99mTc-labeled Methylene Diphosphonate Research Articles

Radiomics‑Clinical model based on 99mTc-MDP SPECT/CT for distinguishing between bone metastasis and benign bone disease in tumor patients.

To establish a radiomics-clinical model based on 99mTc-MDP SPECT/CT for distinguishing between bone metastasis and benign bone disease in tumor patients. We retrospectively analyzed 256 patients (122 with bone metastasis and 134 with benign bone disease) and randomized them in the ratio of 6:2:2 into training, test and validation sets. All patients underwent 99mTc-labeled methylene diphosphonate (99mTc-MDP) SPECT/CT. We manually outlined the volumes of interest (VOIs) of lesions using ITK-SNAP from SPECT and CT images. In the training set, radiomics features were extracted using PyRadiomics and selected using Least Absolute Shrinkage and Selection Operator (LASSO) regression. Then, we established three radiomics models (CT, SPECT and SPECT-CT models) using support vector machine (SVM). In addition, a radiomics-clinical model was constructed using multivariable logistic regression analysis. The four models' performance was assessed using the area under the receiver operating characteristic curve (AUC). Using DeLong test to make comparisons between the ROC (receiver operating characteristic) curves of different models. The clinical utility of the models was evaluated using decision curve analysis (DCA). The radiomics-clinical displayed excellent performance, and its AUC was 0.941 and 0.879 in the training and test sets. The DCA of radiomics-clinical model showed the highest clinical utility. The radiomics-clinical nomogram for identifying bone metastasis and benign bone disease in tumor patients was suitable to assist in clinical decision.

All that illuminates on radionuclide imaging is not a metastatic lesion: Role of complementary imaging

Radionuclide imaging is a non-invasive modality based on tracer physiology widely utilized in the diagnosis, staging, therapeutic evaluation, and monitoring of metastatic disease in a spectrum of malignancies. Calcific tendinopathy is a well-recognized disorder related to the deposition of calcium hydroxyapatite crystals within tendons. We describe a patient with urothelial carcinoma of the bladder revealing increased uptake at the left hip on 99mTc labeled methylene diphosphonate scintigraphy suggesting a metastatic lesion. Cross-sectional imaging with magnetic resonance imaging confirmed the accurate diagnosis of calcific tendinopathy of gluteus maximus insertion. This case report highlights the importance of a thorough clinical evaluation and complementary imaging in assessing benign pathologies which may mimic metastatic bone lesions.

Clinical and imaging features of six Han patients with SAPHO syndrome.

Synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome is a rare autoimmune disease characterized by skin or osteoarticular damage. SAPHO syndrome is often misdiagnosed or missed diagnosis due to lack of overall understanding of the disease by clinicians. To analyze the clinical symptoms and imaging features of six Han patients with SAPHO syndrome in order to provide reference for doctors to diagnose SAPHO syndrome. This study retrospectively analyzed the clinical data of six Han patients with SAPHO syndrome. All six Han patients with SAPHO syndrome had severe acne or pustulosis of the hands and feet, and all of them had osteoarticular damage, including five cases involving the sternoclavicular joint. Some patients showed a specific and typical "bull's head" sign on 99mTc-labeled methylene diphosphonate bone imaging. Among the six patients recruited, there was one thoracic vertebra, one cervical vertebra, one sacroiliac joint, and one peripheral joint involvement. Two patients had limited activity due to severe osteoarticular damage. Due to the atypical clinical symptoms of SAPHO syndrome, most patients will experience a tortuous and long diagnostic process, while a correct understanding and timely intervention of SAPHO syndrome are essential to improve the prognosis of patients.

Added diagnostic value of SPECT to evaluate bone metastases inbreast cancer patients with normal whole body bone scan.

