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.

SAPHO Syndrome Involving the Mandible Treated With 99Tc-MDP.

SAPHO (synovitis-acne-pustulosis-hyperostosis-osteitis) syndrome is a chronic inflammatory disease involving multiple organs such as skin and bones. At present, its etiology and pathogenesis are still unclear. Due to the variety of clinical manifestations and the small number of SAPHO syndrome involving the mandible, accurate diagnosis is difficult for oral and maxillofacial surgeons. Here, the authors report that a male patient with SAPHO syndrome involving the maxillofacial skin and mandible, followed for 3 years. We used Tc-MDP (technetium-99 conjugated with methylene disphosphonate) (commercially known as Yunke) to treat this disease and achieved significant clinical treatment. This suggests that Tc-MDP can be used as a bisphosphonate to treat SAPHO syndrome.

18 F-NaF PET/CT IMAGING IN FIBROUS DYSPLASIA OF BONE.

Fibrous dysplasia (FD) is a mosaic skeletal disorder resulting in fractures, deformity, and functional impairment. Clinical evaluation has been limited by a lack of surrogate endpoints capable of quantitating disease activity. The purpose of this study was to investigate the utility of 18 F-NaF PET/CT imaging in quantifying disease activity in patients with FD. Fifteen consecutively evaluated subjects underwent whole-body 18 F-NaF PET/CT scans, and FD burden was assessed by quantifying FD-related 18 F-NaF activity. 18 F-NaF PET/CT parameters obtained included (i) SUVmax (standardized uptake value [SUV] of the FD lesion with the highest uptake); (ii) SUVmean (average SUV of all 18 F-NaF-positive FD lesions); (iii) total volume of all 18 F-NaF-positive FD lesions (TV); and (iv) total FD lesion activity determined as the product of TV multiplied by SUVmean (TA = TV × SUVmean ) (TA). Skeletal outcomes, functional outcomes, and bone turnover markers were correlated with 18 F-NaF PET/CT parameters. TV and TA of extracranial FD lesions correlated strongly with skeletal outcomes including fractures and surgeries (p values ≤ 0.003). Subjects with impaired ambulation and scoliosis had significantly higher TV and TA values (P < 0.05), obtained from extracranial and spinal lesions, respectively. Craniofacial surgeries correlated with TV and TA of skull FD lesions (P < 0.001). Bone turnover markers, including alkaline phosphatase, N-telopeptides, and osteocalcin, were strongly correlated with TV and TA (P < 0.05) extracted from FD lesions in the entire skeleton. No associations were identified with SUVmax or SUVmean . Bone pain and age did not correlate with 18 F-NaF PET/CT parameters. FD burden evaluated by 18 F-NaF-PET/CT facilitates accurate assessment of FD activity, and correlates quantitatively with clinically-relevant skeletal outcomes. © 2019 American Society for Bone and Mineral Research.

Comparison of Ga-68 PSMA positron emission tomography/computerized tomography with Tc-99m MDP bone scan in prostate cancer patients

Background/aim: The aim of our study was to compare Tc-99m MDP bone scan and Ga-68 PSMA PET/CT in terms of detection of bone metastasis in prostate cancer patients. Materials and methods: A total of 28 prostate cancer patients with bone scan and PSMA PET/CT performed within 90 days were retrospectively included in our analysis. All bone lesions were scored as negative (score-0), positive (score-1), or suspicious (score-2) for metastasis by two experienced nuclear medicine physicians. Both patient-based and region-based analyses were made for all osseous lesions. Results: On per-patient analysis; sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were 72.7%, 52.9%, 50%, 75%, and 60.7%, respectively, for bone scan and 90.9%, 100%, 100%, 94.4%, and 96.4%, respectively, for PSMA PET/CT. On per-region analysis; sensitivity, specificity, PPV, NPV, and accuracy were 76.2%, 80.9%, 57.1%, 91.1%, and 79.8%, respectively, for bone scan and 85.7%, 100%, 100%, 95.5%, and 95.4%, respectively, for PSMA PET/CT. Conclusion: Ga-68 PSMA PET/CT has higher sensitivity, specificity, and accuracy compared to bone scan in terms of bone metastasis detection in prostate cancer patients. Therefore, it might be the modality of choice for patients with suspicion for metastatic disease, despite negative bone scan and conventional imaging results

Novel treatment of 99Tc-MDP improves clinical and radiographic results for patients with osteochondral lesions of the talus.

