Value of antigranulocyte scintigraphy with Tc-99m-sulesomab in diagnosing combat-related infections of the musculoskeletal system.

AIM: Combat-related extremity injuries are regularly associated with long-term complications such as chronic infection, especially osteomyelitis. Clinical examination and laboratory parameters do not usually allow reliable diagnosis. In contrast, imaging techniques enable constructive assertions to be made about the location and extent of an infection of the peripheral musculoskeletal system. The aim of this study was therefore to determine the diagnostic reliability of three-phase bone scanning and antigranulocyte scintigraphy using Tc-99m-sulesomab (Leukoscan) in the diagnostic clarification of infections associated with combat-related extremity injuries. METHODS: Twenty-seven male patients (mean age 33.9 years) with suspected combat-associated infections of the extremities were included in this retrospective analysis. All patients underwent three-phase bone scanning using Tc-99m-HDP followed by antigranulocyte scintigraphy with Tc-99m-sulesomab. In 26 of the 27 patients, a CT scan of affected limb was obtained, where the secondary fusion with single photon emission CT data set was possible. The diagnostic reliability of imaging techniques was validated against microbiological samples obtained during surgery and used as gold standard. RESULTS: Three-phase bone scanning yielded a positive result in all patients, with 18 scans classified as true positive (TP) and nine scans as false positive (FP). This produced a sensitivity of 100%, a specificity of 0% and a positive predictive value (PPV) of 67%. Antigranulocyte scintigraphy recognised 13 patients as TP, 1 patient as FP, 8 patients as true negative (TN) and 5 patients as false negative (FN), which gave a sensitivity of 72%, a specificity of 88%, a PPV of 93%, a negative predictive value (NPV) of 62% and an accuracy of 78%. CT recognised in 7 cases a TP result, in 3 cases an FP, in 5 cases a TN and in 11 cases an FN result. This produced a sensitivity of 39%, a specificity of 63%, a PPV of 70%, an NPV of 31% and an accuracy of 46%. CONCLUSIONS: Three-phase bone scanning did not deliver any diagnostic benefit, since no result was able to differentiate unequivocally between infection-related and reactive changes. Antigranulocyte scintigraphy using Tc-99m-sulesomab represented a highly suitable technique for diagnostically clarifying combat-related infections of the extremities. It is superior to CT in sensitivity, specificity, PPV, NPV and accuracy.

Is 99m Tc bone scintigraphy necessary in the preoperative workup for patients with cT1N0 subsolid lung cancer? A prospective multicenter cohort study.

BACKGROUND: 99m Tc bone scintigraphy (BS) is still the most common approach for the evaluation of bone metastasis in China. The purpose of this study was to investigate the necessity of BS as part of a routine preoperative workup for patients with cT1N0 subsolid lung cancer. METHODS: This was a prospective multicenter clinical trial (NCT03689439). Patients with cT1N0 subsolid nodules who were candidates for surgical resection were consecutively enrolled into the study. BS was performed preoperatively. The surgical plan could be changed if a positive result was detected. The primary endpoint was the incidence rate of the surgical plan being changed because of positive BS results. The secondary endpoint was the rate of positive BS findings and the rate of related complications. RESULTS: From November 2018 to July 2019, 691 patients were enrolled into the study. None of the patients had positive BS results and no surgical plans were changed by BS findings. There were 222 male and 469 female patients. The average age was 54.8 ± 3.7 years old. The average tumor diameter was 14.9 ± 4.2 mm. There were 282 patients with pure GGO nodules and 409 with part-solid nodules. A total of 470 patients had a single nodule, while 221 patients had multifocal lesions. The number of patients whose pathological diagnosis was invasive adenocarcinoma, minimally invasive adenocarcinoma, adenocarcinoma in situ and mucinous adenocarcinoma was 357, 293, 32 and nine, respectively. The number of patients who underwent lobectomy, segmentectomy and wedge resection was 234, 199 and 258, respectively. CONCLUSIONS: 99m Tc bone scintigraphy is unnecessary in the preoperative workup for patients with cT1N0 subsolid lung cancer. KEY POINTS: SIGNIFICANT FINDINGS OF THE STUDY: In this prospective study of 691 patients with cT1N0 subsolid lung cancer, no surgical plans were affected by positive bone scan findings. WHAT THIS STUDY ADDS: We suggest physicians consider canceling BS from preoperative workup for cT1 subsolid lung cancer patients. Clinical trial registry number: NCT03689439.