Background:In this research, we aimed to survey the added value of single photon emission computed tomography (SPECT) in comparison with planar whole body bone scan to visualize bone metastatic lesions in patients with breast cancer.Methods:A total of 80 patients with breast cancer (invasive ductal carcinoma) were examined with planar whole body bone scan and SPECT imaging using 99mTc-labelled methylene diphosphonate (99mTc-MDP). The patients with abnormal uptakes in SPECT imaging were also investigated with magnetic resonance imaging (MRI).Results:Among these 80 patients with normal whole body bone SPECT scan, 19 (23.25%) of them revealed abnormal 99mTc-MDP uptake in skeleton. Furthermore, these 19 patients were subjected to MRI and 3 (3.75%) of them were confirmed with metastatic bone lesion.Conclusion:The obtained data suggest that SPECT possess the added diagnostic over planar whole body bone scan.

Dosimetric considerations of 99mTc-MDP uptake within the epiphyseal plates of the long bones of pediatric patients

Skeletal scintigraphy is most performed in pediatric patients using the radiopharmaceutical 99mTc labelled methylene diphosphonate (99mTc-MDP). Reference biokinetic models for 99mTc-MDP indicate 50% of the administered activity is uniformly localized to the interior bone surfaces (trabecular and cortical regions), yet imaging data clearly show some preferential uptake to the epiphyseal growth plates of the long bones. To explore the dosimetric consequences of these regional activity concentrations, we have modified mesh-type computational phantoms of the International Commission on Radiological Protection (ICRP) reference pediatric series to explicitly include geometric models of the epiphyseal growth plates (2 mm in thickness) within the left/right, distal/proximal ends of the humeri, radii, ulnae, femora, tibia, and fibulae. Bone mineral activity from the ICRP Publication 128 biokinetic model for 99mTc-MDP (ICRP ) was then partitioned to the growth plates at values of 0.5%, 4.4%, 8.3%, 12.2%, 16.1%, and 20%. Radiation transport simulations were performed to compute 99mTc S-values and organ dose coefficients to the soft tissues and to bone site-specific regions of spongiosa. As the percentage of bone activity assigned to the growth plates was increased (from 0.5% to 20%), absorbed doses to the soft tissue organs, active bone marrow, bone endosteum (BE), as well as the detriment-weighted dose, were shown to decrease from their nominal values (no substantial growth plate activity), while epiphyseal plate self-doses increased. In the 15 year old male phantom, moving from 0.5% to 20% relative bone activity within the epiphyseal plates resulted in a 15% reduction in active marrow (AM) and BE dose, a 10% reduction in mean soft tissue and detriment-weighted dose, and a 6.3-fold increase in epiphyseal plate self-dose. In the newborn female phantom, we observed a 18% decrease in AM and BE dose, a 10% decrease in mean soft tissue dose, a 15% decrease in detriment-weighted dose, and 12.8-fold increase in epiphyseal plate self-dose. Increases (to 3 mm) and decreases (to 1 mm) in the assumed growth plate thickness of our models were shown to impact only the growth plate self-dose. Future work in differential quantification of 99mTc-MDP activity—growth plates versus other bone surfaces—is required to provide clinically realistic data on activity partitioning as a function of patient age, and perhaps skeletal site. The phantom series presented here may be used to develop more optimized age-related guidance on 99mTc-MDP administered activities to children.

Osteoblastic and hyperostotic craniofacial lesion detected by 99mTc-labeled methylene diphosphonate bone scintigraphy and single-photon emission computed tomography/computed tomography: a pictorial essay.

99mTc-bisphophonates bone scan, planar and single-photon emission computed tomography/computed tomography (SPECT/CT) modalities, is a commonly used technique that provides high sensitivity and specificity for detection of osseous metastases. However, besides bone metastases, SPECT/CT provides an accurate evaluation of the localization of the lesions and supplies anatomic information that can be valuable for diagnosis of nonmalignant bone diseases, occasionally disclosed in the skull. Reporting of craniofacial lesions detected by 99mTc-MDP (99mTc-labeled methylene diphosphonate) bone scintigraphy and SPECT/CT in the literature is limited. The aim of this pictorial review is to present the findings detected by 99mTc-MDP bone scintigraphy and SPECT/CT including cases under two broad categories: osteoblastic and hyperostosis craniofacial lesions.

Evaluating disease activity in patients with ankylosing spondylitis and rheumatoid arthritis using 99mtc-glucosamine.