BACKGROUND: Management of osteochondral lesions of talus (OLT) remains controversial. 99Tc-MDP, a decay product of 99mTc-MDP which is widely used for bone scan, is effective in the clinical treatment of rheumatoid arthritis. The purpose of the study is to investigate the effects of 99Tc-MDP treatment on OLT. METHODS: In the clinical evaluation, 66 patients with a total of 83 lesions of OLT who failed appropriate non-operative treatment and surgery were retrospectively included and treated with intravenous injection of 99Tc-MDP and Chinese herbal fumigation (CHF). The effects of 99Tc-MDP and CHF on OLT were evaluated by the American Orthopedic Foot and Ankle Society Ankle-Hindfoot Score (AOFAS), Visual Analog Scale (VAS), activities of daily living (Barthel Index), and MRI, 99mTc-MDP SPECT/CT and CT. Radiographic changes were also assessed by the transverse long diameter of the cyst on CT. RESULTS: At the last follow-up, AOFAS, VAS and Barthel Index improved significantly from 68.66±9.76, 3.05±0.34 and 85±8.31 to 85.4±8.31, 1.85±0.36 and 94.7±4.99 (P<0.01), respectively after one course treatment in 66 patients with OLT. Thirty one (31/66) patients had a second treatment course. Their AOFAS, VAS and Barthel Index also improved significantly after the mean follow-up of 7±2 (6-15) months. And the average diameter of the cysts decreased from 8.01±3.35 mm to 4.74±2.83 mm (P<0.01) in the 31 patients. CONCLUSIONS: The retrospective study indicates that a combination treatment of 99Tc-MDP and CHF is effective in pain relief and return of function in a short term of follow-up for patients with OLT. Our results suggest that the small cystic lesions with increased uptake of 99mTc-MDP on SPECT/CT can be well treated by 99Tc-MDP and CHF. This novel technique holds the potential to emerge as an effective conservative treatment for OLT without adverse effects. The level of evidence for 99Tc-MDP is medium for the number of patients and retrospective study.

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.

Effects and safety of 99Tc-MDP in patients with refractory ankylosing spondylitis: a 2-stage (30-week follow-up) clinical trial.

OBJECTIVES: To evaluate the clinical efficacy and safety in patients with refractory ankylosing spondylitis (AS) initiating 99Tc-MDP therapy and explore the mechanisms. METHODS: Refractory AS patients were enrolled in the clinical trial and received 99Tc-MDP treatments for 3 or 5 courses according to ASAS improvement. Efficacy and safety evaluations were conducted during the follow-up. 37 cytokines were quantified by Luminex at baseline and week 30. p-values<0.05 were considered statistically significant. RESULTS: 51 refractory AS patients were included, with 20 healthy people serving as the control group. The patients were in an active disease state (mean (SD) ASDAS 3.66 (0.83), BASDAI 4.53 (1.92)), 42(82.35%) patients had syndesmophytes. Their cytokines were significantly higher than that in the control group. After 3 courses of 99Tc-MDP treatment, 32 (62.75%) patients achieved ASAS20 improvement, 24 (47.06%) patients achieved a clinically significant improvement (ΔASDAS-CRP≥1.1). 27 patients entered the second stage to complete 5 courses of the treatment, all of whom achieved ASAS20 improvement, 18 (66.67%) patients achieved a clinically significant improvement. All clinical parameters including ASAS and ASDAS significantly improved as the treatment was continued. Cytokines also had significant down-regulation after the treatment, and the reductions had positive correlations with the improvements of disease activity. No serious adverse event was observed. CONCLUSIONS: This investigation confirmed the remarkable efficacy of 99Tc-MDP in a large number of refractory AS patients, and highlighted the mechanism by dramatic regulation on cytokines. 99Tc-MDP was safe in clinical application.

Comparison Between Tc-99m WBC SPECT/CT and MRI for the Diagnosis of Biopsy-proven Diabetic Foot Osteomyelitis.

OBJECTIVE: Magnetic resonance imaging (MRI) is the recommended diagnostic imaging technique for diabetic foot osteomyelitis (DFO), with a reported accuracy of 79%. The gold standard to diagnose osteomyelitis is bone biopsy, with a positive culture and/or histopathology findings consistent with osteomyelitis. The purposes of this study are to assess the accuracy of technetium-99m (Tc-99m) labeled white blood cell (WBC) single-photon emission computed tomography/computed tomography (SPECT/CT) hybrid imaging for diagnosing DFO confirmed by bone biopsy and to compare that to the diagnostic accuracy of an MRI. MATERIALS AND METHODS: The authors performed a retrospective chart review of 166 patients who received a bone biopsy to confirm the diagnosis of a suspected DFO at a large municipal hospital between 2010 and 2013. Patients were selected on the basis of whether they received an MRI or a SPECT/CT. Patients whose scans were not within a clinically relevant time frame of the biopsy were excluded. Imaging results were correlated with probability of osteomyelitis determined by bone biopsy. RESULTS: For inclusion criteria, 110 patients met the study's criteria: 52 SPECT/CT patients and 58 MRI patients. The sensitivity, specificity, positive predictive value, and negative predictive value of SPECT/CT were 89%, 35%, 74%, and 60%, respectively; the corresponding values for MRI were 87%, 37%, 74%, and 58%, respectively. There were no significant differences in accuracy of diagnosing DFO between imaging techniques. CONCLUSION: This data suggests that the diagnostic accuracy of SPECT/CT imaging in DFOs is similar to an MRI.

