bone uptake of tracer in the knees of patients with rheumatoid arthritis (RA) was quantified using 99Tcm-hexamethyl propylene amine oxime-labelled leucocytes and 99Tcm-methylene diphosphonate (MDP), respectively. Significant neutrophil migration and MDP uptake occurred in the knees of patients with RA irrespective of the disease duration. In all but one patient neutrophil migration was reduced after intra-articular steroid injection. The change in MDP uptake after steroid injection was variable. There was a significant correlation between the percentage reduction in neutrophil migration and pain score, while the latter correlated poorly with the change in MDP uptake. The quantification of the neutrophil component of the inflammatory process is a sensitive index for monitoring RA activity and response to pharmacological interventions, while quantitative bone scintigraphy should not be employed to monitor changes in joint inflammation in patients with RA.

Aged↗
PubMed1997

Radiation dose estimates of 186Re-hydroxyethylidene diphosphonate for palliation of metastatic osseous lesions: an animal model study.

A common complication in patients with breast or prostate cancer is bone metastases causing pain. New radionuclide therapy methods have recently been proposed for palliation, including 186Re-hydroxyethylidene diphosphonate (186Re-HEDP). This paper reports on the local development of 186Re-HEDP and the biodistribution studied in animals for eventual use in patients. Adult dose was computed assuming a 70 kg standard man. The 186Re was labelled to HEDP using standard techniques. The biodistribution in five Chacma baboons (Papio ursinus) was studied. Doses ranging from 39.4 to 44.9 MBq kg(-1) (mean 43.6 +/- 2.8 MBq kg[-1]) were administered, corresponding to an adult human dose of 2960 MBq (80 mCi). Whole-body images of the animals were obtained with a dual-headed scintillation camera on an hourly basis for 6 h post-injection and then daily for 3 days. The bone, soft tissue, kidneys and urinary bladder were considered source organs and data from these organs were used in a compartmental model to obtain the mean residence times of the radionuclide in the different source organs. Radiation dose estimates for 186Re-HEDP were subsequently obtained with the MIRDOSE 3 program. The estimated absorbed radiation doses to some of the organs (expressed in mGy MBq[-l]) were as follows: bone surface 1.69; kidneys 0.09; liver 0.04; ovaries 0.04; red marrow 0.75; total body 0.12; urinary bladder wall 0.43. 186Re-HEDP yielded an effective dose of 0.17 mSv MBq(-1). The radiation dose delivered to the bone marrow in this study did not cause any detrimental effect to the baboons, indicating that locally produced 186Re-HEDP is suitable for clinical use.

Adult↗
PubMed2001

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.

Aged↗
PubMed2003

Incremental diagnostic value of 99mTc methylene diphosphonate bone SPECT in patients with patellofemoral pain disorders.

Painful disorders of the patellofemoral joint are one of the most frequent complaints in orthopaedic and sports medicine. The purpose of this study was to assess the value of single photon emission computed tomography (SPECT) bone imaging compared with arthroscopy in the differential diagnosis of anterior knee pain. Twenty-seven patients with chronic anterior knee pain and 27 age matched control patients were examined prospectively. All patients underwent a detailed clinical history and a thorough physical examination of the knee. Planar and SPECT knee scintigraphy was performed using 99mTc methylene diphosphonate (99mTc-MDP). Subsequently, arthroscopic examination of all three compartments of the affected knee was performed. The association between the scintigraphic findings and arthroscopy was examined statistically. Planar and SPECT scintigrams were classified as follows: focal or diffuse uptake in the patella only (eight patients), uptake in the patella and a corresponding focus in the distal femur (12 patients), and uptake in the patella associated with linear increased activity along the distal femur (six patients). One patient had no patellofemoral SPECT abnormalities. Six of eight patients with isolated increased patellar activity were diagnosed with chondromalacia of the patella, while 2/8 patients had arthroscopic findings unrelated to patellofemoral abnormalities. Seven of 12 patients with corresponding uptake in the patella and distal femur were diagnosed with patellofemoral arthritis. Eleven other patients with corresponding patellar and femoral activity were diagnosed with increased lateral patellar compression syndrome. In these patients the patellar foci were always lateral, and they separated during flexion of the knee. Seven patients had further scintigraphic findings in addition to patellofemoral abnormalities, unsuspected clinically. Nine of 27 patients in the control group (33%) had either focal or diffuse increased patellar uptake. Compared to arthroscopy SPECT imaging had a sensitivity of 100% for patellofemoral abnormalities and a specificity of 64% (negative predictive value, 100%; and positive predictive value, 72%). The overall observed agreement between SPECT and arthroscopy was 81% (kappa=0.63). It is concluded that SPECT imaging of the knee is highly sensitive for the diagnosis of patellofemoral abnormalities. SPECT significantly improves the detection of maltracking of the patella and the ensuing increased lateral patellar compression syndrome. This information could be used to treat patellofemoral problems more effectively.