To evaluate the clinical utility of a novel radiotracer, 99mTc-glucosamine, in assessing disease activity of both rheumatoid arthritis (RA) and ankylosing spondylitis (AS). Material and Methods: Twenty-five patients with RA (nine males and 16 females) and 12 patients with AS (all male) at various stages of disease were recruited for the study. A clinical history and examination was performed, followed by the measurement of hematological, biochemical, and autoimmune serological parameters to assess disease activity. 99mTc-glucosamine was intravenously administered and scans were compared with other imaging modalities, including plain X-ray, magnetic resonance imaging (MRI), and bone scans. In patients with AS, 99mTc-glucosamine scans were more capable of identifying active disease and differentiating between inflammatory and non-inflammatory causes. In patients with RA, 99mTc-glucosamine accumulated at all known sites of disease involvement. Uptake was most pronounced in patients with active untreated disease. The relative tracer activity in the involved joints increased with time compared with that in the adjoining soft tissue, liver, and cardiac blood pool. Using Spearman's correlation coefficient, there was a positive correlation among glucosamine scan scores, C-reactive protein (p=0.048), and clinical assessment (p=0.003), which was not noted with bone scans. The radiotracer was well tolerated by all patients, with no adverse reactions. 99mTc-glucosamine imaging could detect spinal inflammation in AS. With respect to RA, 99mTc-glucosamine was a viable alternative to 99mTc-labeled methylene diphosphonate nuclear bone scans for imaging inflamed joints and had the added advantage of demonstrating a significant clinical correlation between disease activity and scan findings.

Prospective study evaluating the relative sensitivity of 18F-NaF PET/CT for detecting skeletal metastases from renal cell carcinoma in comparison to multidetector CT and 99mTc-MDP bone scintigraphy, using an adaptive trial design

BackgroundThe detection of occult bone metastases is a key factor in determining the management of patients with renal cell carcinoma (RCC), especially when curative surgery is considered. This prospective study assessed the sensitivity of 18F-labelled sodium fluoride in conjunction with positron emission tomography/computed tomography (18F-NaF PET/CT) for detecting RCC bone metastases, compared with conventional imaging by bone scintigraphy or CT. Patients and methodsAn adaptive two-stage trial design was utilized, which was stopped after the first stage due to statistical efficacy. Ten patients with stage IV RCC and bone metastases were imaged with 18F-NaF PET/CT and 99mTc-labelled methylene diphosphonate (99mTc-MDP) bone scintigraphy including pelvic single photon emission computed tomography (SPECT). Images were reported independently by experienced radiologists and nuclear medicine physicians using a 5-point scoring system. ResultsSeventy-seven lesions were diagnosed as malignant: 100% were identified by 18F-NaF PET/CT, 46% by CT and 29% by bone scintigraphy/SPECT. Standard-of-care imaging with CT and bone scintigraphy identified 65% of the metastases reported by 18F-NaF PET/CT. On an individual patient basis, 18F-NaF PET/CT detected more RCC metastases than 99mTc-MDP bone scintigraphy/SPECT or CT alone (P = 0.007). The metabolic volumes, mean and maximum standardized uptake values (SUVmean and SUVmax) of the malignant lesions were significantly greater than those of the benign lesions (P < 0.001). Conclusions18F-NaF PET/CT is significantly more sensitive at detecting RCC skeletal metastases than conventional bone scintigraphy or CT. The detection of occult bone metastases could greatly alter patient management, particularly in the context when standard-of-care imaging is negative for skeletal metastases.

Irradiation parameters play a crucial role in the (n, γ) production of 170Tm suitable for clinical use in bone pain palliation

While neutron activation of natural Tm2O3 is the convenient strategy for producing 170Tm for use in palliative care of painful bone metastases, the coproduction of 171Tm (t ½ = 1.92 years) is as an impediment towards its clinical utility. The production strategy has been optimized to obtain 170Tm with adequate specific activity and radionuclidic purity. Preliminary clinical studies carried out using the 170Tm-labeled ethylenediaminetetramethylene phosphonic acid (170Tm-EDTMP) showed site specific localization of the radiopharmaceutical in skeleton with preferential accumulation in metastatic lesions along with almost no accumulation in non-target organs, a distribution pattern comparable to that of 99mTc-labeled methylene diphosphonate (99mTc-MDP).

