18F-fluoride Positron Emission Tomography Research Articles

Validation of image-derived arterial input functions at the femoral artery using 18F-fluoride positron emission tomography

The use of image-derived arterial input functions (IDAIF) for the dynamic quantification of bone metabolism using 18F-fluoride positron emission tomography 18F-PET is an attractive alternative to direct arterial blood sampling. (a) To validate a method for obtaining the IDAIF by imaging the femoral artery against a method for deriving the IDAIF at the aorta that was previously validated against direct arterial sampling. (b) To compare the accuracy of bone plasma clearance measurements (Ki) at the total hip site obtained using the femoral artery IDAIF against Ki values at the same site obtained using the aorta IDAIF. Twelve healthy postmenopausal women with a mean age of 62.6 years (range, 52.3-70.6 years) had 60-min dynamic 18F-PET scans of the lumbar spine and proximal femur 2 weeks apart. The femoral artery IDAIF was obtained from the proximal femur scan using four different algorithms: (a) fixed partial volume correction (PVC) method; (b) variable PVC method; (c) Chen method; and (d) Cook-Lodge method. The aorta IDAIF was obtained from the lumbar spine scan using a previously validated method and the respective Ki values in the hip were used to assess the performance of each of the femoral artery algorithms. When the femoral artery IDAIF methods were compared with the aorta IDAIF in terms of the area under the curve AUC values calculated in 4-min time intervals over 0-60 min, the absolute root mean square errors were: (a) fixed PVC, 0.52; (b) variable PVC, 0.54; (c) Chen, 0.72; and (d) Cook-Lodge, 0.49 in MBq s/ml. There were small, but statistically significant differences, in the Ki values found by all four femoral artery IDAIF methods when compared with the figures obtained using the aorta IDAIF. Bland-Altman plots of Ki values showed the best agreement for the fixed PVC method with a standard deviation of 0.0020 ml/min/ml, followed by variable PVC, Cook-Lodge and Chen method with standard deviations of 0.0022, 0.0024 and 0.0042 ml/min/ml, respectively. We have demonstrated that it is possible to measure regional bone turnover at the hip without the need to perform direct arterial sampling to acquire the arterial input function (AIF). The differences in the Ki values obtained at the hip by using aorta IDAIF and any of the four image-based AIF methods at the femoral artery were small and clinically insignificant. The performance of fixed PVC, variable PVC and Cook-Lodge method was similar although the latter was less robust than the other two methods.

Use of 18F-fluoride PET to determine the appropriate tissue sampling region for improved sensitivity of tissue examinations in cases of suspected periprosthetic infection after total hip arthroplasty

Background and purpose The accurate diagnosis of periprosthetic infection requires assessment of intraoperative tissues. These must be sampled from the appropriate sites.We used 18F-fluoride positron emission tomography (PET) to identify sites of inflammation in order to improve the sensitivity of histopathology, microbiological culture, and real-time PCR in total hip arthroplasty (THA) patients.Patients and methods 23 THA patients (23 hips) scheduled for revision surgery (the revision group) and 17 uninfected THA patients (23 hips; control group) were enrolled. Uptake was classified into major, minor, and no uptake. To evaluate the association between the 18F-fluoride uptake and intraoperative tissue results in the revision group, we calculated their sensitivity on each of the major, minor, and no-uptake sides.Results 17 revision patients showed major uptake and all were diagnosed as having septic loosening from intraoperative tissue results. Minor uptake was observed in the other 6 revision patients and all were diagnosed as having aseptic loosening. Apart from 3 cases that showed minor uptake regions, control subjects showed no uptake. In the revision group, the sensitivities of histopathology, microbiological culture, real-time PCR separately and also in combination were 0.78, 0.58, 0.96, and 0.96, respectively, on the major 18F-fluoride uptake sides, 0.0, 0.0, 0.1, and 0.1 on the minor-uptake sides, and 0, 0, 0.18, and 0.18 on the no-uptake sides.Interpretation Our findings suggest that preoperative assessment of major uptake of 18F-fluoride markedly improves the accuracy of tissue sampling, and thus the sensitivity of subsequent tissue examinations. More definitive diagnosis of periprosthetic infection is therefore possible.

Radionuclide studies of bone metabolism: Do bone uptake and bone plasma clearance provide equivalent measurements of bone turnover?

Quantitative radionuclide imaging using (18)F-fluoride positron emission tomography (18F-PET) or (99m)Tc-methylene diphosphonate ((99m)Tc-MDP) bone scans provides a novel tool for studying regional and whole skeleton bone turnover that complements the information provided by biochemical markers. Radionuclide bone scans can be quantified by measuring either tracer uptake or, if blood sampling is performed, bone plasma clearance. This study examines whether these two methods provide equivalent information about bone turnover. We examined data from two clinical trials of the bone anabolic agent teriparatide. In Study 1 twenty osteoporotic women had 18F-PET scans of the lumbar spine at baseline and after 6 months treatment with teriparatide. Bone uptake in the lumbar spine was expressed as standardised uptake values (SUV) and blood samples taken to evaluate plasma clearance. In Study 2 ten women had (99m)Tc-MDP scans at baseline, 3 and 18 months after starting teriparatide. Blood samples were taken and whole skeleton plasma clearance and bone uptake calculated. In Study 1 spine plasma clearance increased by 23.8% after 6-months treatment (P=0.0003), whilst SUV increased by only 3.0% (P=0.84). In Study 2 whole skeleton plasma clearance increased by 37.1% after 18-months treatment (P=0.0002), whilst the 4-hour whole skeleton uptake increased by only 25.5% (P=0.0001). During treatment the 18F- plasma concentration decrease by 20% and (99m)Tc-MDP concentration by 13%, and these latter changes were sufficient to explain the differences between the uptake and plasma clearance results. Measurements of response to treatment using bone uptake and plasma clearance gave different results because the effects of teriparatide on bone resulted in a sufficiently increased demand for radionuclide tracer from the skeleton that the concentration in the circulation decreased. Similar effects may occur with other therapies that have a large enough effect on bone metabolism. In these circumstances changes in bone plasma clearance give a truer impression of response to treatment than those in SUV or uptake.