Adult↗
PubMed2003

A direct in vivo measurement of 99mTc-methylene diphosphonate protein binding.

Quantitative studies of the kinetics of 99mTc-methylene diphosphonate (99mTc-MDP) in metabolic and metastatic bone disease require the measurement of free tracer in plasma to derive the input function. We describe a simple method of determination of free 99mTc-MDP in vivo based on measurements of the ratio of the renal plasma clearances of total 99mTc-MDP and 51Cr-ethylenediaminetetraacetic acid (51Cr-EDTA). The method is based on evidence that free MDP is cleared through the kidneys by glomerular filtration. Measurements of the fraction of free 99mTc-MDP were made between 0 and 4 h after injection in 70 postmenopausal women enrolled in a study of the effect of hormone replacement therapy on the whole-skeleton plasma clearance of 99mTc-MDP (K(bone)). The glomerular filtration rate (GFR) was measured simultaneously from the plasma clearance of 51Cr-EDTA. The mean fractions (and SD) of free MDP measured were 0.757 (0.050), 0.663 (0.062), 0.550 (0.052) and 0.472 (0.053), respectively, at 17, 90, 150 and 210 min after injection. The results agreed closely with data using protein precipitation with trichloroacetic acid. Between 2 and 4 h after injection, the biological half-life of free 99mTc-MDP in plasma was 92 min, compared with 540 min for bound MDP. Highly significant relationships were found between the fraction of free MDP measured in each patient at each of the four time points and the total plasma clearance of free 99mTc-MDP (K(total)=GFR+K(bone)), such that a larger value of K(total) was associated with a smaller fraction of free MDP. Multivariate regression analysis confirmed that this relationship held individually for both GFR and K(bone). A strong inverse relationship was found between K(total) and the plasma concentration of free 99mTc-MDP, but a much weaker relationship with the bound MDP concentration, a finding that is consistent with the slow re-equilibration of bound MDP in the circulation. The results confirm that the fraction of free 99mTc-MDP varies with time and shows significant differences between individuals, which are dependent on GFR and K(bone) amongst other factors.

Aged↗
PubMed2006

A report on the incidence of intestinal 99mTc-methylene diphosphonate uptake of bone scans and a review of the literature.

BACKGROUND: In addition to well-known specific conditions for soft-tissue uptake of bone-seeking radiotracers, there is a limited number of reports on intestinal uptake of (99m)Tc-methylene diphosphonate ((99m)Tc-MDP) on bone scans. AIM: To describe the incidence of intestinal accumulation of (99m)Tc-MDP on bone scans in adult patients, define the patterns of this unusual finding and review the literature on its causes. METHODS: Two thousand, one hundred and forty-four consecutive patients have been evaluated for intestinal (99m)Tc-MDP uptake on bone scans. Intestinal uptake was observed visually 3-4 h after the administration of the radiopharmaceutical. A whole-body bone scan and various spot views of the abdomino-pelvic region were obtained with a dual-headed gamma camera to evaluate the intestinal uptake. Delayed scans were also obtained as well as co-relative imaging and/or colonoscopic studies in some of intestinal uptake patients. Six patients had delayed scans of the abdomino-pelvic region. Fourteen patients had comparable scans either a year before or a year later. The positive intestinal uptake scans were further grouped according to the localization and intensity (mild uptake: lower than iliac bone; moderate uptake: equal to iliac bone; significant uptake: higher than iliac bone). RESULTS: Twenty-two (17 female, five male) patients out of 2144 with a mean age of 57 years showed intestinal (99m)Tc-MDP uptake. The localization was mainly (20/22) in the right abdomino-pelvic region projecting on and in the configuration of ascending colon while one patient showed intestinal uptake all over the abdomen and one displayed diffuse intestinal radioactivity in his right hemithorax. The majority of the cases showed moderate to intense intestinal uptake (18/22). Six patients showed a decrease, disappearance or alteration in the intestinal uptake on the delayed images. Re-evaluation bone scans in five patients 1 year later showed no intestinal uptake this time. Among nine patients with prior bone scans 1 year before, intestinal uptake was negative in seven at that time. No significant pathology was obtained on the correlative images. CONCLUSION: (99m)Tc-MDP uptake can be observed in the intestines in 1% of bone scans with a prominent localization in the ascending colon and rarely all over the intestines or in thorax due to Chilaiditi's syndrome, as well. The mechanism of intestinal uptake is still unclear in some of the patients. Delayed imaging, additional spot views and SPECT studies help in the differentiation of this finding from possible misinterpretation. Intestinal (99m)Tc-MDP uptake on bone scan could be an intermittent process and should be included among other well-known reasons of soft-tissue uptake.

Body Burden↗
PubMed2006

Clinical value of planar and tomographic dual-isotope scintigraphy using 99mTc-methylene diphosphonate and 131I in patients with thyroid cancer.