Prediction of bone loss in elderly women using bone turnover markers

Osteoporosis related fractures are common in old age and over 40 % of the women above 50 years of age are at a risk of developing a fragility fracture. Biochemical markers of bone turnover (BTMs) have proven to be of some value in fracture predictability. There is also a correlation between rate of decrease of areal bone mineral density (aBMD) and incident fractures. In this series of studies, the correlation between BTMs and rate of bone loss (change of aBMD and ultrasound variables) over 5 years was investigated in a cohort of 75 year-old Swedish women. In addition, correlation of BTMs and bone metabolism, as assessed by scintigraphy, was tested in postmenopausal women. Finally, the effect of precision error on the longitudinal monitoring of change in aBMD was assessed in elderly women and in elderly men. There was a strong correlation between all bone turnover markers and the results of scintigraphy (total skeletal uptake of 99mTc-labelled methylene diphosphonate), with no significant difference between bone formation markers and bone resorption markers. BTMs correlated to the 5-year rate of change of aBMD, especially in the legs and the total body, and 5 year change in speed of ultrasound. When serial measurements of BTMs were analysed, the mean value of measurements correlated more strongly to aBMD change than single measurements, and women with constantly high levels of BTMs had higher rates of bone loss. Precision error of aBMD measurement by dual-energy X-ray absorptiometry has an influence on the detection of individuals with aBMD change exceeding the least significant level. The calculated follow-up interval for detection of aBMD change beyond the least significant level in more than 50% of elderly individuals ranged from 332 years, and was dependent on the equipment used and the skeletal site tested. These results indicate that BTMs are associated with future bone loss although the correlations may not be strong enough to predict bone loss at individual level. DXA also has some limitations when used in longitudinal follow up of elderly individuals. DXA is therefore of limited use in the longitudinal monitoring ofbone loss. Further studies with novel bone turnover markers may improve the ability of BTMs to predict bone loss.

Diagnostic accuracy of 18F-fluoride PET and PET/CT in patients with bone metastases: a systematic review and meta-analysis update

This article was conducted to review the diagnostic performance of 18F-fluoride PET or PET/CT compared with planar bone scintigraphy (BS) or planar BS plus SPECT with 99mTc-labeled methylene diphosphonate in evaluating patients with metastatic bone tumor, updating a previous meta-analysis on this topic. We performed an updated meta-analysis of all available studies addressing the diagnostic accuracy of 18F-fluoride PET, 18F-fluoride PET/CT, planar BS, and planar BS plus SPECT for detecting metastatic bone tumor. The Medline (from 1966 to November, 2012), SCOPUS, and Biological Abstracts databases were searched using a search algorithm based on combinations of the terms: (1) 18F-fluoride, 18F- fluoride PET, or 18F-fluoride PET/CT, (2) bone scintigraphy, (3) bone metastasis, metastatic bone tumor, without language restriction. We constructed summary receiver operating characteristic curves using hierarchical regression models. Effective dose and cost-effectiveness, estimated from the data of the enrolled studies, were also compared between 18F-fluoride PET or PET/CT and planar BS or planar BS plus SPECT. Comparison of all the studies with data on 18F-fluoride PET or PET/CT showed sensitivity and specificity values of 91.9- and 97.1 % on patient-based analyses and 83.3 and 86.8 % on lesion-based analyses. The Az values of 18F-fluoride PET or PET/CT were 0.987 on a patient basis and 0.894 on a lesion basis, whereas those of BS or BS plus SPECT were 0.867 on a patient basis and 0.854 on a lesion basis. However, 18F-fluoride PET or PET/CT showed poorer estimated effective dose and average cost-effectiveness ratio when compared with the values recorded for planar BS or planar BS plus SPECT. 18F-fluoride PET or PET/CT showed excellent diagnostic performance for the detection of metastatic bone tumor, but the estimated effective dose and the average cost-effectiveness ratio were poorer than the values recorded with planar BS or planar BS plus SPECT. The question of whether there is an incremental diagnostic improvement with 18F-fluoride PET or PET/CT for bone metastasis should be addressed, as should the issues of radiation dose, cost-effectiveness, and potential complications against the yield of information.