(99) Tc-methylene diphosphonate improves rheumatoid arthritis disease activity by increasing the frequency of peripheral γδ T cells and CD4(+) CD25(+) Foxp3(+) Tregs.

AIM: γδ T cells exhibit important functions in the pathogenesis of rheumatoid arthritis (RA). In recent years, numerous studies harnessed the γδ T cell-activating capacity of aminobiphosphonates for the treatment of malignant tumors. As (99) Tc-methylene diphosphonate ((99) Tc-MDP) has long been widely used for the treatment of RA in China with good efficacy, we are interested in whether this drug exerts its therapeutic effect on RA by modulating peripheral γδ T cells of RA patients. OBJECTIVES: To investigate the effect of (99) Tc-MDP on the frequency of γδ T cells and CD4(+) CD25(+) Foxp3(+) Tregs in the peripheral blood of patients with active RA. METHODS: Nineteen patients with active RA were treated with (99) Tc-MDP intravenously at a dose of 20 µg/day consecutively for 10-14 days. Before and after treatment, the main clinical and laboratory parameters for each patient were evaluated. The frequency of CD3(+) γδ(+) T cells and CD4(+) CD25(+) Foxp3(+) Tregs was detected by flow cytometry. Serum levels of interferon (IFN)-γ, tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-10 and transforming growth factor (TGF)-ß were measured with enzyme-linked immunosorbent assay. RESULTS: After intravenous (99) Tc-MDP therapy, the frequency of peripheral CD3(+) γδ(+) T cells and CD4(+) CD25(+) Foxp3(+) Tregs were significantly elevated, paralleled with decreased serum levels of TNF-α and IL-6 and increased level of serum TGF-ß. The elevation of peripheral CD3(+) γδ(+) T cells was positively correlated with increased serum TGF-ß and decreased disease activity. CONCLUSION: (99) Tc-MDP may improve the activity of RA through upregulating the frequency of peripheral γδ T cells and CD4(+) CD25(+) Foxp3(+) Tregs as well as affecting the serum cytokine environment by increasing TGF-ß and decreasing TNF-α and IL-6.

Intravitreal injection of (99)Tc-MDP inhibits the development of laser-induced choroidal neovascularization in rhesus monkeys.

BACKGROUND: The aim of this study was to investigate the safety and efficacy of intravitreal injection of (99)Tc-MDP, a decay product of (99m)Tc-MDP, on the development of laser-induced choroidal neovascularization (CNV) in rhesus monkeys. METHODS: Experimental CNV was induced by argon laser with a small high-energy laser spot. Monkeys were given 50 µL of (99)Tc-MDP at a concentration of 0.005 µg/mL (n = 6) or 0.01 µg/mL (n = 6) by intravitreal injection once a week immediately after laser injury for a period of 56 days. Control animals were treated with the same volume of PBS (n = 6) in the same way. Eyes were monitored by ophthalmic examination, color fundus photography, fluorescence fundus angiography (FFA), optical coherence tomography (OCT) and histology. Incidences of grade 4 CNV lesions as well as the leakage areas of grade 4 CNVs on the late-phase of fluorescein angiograms were measured in a standardized, randomized and masked fashion fortnightly. The maximum widths and heights of grade 4 CNVs were also calculated by histology at the end of the experiment. Toxicity of (99)Tc-MDP on the retina was evaluated by electroretinogram (ERG) and histologic analysis. RESULTS: (99)Tc-MDP reduced the incidences of grade 4 CNVs by 33.33 % and 39.40 % in the 0.005 µg/mL and 0.01 µg/mL groups, respectively, compared with the PBS group on day 28 (P < 0.05; n = 6). The leakage areas of grade 4 CNVs were smaller in the 0.005 µg/mL (0.7136 ± 0.0283 mm(2), p <0.01; n = 6) and 0.01 µg/mL (0.4351 ± 0.0349 mm(2), p < 0.01; n = 6) groups than those in the PBS control group (0.9373 ± 0.0455 mm(2); n = 6) in a dose-dependent manner on day 28. OCT and histology also showed that the sizes of CNVs were smaller in the (99)Tc-MDP treated groups than those in the PBS group. Although intravitreal injection of (99)Tc-MDP led to mild inflammatory reaction in the anterior chamber, histology and ERG findings demonstrated that (99)Tc-MDP did not cause any change in histological structure or function of the retina (p>0.05). CONCLUSIONS: Intravitreal injection of (99)Tc-MDP can inhibit the development of laser-induced CNV without toxic effect on retina, suggesting that (99)Tc-MDP has therapeutic potential for CNV related diseases.