PURPOSE: (131)I whole-body scintigraphy is a highly sensitive method for the detection of differentiated thyroid tumours and metastases. However, a lack of anatomical landmarks and the physiological excretion of the tracer complicates the evaluation of the images. Therefore, we determined whether additional bone scintigraphy in combination with (131)I scintigraphy, simultaneously acquired via planar and tomographic techniques, positively contributes to the treatment plan in patients with non-conclusive (131)I images. METHODS: Twenty-one patients with differentiated thyroid cancer and known metastases or unclear findings in the (131)I whole-body scan underwent dual-isotope scintigraphy (DIS) within 2-7 days after application of 5000-8000 MBq (131)I. Dual-energy planar and tomographic data were acquired simultaneously and the results compared with other imaging modalities. RESULTS: In 48% of the cases (10 of 21), DIS supplied important additional information that either altered the treatment plan or staging of the patients. In 28% (six of 21), DIS provided new information that was not known before, but did not change the staging of the patients. In five cases (24%), DIS did not add any new data regarding the extent of the disease. CONCLUSIONS: The simultaneous acquisition of (131)I and (99m)Tc-methylene diphosphonate provides clear landmarks and facilitates the localization of functioning metastases from differentiated thyroid cancer as well as improves the fusion with morphological images. It can be performed easily and also transferred to other isotope combinations.

Adult↗
PubMed2005

Technetium-99m diphosphonate imaging of psammocarcinoma of probable ovarian origin: case report and literature review.

Technetium-99m methylene diphosphonate (Tc-99m MDP) bone scans have long been used by clinicians to diagnose osseous metastases in patients with cancer. However, in several benign and malignant diseases, notably those characterized by extensive soft tissue calcification, Tc-99m MDP may be taken up by the tumor itself. We present a case of a stage IIIC psammoma-rich low-grade serous carcinoma of the ovary, whose identity and extent of disease were first suggested by Tc-99m MDP scintigraphy. The literature concerning this form of cancer, and the use of Tc-99m MDP bone scans to image soft tissue lesions, are reviewed.

Cystadenocarcinoma, Serous↗
PubMed1986

Effects of disodium ethane-1-hydroxy-1,1-diphosphonate (EHDP) on interleukin 1 production by macrophages.

The effects of disodium ethane-1-hydroxy-1,1-diphosphonate (EHDP) on the in vitro functions of guinea pig macrophages were studied. A high dose (1 mg/ml) of EHDP inhibited interleukin 1 (IL 1) production by oil-induced peritoneal macrophages stimulated with muramyl dipeptide (MDP), lipopolysaccharide (LPS), phorbol myristic acetate (PMA), heat-aggregated IgG2 or calcium ionophore A23187. On the other hand, low doses (less than 0.125 mg/ml) of EHDP augmented the MDP induced IL 1 production by macrophages. This biphasic effect was also observed when macrophages were exposed to EHDP at 37 C for 24 hr and then stimulated with IL 1 inducers. Superoxide anion generation induced by formyl peptide or PMA was not affected by preincubation of the macrophages with doses of EHDP up to 1 mg/ml. Adherence and spreading of macrophages was inhibited by EHDP in a dose dependent manner without affecting cell viability. These results demonstrated that EHDP acted on macrophages directly and modulated IL 1 production in vitro.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1986

Absorption of oral diphosphonate in normal subjects.

Absorption of the diphosphonate etidronate (HEDP) was measured in 20 volunteer subjects at two centres (Glasgow and Madison) using a new method based on simultaneous administration of HEDP and intravenous 99mTc-HEDP (Osteoscan). The mean absorption of HEDP in fasting subjects in Glasgow was 3.5% (range 1-8.9%) and in Madison 1.5% (0.7-2.8%) (P less than 0.035). In four subjects studies were repeated with good agreement between results (mean 3.9 cf. 3.5%). Six subjects had studies repeated when drug was ingested with food and in all cases absorption was effectively reduced to zero. We conclude that absorption of HEDP is significantly higher in normal subjects in Glasgow than in Madison. This may be of importance with regard to the finding of histological osteomalacia and fracture associated with HEDP use in Glasgow.

Administration, Oral↗
PubMed1976

Diphosphonate therapy in nephrocalcinosis.

4 patients with nephrocalcinosis were treated with disodium ethane 1-hydroxy-1, 1-diphosphonate (EHDP) for a period of 13 months. No clinical side-effects were observed and growth proceeded normally. Radiographic changes of osteitis fibrosa cystica developed in 1 child and bone biopsy in 2 children showed defective osteoid mineralisation. It is suggested that EHDP prevented further crystal deposition in 3 children but did not prevent non-calcium stone formation in the 4th child. In view of this and the development of histological and radiographic evidence of osteomalacia and/or secondary hyperparathyroidism in these patients the value of EHDP remains dubious. On the other hand its use may be justified when rapidly increasing calcification is expected, as for example in hyperoxaluria.

Bartter Syndrome↗