Chronic mandibular osteomyelitis with suspected underlying synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome: a case report

Chronic mandibular osteomyelitis is an intractable disease. In recent years, some case reports have related this disease process to synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome, which is chronic with frequent remissions and exacerbations. This report describes a case of chronic mandibular osteomyelitis suspected to be SAPHO syndrome. A 68-year-old woman presented with pain on the left side of the mandible. On the basis of clinical and radiological findings, chronic mandibular diffuse sclerosing osteomyelitis was initially diagnosed. We administrated oral clarithromycin (400 mg daily) and levofloxacin (500 mg daily), and her pain subsequently resolved. On 99mTc-labeled methylene diphosphonate scintigraphy, tracer uptake in the asymptomatic mandible was unchanged, but there was increasing tracer uptake in the sternocostal and sternoclavicular joints, compared with 99mTc-labeled methylene diphosphonate scintigraphic findings of the first visit. We diagnosed SAPHO syndrome and administrated oral sodium risedronate hydrate (2.5 mg daily). Although there has been no pain or swelling in the area of the left mandibular lesion, we have followed up on other skin and osteoarticular manifestations in conjunction with other medical departments.

Synthesis and evaluation of a novel 68Ga-chelate-conjugated bisphosphonate as a bone-seeking agent for PET imaging

(68)Ga is a positron-emitting nuclide that has significant imaging potential given that, unlike cyclotron-produced (18)F, the isotope can be produced on-site utilizing a (68)Ge/(68)Ga generator. We recently synthesized a novel bone-seeking agent by coupling a bisphosphonate with the (68)Ga chelator 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA). This study presents a first report on the potential of this (68)Ga bone-seeking radiopharmaceutical in the detection of bone metastases. 4-Amino-1-hydroxybutylidene-1,1-bisphosphonate was conjugated with 2-[4,7-di(carboxymethyl)-1,4,7-triazonan-1-yl]pentanedioic acid, yielding 2-[4,7-di(carboxymethyl)-1,4,7-triazonan-1-yl]-5-[(4-hydroxy-4,4-diphosphonobutyl)amino]-5-oxopentanoic acid (NOTA-BP). (68)Ga-labeled NOTA-BP ([(68)Ga]NOTA-BP) was prepared by complexation of NOTA-BP with [(68)Ga] gallium chloride and evaluated in in vitro experiments, biodistribution experiments and micro-positron emission tomography (PET) imaging experiments. The labeling of NOTA-BP with (68)Ga was completed by heating for 10 min. [(68)Ga]NOTA-BP was determined to have a radiochemical purity of over 95%, a high affinity for hydroxyapatite and a high stability in plasma. In in vivo biodistribution experiments, [(68)Ga]NOTA-BP demonstrated high bone uptake potential. Compared with (99m)Tc-labeled methylene diphosphonate ([(99m)Tc]MDP) and [(18)F]fluoride, [(68)Ga]NOTA-BP exhibited faster blood clearance and a higher bone-to-blood ratio. In addition, mouse model bone metastasis was detected by micro-PET imaging at 1 h postinjection of [(68)Ga]NOTA-BP. We have developed a novel (68)Ga-radiolabeled bone-seeking agent. This [(68)Ga]NOTA-BP complex was found to have a high bone affinity and rapid blood clearance, and may thus prove to be useful as a bone-seeking agent for clinical PET.