Effect of technetium-99 conjugated with methylene diphosphonate (99 Tc-MDP) on OPG/RANKL/RANK system in vitro.

BACKGROUND: RANKL and RANK play an important role in jaw resorption during the development of the ameloblastomas. Therefore, the aim of this study was to explore the effect of 99 Tc-MDP on OPG/RANKL/RANK system on RAW264.7 and MC3T3-E1 cell lines in vitro and provide the theoretical basis for the clinical treatment of the jaw ameloblastoma. METHODS: Different concentrations of 99 Tc-MDP were used to treat RAW264.7 and MC3T3-E1 cell lines. The cell proliferative inhibition rate was analyzed by CCK-8. Cell apoptosis and cell cycle were detected by flow cytometry. Western blot was used to detect the expression of OPG, RANKL, and RANK. RESULTS: Treatment of RAW264.7 cell lines with different concentrations of 99 Tc-MDP had inhibitory effects and decreased the expression of RANK protein. The cell proliferation of 99 Tc-MDP on MC3T3-E1 cell lines was stronger at 48 hours than at 24 hours except for 100 µg/mL concentration group. Compared with the concentration of 0.01 µg/mL, the treatment of MC3T3-E1 cells with 100 µg/mL 99 Tc-MDP showed that the cell proliferative effect decreased at 24 hours and 48 hours (P < 0.05). After treatment with 0.01 µg/mL 99 Tc-MDP, the expression of OPG in MC3T3-E1 cells was significantly increased (P < 0.05). Compared with 0.01 µg/mL, the expression of RANKL was decreased after treatment with 100 µg/mL 99 Tc-MDP (P < 0.05). CONCLUSION: 99 Tc-MDP can induce apoptosis of RAW264.7 cells and inhibit the expression of RANK protein. The effect of 0.01 µg/mL of low concentration of 99 Tc-MDP can promote the proliferation of MC3T3-E1 cells and increase the expression of OPG and RANKL protein. 99 Tc-MDP may have adjuvant therapeutic effects on the treatment of jaw ameloblastoma.

99Tc-MDP-induced human osteoblast proliferation, differentiation and expression of osteoprotegerin.

The aim of the present study was to examine the influence of technetium methylenediphosphonate (99Tc-MDP) on the proliferation and differentiation of human osteoblasts. Human iliac cancellous bone was isolated and cultured with either 99Tc­MDP, ß fibroblast growth factor (as a positive control) or medium only (as a negative control). Proliferation was assessed by direct cell counting, CCK­8 assay and bromodeoxyuridine staining. The cell cycle and rate of apoptosis was assessed by propidium iodide staining and flow cytometry. Alkaline phosphatase (ALP) activity was assessed by the p­nitrophenyl phosphate method and mineralized nodules were stained with Alizarin Red. Expression of osteocalcin (OCN) and bone morphogenetic protein­2 (BMP­2) was assessed by reverse transcription­quantitative polymerase chain reaction (RT­qPCR), and expression levels of osteoprotegerin (OPG) and receptor activator of NF­κB ligand (RANKL) were assessed by RT­qPCR and ELISA. Isolated human osteoblasts stained positively for ALP and developed mineralized nodules. Treatment with 10­5­10­10 M 99Tc­MDP enhanced proliferation and 48 h incubation with 10­8 M 99Tc­MDP increased the proportion of cells in S­phase, decreased the proportion in G0/G1 phase, and increased the cell proliferation index. The rate of apoptosis also increased, but the increase was not significant. Cells incubated with 10­6­10­9 M 99Tc­MDP for 3­9 days exhibited increased ALP activity and mineralized nodule development. 10­8 M 99Tc­MDP increased BMP­2 and OPG expression levels and OPG secretion, but OCN mRNA expression levels and RANKL secretion were not significantly altered at 72 h. 99Tc­MDP treatment induced osteoblast proliferation and differentiation without affecting apoptosis. These findings provide proof of concept for the future use of 99Tc­MDP in the treatment of bone­destructive diseases.

Benign incidental findings of osteopoikilosis on Tc-99m MDP bone SPECT/CT: A case report and literature review.