Is bone mineral density measurement using dual-energy X-ray absorptiometry affected by gamma rays?

The objective of this study was to determine whether the gamma rays emitted from the radionuclide effect bone mineral density (BMD) measurement. Nine subjects (mean age: 56 ± 17.96 yr) scheduled for bone scanning underwent BMD measurement using dual-energy X-ray absorptiometry (DXA) (Hologic/Discovery A) before and 1, 2, and 4 h after injection of technetium-99m-methylene diphosphonate (99mTc-MDP). Ten subjects (mean age: 41 ± 15.47 yr) scheduled for therapy of differentiated thyroid carcinoma with iodine-131 underwent BMD measurement before and 2 h after therapeutic radionuclide administration. All patients were given whole body BMD measurement, including head, arm, ribs, lumbar spine, pelvis, and leg sites. Besides, patients who referred to radioiodine therapy were given total hip and femoral neck BMD measurement as well. No statistically significant changes in BMD values were detected after 99mTc-MDP and iodine-131 administration for all measurement sites (p > 0.05), and individual difference of BMD before and after radionuclide imaging or therapy was less than the least significant change in lumbar spine, total hip, and femoral neck. In conclusion, BMD measurements are not influenced by the gamma rays emitted from technetium-99m and iodine-131. DXA bone densitometry may be performed simultaneously with bone scanning and radioiodine therapy.

[Clinical nuclear medicine in bone metastases].

(99m)Tc-hydroxymethylene diphosphonate is not directly to Calcium of the bone matrix, but is binding to hydroxyapatite within the bone matrix. Strontium-89 is a member of family II A of the periodic table, same as Calcium, and is incorporated into bone matrix directly. It is very important that the the regions of the pain from bone metastases are present in the site of the abnormal uptake by bone metastases.

Predictive and prognostic value of circulating nucleosomes and serum biomarkers in patients with metastasized colorectal cancer undergoing Selective Internal Radiation Therapy.

BACKGROUND: Selective Internal Radiation Therapy (SIRT) is a new and effective locoregional anticancer therapy for colorectal cancer patients with liver metastases. Markers for prediction of therapy response and prognosis are needed for the individual management of those patients undergoing SIRT. METHODS: Blood samples were prospectively and consecutively taken from 49 colorectal cancer patients with extensive hepatic metastases before, three, six, 24 and 48 h after SIRT to analyze the concentrations of nucleosomes and further laboratory parameters, and to compare them with the response to therapy regularly determined 3 months after therapy and with overall survival. RESULTS: Circulating nucleosomes, cytokeratin-19 fragments (CYFRA 21-1), carcinoembryonic antigen (CEA), C-reactive protein (CRP) and various liver markers increased already 24 h after SIRT. Pretherapeutical levels of CYFRA 21-1, CEA, cancer antigen 19-9 (CA 19-9), asparate-aminotransferase (AST) and lactate dehydrogenase (LDH) as well as 24 h values of nucleosomes were significantly higher in patients suffering from disease progression (N = 35) than in non-progressive patients (N = 14). Concerning overall survival, CEA, CA 19-9, CYFRA 21-1, CRP, LDH, AST, choline esterase (CHE), gamma-glutamyl-transferase, alkaline phosphatase, and amylase (all 0 h, 24 h) and nucleosomes (24 h) were found to be prognostic relevant markers in univariate analyses. In multivariate Cox-Regression analysis, the best prognostic model was obtained for the combination of CRP and AST. When 24 h values were additionally included, nucleosomes (24 h) further improved the existing model. CONCLUSION: Panels of biochemical markers are helpful to stratify pretherapeutically colorectal cancer patients for SIR-therapy and to early estimate the response to SIR-therapy.

Changes observed in radionuclide bone scans during and after teriparatide treatment for osteoporosis.