Development and validation of an anion-exchange HPLC method for the determination of fluoride content and radiochemical purity in [18F]NaF

(18)F-labeled sodium fluoride ([(18)F]NaF) is a useful bone imaging agent that has been demonstrated to be significantly more accurate than (99m)Tc-labeled methylene diphosphonate for the detection of both sclerotic and lytic lesions in various malignancies. A reliable anion-exchange HPLC method equipped with suppressed conductivity and radioactive detectors has been developed in order to analyze the content of NaF and radiochemical purity in [(18)F]NaF radiopharmaceuticals. The method described for fluoride analysis uses an isocratic elution of NaF in a Hamilton anion-exchange column using a mobile phase that consists of 7.5 mM sodium carbonate and 0.018 mM potassium thiocyanate. The flow rate was 1.0 ml/min. The method was validated in accordance with several parameters, including system suitability, specificity, precision, accuracy, linearity, robustness, limit of detection and limit of quantification. The results are described as follows: (1) The system suitability includes the tailing factor, theoretical plate number and resolution, which are 1.192534, 2729.6594 and 16.7415, respectively. (2) For specificity, the solvent peak and chloride ion did not interfere with the retention time of the fluoride. (3) The percentage coefficient of variation for analysis of precision, including repeatability and intermediate precision, is less than 2.0%. (4) Accuracy of method is within the range of 98%-102%. (5) The range of linearity is from 10 to 400 μg/ml, with the correlation coefficient (R(2)) always being above 0.9985. (6) The data of method robustness are within acceptance criteria. (7) The limit of detection and limit of quantification are 0.0678 and 0.20 μg/ml, respectively. All of the analysis results demonstrate that this method is highly sensitive, convenient, specific and suitable for quantification of NaF over a wide linear range. Therefore, the method can be successfully performed for routine analysis of fluoride content in [(18)F]NaF radiopharmaceuticals and reduce the time required for analysis.

Bone turnover markers are correlated with total skeletal uptake of 99mTc-methylene diphosphonate (99mTc-MDP)

BackgroundSkeletal uptake of 99mTc labelled methylene diphosphonate (99mTc-MDP) is used for producing images of pathological bone uptake due to its incorporation to the sites of active bone turnover. This study was done to validate bone turnover markers using total skeletal uptake (TSU) of 99mTc-MDP.Methods22 postmenopausal women (52–80 years) volunteered to participate. Scintigraphy was performed by injecting 520 MBq of 99mTc-MDP and taking whole body images after 3 minutes, and 5 hours. TSU was calculated from these two images by taking into account the urinary loss and soft tissue uptake. Bone turnover markers used were bone specific alkaline phosphatase (S-Bone ALP), three different assays for serum osteocalcin (OC), tartrate resistant acid phosphatase 5b (S-TRACP5b), serum C-terminal cross-linked telopeptides of type I collagen (S-CTX-I) and three assays for urinary osteocalcin (U-OC).ResultsThe median TSU of 99mTc-MDP was 23% of the administered activity. All bone turnover markers were significantly correlated with TSU with r-values from 0.52 (p = 0.013) to 0.90 (p < 0.001). The two resorption markers had numerically higher correlations (S-TRACP5b r = 0.90, S-CTX-I r = 0.80) than the formation markers (S-Total OC r = 0.72, S-Bone ALP r = 0.66), but the difference was not statistically significant. TSU did not correlate with age, weight, body mass index or bone mineral density.ConclusionIn conclusion, bone turnover markers are strongly correlated with total skeletal uptake of 99mTc-MDP. There were no significant differences in correlations for bone formation and resorption markers. This should be due to the coupling between formation and resorption.

Bone imaging in prostate cancer

Bone metastases of solid tumors are common, and about 80% of them occur in patients with breast, lung or prostate cancer. Bone metastases can be suspected clinically and by laboratory tests; however, a final diagnosis relies on radiographic evidence. Bone metastases of prostate cancer usually have osteoblastic characteristics, manifested by pathological bone resorption and formation. Conventional bone scans (e.g. with (99m)Tc-labeled methylene diphosphonate) are preferred to plain-film radiography for surveillance of the entire skeleton. Radiologic diagnosis of bone metastases, particularly in patients with low burden of disease, is difficult because noncancerous bone lesions that mimic cancer are common. Conventional bone scans are limited by their low sensitivity and high false-negative rate (up to 40%) compared with advanced bone-imaging modalities such as PET, PET-CT and MRI, which might assist or replace conventional scanning methods. The correct diagnosis of bone involvement in prostate cancer is crucial to assess the effects of therapy on the primary tumor, the patient's prognosis, and the efficacy of bone-specific treatments that can reduce future bone-associated morbidity. In addition, predictive tools such as nomograms enable the identification of patients at risk of bone involvement during the course of their disease. Such tools may limit treatment costs by avoidance of unnecessary tests and might reduce both short-term and long-term complication rates.