Osteopoikilosis is a benign but rare condition characterized by bone islands throughout the osseous tissue, which could be easily confused with bone metastasis. We present a case of a 37-year-old man presented to orthopedic outpatient clinic with right hip pain for 2 weeks. There were multiple, small punctate lesions scattered throughout the skeleton on radiograph. Subsequent Tc-99m methylene diphosphonate (MDP) bone scan with pelvic single-photon emission computed tomography (SPECT)/computed tomography (CT) showed multiple enostoses without abnormal focal MDP uptake. Therefore, clinical diagnosis was compatible with osteopoikilosis while bone metastasis was unlikely. The symptoms then improved by conservative treatments. Osteopoikilosis is usually an incidental finding on radiograph or CT, and a normal MDP confirmed the diagnosis by excluding bone metastasis. It is important for clinicians to recognize the specific image features to prevent further unnecessary interventions. In addition, bone SPECT/CT could also make the diagnosis in one step.

Technetium-99 conjugated with methylene diphosphonate inhibits receptor activator of nuclear factor-κB ligand-induced osteoclastogenesis.

1. In the present study, we investigated the effects of technetium-99 conjugated with methylene diphosphonate ((99)Tc-MDP), an agent used in radionuclide therapy, on receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis and explored the underlying mechanisms. 2. The murine macrophage cell line RAW264.7 and bone marrow-derived-macrophages from C57BL/6 mice (BMM) were used as models for osteoclastogenesis in vitro. The expression of some key factors in RANKL (50 ng/mL)-induced osteoclastogenesis in RAW264.7 cells was investigated by flow cytometry and real-time reverse transcription-polymerase chain reaction (RT-PCR). To detect multinucleated osteoclast formation, RAW264.7 cells were induced with RANKL for 4 days, whereas BMM were induced by 50 ng/mL RANKL and 20 ng/mL macrophage colony-stimulating factor for 7 days, before being stained with tartrate-resistant acid phosphatase. 3. Osteoclastogenesis was evaluated using the osteoclast markers CD51, matrix metalloproteinase (MMP)-9 and cathepsin K. At 0.01 µg/mL, (99)Tc-MDP significantly inhibited RANKL-induced osteoclastogenesis without any cytotoxicity. In addition, (99)Tc-MDP abolished the appearance of multinucleated osteoclasts. 4. Real-time RT-PCR analysis of transcription factor expression revealed that (99)Tc-MDP inhibited the expression of c-Fos and nuclear factor of activated T cells. In addition, (99)Tc-MDP inhibited the expression of the inflammatory factors interleukin (IL)-6, tumour necrosis factor-α and IL-1ß. Finally, (99)Tc-MDP inhibited the activation of mitogen-activated protein kinases in RAW264.7 cells following RANKL stimulation. 5. In conclusion, (99)Tc-MDP possesses anti-osteoclastogenic activity against RANKL-induced osteoclast formation.

Technetium-99 conjugated with methylene diphosphonate (99Tc-MDP) inhibits experimental choroidal neovascularization in vivo and VEGF-induced cell migration and tube formation in vitro.

PURPOSE: To investigate the effects of (99)Tc-MDP, a decay product of (99m)Tc-MDP, on the development of choroidal neovascularization (CNV), together with its underlying mechanisms. METHODS: C57BL/6J mice were used to induce CNV by laser photocoagulation. (99)Tc-MDP at the doses of 0.5 × 10(-1), 1 × 10(-1), and 2 × 10(-1) µg/kg or the same volume of PBS was intraperitoneally injected daily after photocoagulation until the end of the experiment. Seven days after laser injury, mice were perfused with fluorescein-labeled dextran, and areas of CNV were measured. Numbers of infiltrating macrophages, protein levels of VEGF, and inflammation-related molecules including intercellular adhesion molecule (ICAM)-1, tumor necrosis factor (TNF)-α, and matrix metalloproteinases (MMPs) in the RPE-choroid complex were detected 3 days after laser photocoagulation. Effects of (99)Tc-MDP on VEGF-induced endothelial cell migration and tube formation were also studied. Toxicity of (99)Tc-MDP was evaluated in vivo and in vitro. RESULTS: Areas of CNV were significantly suppressed by (99)Tc-MDP treatment without toxicity to the retina compared with PBS treatment in a dose-dependent manner: (99)Tc-MDP treatment of 0.5 × 10(-1) µg/kg (5698.60 ± 1037.70 µm(2)), 1 × 10(-1) µg/kg (3678.34 ± 1328.18 µm(2)), and 2 × 10(-1) µg/kg (2365.78 ± 923.80 µm(2)) suppressed the development of CNV by 36.12%, 58.76%, and 73.48%, respectively, compared with that in the PBS treatment group (8920.36 ± 1097.29 µm(2); P < 0.001). (99)Tc-MDP treatment led to significant inhibition of macrophages infiltrating to CNV together with downregulated protein expressions of VEGF, ICAM-1, TNF-α, and MMP-2. (99)Tc-MDP also showed an inhibitive effect on cell proliferation and VEGF-induced migration and capillary-like tube formation of endothelial cells. CONCLUSIONS: Anti-inflammatory treatment with (99)Tc-MDP has therapeutic potential for CNV-related diseases.