PURPOSE: Visual changes on radionuclide bone scans have been reported with teriparatide treatment. To assess this, serial studies were evaluated and quantified in ten postmenopausal women with osteoporosis treated with teriparatide (20 µg/day subcutaneous) who had (99m)Tc-methylene diphosphonate (MDP) bone scans (baseline, 3 and 18 months, then after 6 months off therapy). METHODS: Women were injected with 600 MBq (99m)Tc-MDP, and diagnostic bone scan images were assessed at 3.5 h. Additional whole-body scans (10 min, 1, 2, 3 and 4 h) were analysed for (99m)Tc-MDP skeletal plasma clearance (K(bone)). Regional K(bone) differences were obtained for the whole skeleton and six regions (calvarium, mandible, spine, pelvis, upper and lower extremities). Bone turnover markers (BTM) were also measured. RESULTS: Most subjects showed visual changes on 3- and 18-month bone scan images that disappeared after 6 months off therapy. Enhanced uptake was seen predominantly in the calvarium and lower extremities. Whole skeleton K(bone) displayed a median increase of 22% (3 months, p = 0.004) and 34% (18 months, p = 0.002) decreasing to 0.7% (6 months off therapy). Calvarium K(bone) changes were three times larger than other sites. After 6 months off therapy, all K(bone) and BTM values returned towards baseline. CONCLUSION: The increased (99m)Tc-MDP skeletal uptake with teriparatide indicated increased bone formation which was supported by BTM increases. After 6 months off therapy, metabolic activity diminished towards baseline. The modulation of (99m)Tc-MDP skeletal uptake during treatment was the result of teriparatide's metabolic activity. These findings may aid the radiological evaluation of similar teriparatide patients having radionuclide bone scans.

Radionuclide therapy and integrated protocols for bone metastases.

Bone metastases are responsible for most of the morbidity and mortality associated with solid malignant tumors, occurring in about 65-70% of the patients with advanced breast or prostate cancer. The pathophysiology of skeletal metastasis is a complex process that involves several biologic process leading to cellular invasion, adhesions and stimulation of osteoclasts and osteoblasts with the mediation of several factors including cytokines, serine proteases and tumor-derived factors. The clinical management of pain from bone metastasis, which is mostly due to indirect stimulation of sensory nerve endings by cytokines and other biologically-active compounds released locally in response to the presence of tumor cells in the bone marrow, includes several options that can be used either alone or in varying combinations, such as analgesic drugs, chemo- or hormonal therapy, bisphosponates, external beam radiation therapy, and surgery. Bone-seeking radiopharmaceuticals play an important role in the treatment of pain caused by multiple blastic or mixed-type skeletal lesions; they have in general a favorable toxicity profile and a high rate of overall clinical benefit, although they may differ in terms of duration of pain palliation and suitability for repeat treatments. The palliative effect can be attributed to the radiation targeted to the bone marrow space, and the overall average response ranges between about 45-80%, with complete response in 10-30% of the cases. In selected clinical conditions, radionuclide therapy can also constitute an effective systemic treatment beyond bone pain palliation, and a synergistic anti-tumour effect can be expected by the combination with other agents, such as chemotherapy or bisphosphonates. This review summarizes the current experience with bone-seeking radiopharmaceuticals used for bone pain palliation, focusing on indications, patients' selection, efficacy and toxicity. Finally, the available data on combination therapies showing encouraging results as to potential anti-tumor efficacy are also reviewed.

[Pain palliation using unsealed radionuclides]. / Einsatz offener Radionuklide in der Schmerztherapie.

Chronic pain is one of the most frequent and distressing symptoms in patients suffering from bone metastases due to malignant disease. Besides pharmacological therapy using analgesics according to the WHO scheme and local surgical or radiotherapeutic treatment options, systemic radionuclide therapy is available, particularly for patients with multilocular metastatic disease. This palliative pain treatment is almost free of severe side effects and is thus indicated as a complementary therapy as part of an interdisciplinary approach in pain treatment. Moreover, preliminary data indicate a favorable cost:utility ratio. Positive clinical effects with marked reduction of pain are described in 70-80% of patients with breast or prostate cancer. However, complete analgesia is uncommon and, thus, most patients require analgesic treatment during the further course of their disease.

Guideline to regulations for radiopharmaceuticals in early phase clinical trials in the EU.

The purpose of this guideline is to help investigators by giving an overview of relevant current EU requirements concerning the quality of starting materials and final drug products (the radiopharmaceuticals), the non-clinical safety studies and dosimetry considerations whilst designing a human clinical trial which includes the use of radiopharmaceutical compounds.