Positron emission tomography scans for distinguishing between osteomyelitis and infarction in sickle cell disease

In a recently published review on bone involvement in sickle cell disease Almeida and Roberts (2005) reported that differentiation between bone infarction and osteomyelitis in sickle cell patients remains a diagnostic problem. Differentiation is essential because of the risk of the under-treatment of osteomyelitis. The clinical features of vaso-occlusive crisis are often comparable to osteomyelitis. In both vaso-occlusive crises and osteomyelitis, patients complain of pain and tenderness on palpation of the involved bone. A periosteal reaction resulting in swelling and erythema can occur in both conditions. Differentiation is usually not possible solely on clinical signs. When osteomyelitis is suspected, imaging of the affected area could help to support the diagnosis. Nuclear imaging, such as bone scintigraphy with 99mTc-labelled methylene diphosphonate, is highly sensitive for many active benign and malignant bone disorders. Therefore, it plays an important role in the evaluation of osteomyelitis, especially in acute osteomyelitis. In chronic osteomyelitis, the uptake of bone-seeking tracers is rather poor and non-specific. Radiolabelled white blood cells are commonly used to visualise infection or inflammation. In sickle cell disease, however, it has been shown that leucocyte scans cannot reliably discriminate between sickle cell vaso-occlusive crises and osteomyelitis. Magnetic resonance imaging (MRI) can display abnormal periosteal swelling but also fails to discriminate between infarction and infection. In a recent effort to discriminate between vaso-occlusive crises and osteomyelitis of the mandible in a known sickle cell patient, a three-phase bone scan was performed. The patient's complaints were pain in the mandibular angle with tenderness on palpation on the left side and a numb left lower lip for more than 3 weeks. These clinical signs were highly suspicious of a vaso-occlusive crisis or osteomyelitis. The bone scan showed slightly increased uptake in the left mandible area and some inhomogeneous uptake in the skull. A leucocyte scan could not be completed because the in vitro separation procedure of leucocytes from red blood cells and platelets before labelling from the patient's blood sample was not successful. Since the complaints of the patient did not resolve, further attempts were made to determine the nature of his complaints. 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) was used to establish the presence of inflammation. In areas of inflammation or infection, a high glucose metabolism is present, which results in an accumulation of the glucose analogue FDG. The FDG-PET showed a remarkably high intensive hot spot in the left mandible and no other hot spots in the rest of the skull (Fig 1). The intensity of this spot did not correspond to the intensity of the spot on the bone scan. To verify the finding of the FDG-PET scan a second PET scan was performed using 18F-NaF. This type of PET scan displays bone remodelling processes comparable to bone scans, but with a higher spatial resolution. The 18F-NaF is incorporated in hydroxyapatite of the bone and its accumulation is dependent on the regional blood flow and the osteoblastic activity (Cook & Fogelman, 2002). The 18F-NaF PET scan showed multiple inhomogeneous spots in the skull, mainly in concurrence with the bone scan. An intense hot spot was seen in the left mandible, the intensity of which was comparable to the 18F-FDG PET scan. The findings on the PET scans supported the diagnosis of osteomyelitis. One week after with the commencement of antibiotics an abscess developed at the painful site of the mandible. Various scan results of the patient. (A) 99mTc bone scan with increased uptake at the mandible. (B) 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) scan showing a single hot spot at the left mandible. Frontal (C) and lateral (D) views of a NaF PET scan showing multiple areas of infarction/remodelling in the skull and one intense hot spot in the left mandible corresponding to the single hot spot in FDG-PET scan, as depicted in B. In this particular case, PET scans helped to discriminate between infarction and inflammation or infection. It is therefore suggested that, when a distinction between infarction and infection is required and bone scintigraphy or a leucocyte scan is not conclusive, FDG-PET imaging could be considered.