Effects of technetium-99 methylenediphosphonate on cytokine-induced activation of retro-ocular fibroblasts from patients with Graves' ophthalmopathy.

OBJECTIVE: To explore the effects of technetium-99 methylenediphosphonate (99Tc-MDP) on cell proliferation, hyaluronic acid (HA) synthesis and the expressions of human leucocyte antigen-DR (HLA-DR), intercellular adhesion molecule-1 (ICAM-1) on cultured retro-ocular fibroblasts (RFs) from patients with Graves' ophthalmopathy. METHODS: After two to seven passages, cultured RFs were incubated for 72 h with interferon-γ (100 U/ml), interleukin-1 (100 U/ml) or tumour necrosis factor-α (100 U/ml) in the presence of 99Tc-MDP. Flow cytometry was used to investigate the expression of HLA-DR and ICAM-1. RF proliferation was assessed by 3H-thymidine incorporation assay. HA synthesis was measured by radioimmunoassay. RESULTS: At base conditions, the percentage of positive cells of HLA-DR and ICAM-1 on RFs was 6.70±3.06% and 5.29±3.02%, respectively, and the synthesis of HA was 337.8±42.7 ng/ml. Compared with basal values, 72-h incubation with cytokine significantly enhanced the expression of HLA-DR and ICAM-1, and HA synthesis. 99Tc-MDP (1 ng/ml) had little effect on cytokine-induced HLA-DR and ICAM-1 expression, and HA synthesis. When the concentration ranged from 10 to 100 ng/ml, 99Tc-MDP inhibited cytokine-induced RF activation in a dose-dependent manner. 99Tc-MDP also inhibited the proliferation of RFs in a dose-dependent manner. It was also found that 99Tc-MDP had the same effect on cytokine-induced RFs and skin fibroblasts from patients with normal individual conditions. CONCLUSIONS: 99Tc-MDP could inhibit cytokine-induced activation of RFs derived from patients with Graves' ophthalmopathy.

Effects of 99mTc-MIBI and 99mTc-MDP administration on dual-energy X-ray absorptiometry bone mineral density measurements.

OBJECTIVE: Nuclear medicine procedures are often performed in close-time proximity to bone densitometry studies. The purpose of this study was to determine the effects of Tc-hexakis-2-methoxyisobutyl isonitrile (MIBI) and Tc-methylene diphosphonate (MDP) on the accuracy of bone mineral density (BMD) measurements performed using dual-energy X-ray density. METHODS: The effect of a diagnostic dose of Tc-MIBI on BMD estimations in the lumbar spine and the left total hip was assessed in 30 patients (19 female, 11 male; mean age: 55.5+/-10.5 years) by using a Lunar DPX-NT scanner. Thirty patients, admitted to the nuclear medicine department for bone scintigraphy (15 female, 15 male; mean age: 56+/-15.92 years), were included into the study. Each patient underwent dual-energy X-ray density assessment for which a Lunar DPX-NT scanner was used before and 2 h after intravenous injection of Tc-MDP (925 MBq) and Tc-MIBI (1110 MBq). BMD measurements were calculated from lumbar spine (including L2-4) and left hip (including femoral neck, trochanter, and total hip). For statistical analysis, the Wilcoxon test was used and a P value of less than 0.05 was accepted as statistically significant. RESULTS: According to Wilcoxon's statistical test, we found extremely significant changes on the measured BMD, T-score, before and 2 h after the injection of Tc-MIBI for lumbar spine and left hip in 30 patients. We found statistically significant decrement on measured BMD from lumbar spine and trochanter before and 2 h after the injection of Tc-MDP. Although MDP BMD values in femoral neck and total hip were decreased after the injection of Tc-99m, they did not reach a statistically significant value. The comparison of pre-T-score and post-T-score values showed a statistically significant decrease after the injection for only L2-4 lumbar spine (P = 0.002), but left hip of pre-T-score and post-T-score values did not reach a statistically significant value. CONCLUSION: In this study, it was determined that measured BMD values are decreased in lumbar spine for all patients. The magnitude of the effect is dependent on the location of the activity. We assume that some radioactivity from Tc is counted by the densitometer's detector, thus resulting in a decrease in the measured BMD. Scintigraphy and bone densitometry should be performed on different days to avoid artifactual reduction in BMD measurements.