The effect of intermittent pneumatic compression on the bone uptake of 99mTc-labelled methylene diphosphonate in the lower limb

Venous compression of the lower limbs will obstruct outflow through the deep and superficial veins, yet inflow will continue, without continual swelling of the limb. It is hypothesised that venous channels in the long bones act as collateral channels to restore outflow, and therefore general blood flow through bone will increase. Such a hemodynamic change should affect the uptake of radiopharmaceuticals by the bone, though uptake changes in themselves would not definitely indicate flow changes. The purpose of this study, therefore, was to determine whether bone uptake in the lower limb is affected by intermittent venous compression, irrespective of the mechanism involved. The effect of intermittent pneumatic compression of the thigh and calf on the uptake of (99m)Tc-methylene diphosphonate (MDP) was studied in 24 patients. All were undergoing routine bone imaging for medical conditions that were not focused on their lower limbs, and received 1 h of the therapy at 60 mmHg on one limb only, after injection of the radiopharmaceutical. Three hours after injection the relative difference in uptake (net counts per pixel) between the two limbs was calculated. The standard imaging protocol was otherwise unchanged. The median differences in uptake in the intermittently compressed limb compared with the contralateral limb were +7.6% (interquartile range +3.9% to +16.0%, p<0.0005 [Wilcoxon]) for the anterior aspect of the femur; +11.7% (interquartile range +4.3% to +22.2%, p<0.0005) posterior, femur; +10.5% (interquartile range +6.5% to +13.8%, p<0.0005) anterior, tibia; +10.6% (interquartile range +5.5% to +17.6%, p<0.0005) posterior, tibia. Intermittent pneumatic compression clearly and significantly increased the uptake of (99m)Tc-MDP in long bones. These data are consistent with increases in blood flow through bone, though a direct mechanical influence on the bone cannot be excluded. This effect should be given consideration during routine therapeutic and thromboprophylactic use of intermittent compression, and if the mechanism of the uptake changes can be established, their possible clinical uses should be investigated.

Multiple tracer studies of bone uptake of 99mTc-MDP and 85Sr

Multiple tracer outflow dilution studies were performed on the normal canine tibia. In all cases 125I-labeled albumin was used as a vascular tracer. In one series of experiments 99mTc-labeled methylene diphosphonate and [14C]sucrose were used as test tracers, and in a second series 85Sr and 22Na were used. A bolus of three tracers was injected into the tibial nutrient artery, and fractional concentrations appearing in the ipsilateral femoral vein were measured for a period of 5 min. A distributed model, containing parameters for capillary and bone permeability and apparent volumes of distribution of interstitial fluid, was fitted to these data. It was found that there was no discrimination between movement of 85Sr or 22Na from interstitial fluid space into bone. Transcapillary exchange does not appear to be a significant barrier to exchange between blood and bone surfaces.

Dual tracer resorption and apposition in a rat fracture model

The simultaneous measurement of tracer resorption and apposition in a rat fracture model was accomplished with 99mTc labeled methylene diphosphonate ( 99mTc-MDP) and 125I labeled phenylphosphonic acid ( 125I-øPA), respectively. Loss of 125I-øPA from the fracture site showed a biexponential release pattern; I = 31% ( t 1 2b = 2.0 d ) and II = 69% ( t 1 2b = 55.4 d ). 99mTc MDP temporal apposition at the fracture site followed the law of allometric growth ( y = bx k ) with k = 7.75, 10 days post injury. The 125I-øPA loss differed significantly ( P < 0.001) when compared to normal bone which exhibits a monoexponential release with a t 1 2b = 962 days. In the rat tibia fracture model investigated, bone apposition significantly ( P < 0.001) dominates over bone resorption as a function of time. This overwhelming difference partially accounts for the healing process. The apposition-resorption comparison may be a useful index for following the course of skeletal pathology for a variety of model systems.