Bone scan findings in metastatic calcification from calciphylaxis.

A 51-year-old woman on peritoneal dialysis for chronic renal failure secondary to diabetic and nonsteroidal anti-inflammatory drug nephropathy was referred for a Tc-99m MDP bone scan to assess firm subcutaneous plaques in the sacral and gluteal regions. This showed extensive superficial tracer localization in the subcutaneous tissues as well as visceral tracer activity in the myocardium, lungs, stomach, and kidneys. These findings were typical for calciphylaxis (calcific uremic arteriolopathy), a form of metastatic calcification encountered in patients with chronic renal failure that is characterized by subcutaneous soft tissue calcification, painful ulcerations, high morbidity, and mortality. Treatment with sodium thiosulfate resulted in dramatic scintigraphic improvement.

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.

Chronic recurrent multifocal osteomyelitis (CRMO) with symmetric involvement of both femora: X-ray, bone scintigram, and MR imaging findings in one case.

The case of a 17-month-old boy with symmetric involvement of both femora in chronic recurrent multifocal osteomyelitis (CRMO) is presented. Imaging showed an extraordinary involvement of both femoral diaphyses and distal metaphyses with extensive lamellar-like periosteal reactions. Diagnosis was based upon laboratory tests, bone scintigraphy, and MRI findings and was proved by open bone biopsy.

The role of radioisotopic methods in imaging of intervertebral disc inflammation in children.

The authors present the case of a 17-year-old girl, with pain over lumbar spine area, treated by paediatricians and rehabilitation specialists, discussing diagnostic imaging and laboratory examinations together with clinical observations. Spondylodiscitis was diagnosed after bone scintigraphy with 99mTc-MDP, the course of disease was monitored by immunoscintigraphy amongst other techniques.

Antecedent 99mTc-MDP and 99mTc-sestamibi administration corrupts bone mineral density measured by DXA.

Previous reports of the effect of antecedent administration of radionuclide on bone mineral density (BMD) measurements have yielded inconsistent results. Ten subjects scheduled for (99m)Tc-methylene diphosphonate ((99m)Tc-MDP) bone scanning and 10 scheduled for (99m)Tc-sestamibi cardiac scanning had BMD measured by dual X-ray absorptiometry (DXA) (GE/Lunar) before and within 5 hours of diagnostic radionuclide injection. Paired t test and Wilcoxon-signed rank tests were used to compare the measured differences in BMD at multiple skeletal sites. Differences were subjected to multivariate analysis of demographic factors. Mean change in measured BMD following (99m)Tc-sestamibi administration (DeltaBMD-(99m)Tc-sestamibi) was -0.216+/-0.113 g/cm(2) at the total body and -0.348+/-0.300 g/cm(2) at the lumbar spine (p<0.005). Mean change in measured BMD following (99m)Tc-MDP administration (DeltaBMD-(99m)Tc-MDP) was -0.058+/-0.037 g/cm(2) at the total body and -0.053+/-0.049 g/cm(2) at the lumbar spine (p<0.05). Mean DeltaBMD-(99m)Tc-sestamibi exceeded least significant change (LSC) in all skeletal sites except the femoral trochanter. Mean DeltaBMD-(99m)Tc-MDP exceeded LSC only at the lumbar spine. The effect was correlated with (99m)Tc dose but not with gender, age, body mass index, baseline BMD, or time interval from injection to scan acquisition. In conclusion, BMD measured by the GE/Lunar Prodigy densitometer is corrupted by antecedent (99m)Tc-sestamibi and to a lesser extent by (99m)Tc-MDP. This effect is greater at the total body and lumbar spine than at the hip. Caution is warranted in scheduling and interpreting DXA studies when (99m)Tc has been recently administered.

Reversible metastatic visceral calcification detected by 99mTc-methylene diphosphonate bone scanning in breast cancer.

Diffuse metastatic visceral calcification is rare in breast cancer. We report on a 57-year-old woman with breast cancer and hypercalcemia who had diffuse metastatic visceral calcifications on lungs, myocardium, stomach, and thyroid on a (99m)Tc-methylene diphosphonate bone scan. Visceral calcifications were completely resolved 6 months after successful anticancer and zoledronic acid treatments. Bone scanning offers a useful diagnostic tool for both identifying visceral calcification and assessing the response to therapy in chemosensitive malignities with hypercalcemia such as breast cancer.

The potential use of 99mTc-MDP bone scans to plan high-activity 186Re-HEDP targeted therapy of bony metastases from prostate cancer.

Patients with skeletal metastases from hormone-refractory prostate cancer have shown variable responses to high-activity therapy with (186)Re-HEDP and peripheral stem cell support. In this paper, we report on the use of a novel technique to compare sequential planar images acquired post-(186)Re-HEDP therapy administration with pretherapy diagnostic (99m)Tc-MDP scans, to evaluate the turnover of the radiopharmaceutical in normal and abnormal bone. It was found that the activity in normal (i.e., disease-free) segments of the spine demonstrates a faster effective decay than that of the metastases, with the latter showing only physical decay. This study showed, for the first time, a detailed correlation in the behavior of the (99m)Tc-MDP and (186)Re-HEDP images, encouraging the possibility of using the pretherapy 99mTc-MDP scan for estimations of absorbed doses to be delivered by prescribed activities of (186)Re-HEDP.

Effect of 99mTc-MDP administration on dual-energy X-ray absorptiometry bone mineral density measurements.

The effect of a diagnostic dose of (99m)Tc-MDP on bone mineral density (BMD) estimations in the lumbar spine and the neck of femur was assessed in 20 patients using a Hologic QDR4500 scanner. Each patient underwent a DXA assessment prior to and 1 h following injection of (99m)Tc-MDP (mean dose-910 MBq). For comparative purposes, the precision of BMD estimation without the presence of a radioisotope was assessed by performing two sequential DXA studies on 30 volunteers and was found to be less than 0.01 g/cm(2). No significant change in BMD reading was detected following (99m)Tc-MDP injection for either measurement site and the precision of the readings was similar to that observed for the 30 volunteers. This study has shown that any effect produced by a typical bone scan dose of (99m)Tc-MDP is small in comparison with the intrasubject variance when estimating BMD using a Hologic QDR4500 scanner.

Preclinical investigations of drug and radionuclide conjugates of bisphosphonates for the treatment of metastatic bone cancer.

The potential targeting of therapeutic bisphosphonate conjugates to bone metastatic lesions was evaluated in vivo in mice. A bisphosphonate conjugate with 5-fluorouracil was synthesized as a potential chemotherapy agent, and a bisphosphonate conjugate with diethylenetriaminepentaacetic acid (DTPA) was prepared as a potential carrier of cytotoxic radionuclides. The compounds are hypothesized to be able to deliver either high doses of radiation or a high concentration of chemotherapy agents at sites of increased osteoclastic activity in patients with bony metastases while exhibiting minimal toxicity to normal tissues. Tissue distribution studies with the 99mTc-labeled bisphosphonate conjugates with DTPA and 5-fluorouracil showed rapid blood clearance and excretion of unbound activity, clearance from most tissues, and substantial retention of the bisphosphonates in bone. For the DTPA conjugate, activity in the bone represents 13.6% of the total injected dose at 8 hours following injection, representing 54.3% of the total whole-body activity at this time period. Under the same conditions, the 5-fluorouracil conjugate showed a 17.1% bone uptake at 60.2% of the whole-body activity. This normal bone uptake predicts that high concentrations of conjugates are expected to be achieved at sites of bone metastatic disease. Chemotherapy and radiotherapy studies with these compounds in animal models of metastatic bone cancer are underway.