Validation of new image-derived arterial input functions at the aorta using 18F-fluoride positron emission tomography

(i) To validate two new image-based methods for finding the plasma arterial input function (AIF) and evaluate the performance of these and two similar techniques against arterial sampling. (ii) To evaluate the performance of all four image-derived AIF (IDAIF) methods against arterial sampling for measuring the F plasma clearance (Ki) to the lumbar spine. Eight healthy postmenopausal women had a F-fluoride positron emission tomography scan of the lumbar spine. Venous blood samples were used to estimate the IDAIFs from: (i) a fixed population-based partial volume correction (PVC) factor method, (ii) a variable PVC factor method, (iii) the Chen method, and (iv) the Cook-Lodge method. Continuous arterial sampling and the respective Ki values were used as the gold standard against which the performance of the IDAIF methods was compared. The IDAIFs were compared with direct arterial sampling in terms of the area under the curve values. The percentage root mean square error in area under the curves compared with arterial sampling were: (i) fixed PVC: 12.7%, (ii) variable PVC: 12.0%, (iii) Chen: 39.0%, and (iv) Cook-Lodge: 17.3%. There were small but significant differences in the Ki values found by all four methods compared with arterial sampling. Bland-Altman plots of Ki values showed the best agreement for the variable and fixed PVC methods with a standard deviation of 0.0026 and 0.0030 ml/min/ml, respectively. The differences in the Ki values obtained at the lumbar spine using direct arterial sampling and any of the IDAIF methods at the aorta were clinically nonsignificant. The variable PVC and fixed PVC methods performed better than the Cook-Lodge and Chen methods.

Bone turnover at the spine and hip measured using 18F-PET

Bone turnover at the spine and hip measured using 18F-PET

18F-fluoride PET: changes in uptake as a method to assess response in bone metastases from castrate-resistant prostate cancer patients treated with 223Ra-chloride (Alpharadin).

A qualitative assessment of conventional bone scintigraphy with 99mTc methylene diphosphonate is perceived as an insensitive method for monitoring the treatment response of bone metastases, and we postulated that semi-quantitative 18F-fluoride positron emission tomography (PET) might serve as a suitable alternative biomarker of the treatment response. Five patients with castrate-resistant prostate cancer and bone metastases with no known soft tissue disease received 100 kBq/kg of radium-223 (223Ra)-chloride (Alpharadin) therapy at 0 and 6 weeks and had whole body 18F-fluoride PET scans at baseline, 6 and 12 weeks with concurrent prostatic-specific antigen (PSA) and alkaline phosphatase (ALP) measurements. A qualitative comparison of the PET scans was performed blinded to the PSA and ALP results. A semi-quantitative comparison was made by measuring the maximum standardised uptake values (SUVmax) in five bone metastases in each patient. The means of the five SUVmax measurements in each subject were used as a quantitative measure of global metastatic activity at each time point. Three patients showed a PSA decline at 12 weeks (-44%, -31%, -27% reduction) whilst two patients showed PSA increases (+10%, +17%). All five patients showed a reduction in ALP of greater than 25%. The qualitative assessment of the 18F-fluoride scans recorded a stable disease in each case. However, the semi-quantitative assessment showed agreement with the PSA decline in three patients (-52%, -75%, -49%) and minimal change (+12%, -16%) in two patients with increased PSA at 12 weeks. Four patients showed similar reductions in mean SUVmax and ALP at 12 weeks. The semi-quantitative 18F-fluoride PET is more accurate than the qualitative comparison of scans in assessing response in bone metastases, correlating with the PSA response and ALP activity and offering a potential imaging biomarker for monitoring treatment response in bone metastases following treatment with 223Ra-chloride.

A meta-analysis of 18F-Fluoride positron emission tomography for assessment of metastatic bone tumor

The aim of this study was to assess the diagnostic performance of (18)F-Fluoride positron emission tomography (PET) or positron emission tomography/computed tomography (PET/CT) compared with bone scintigraphy (BS) planar or BS planar and single photon emission computed tomography (SPECT) in evaluating patients with metastatic bone tumor. We performed a meta-analysis of all available studies addressing the diagnostic accuracy of (18)F-Fluoride PET, (18)F-Fluoride PET/CT, BS planar, and BS planar and SPECT for detecting the metastatic bone tumor. We determined sensitivities and specificities across studies, calculated positive and negative likelihood ratios, and drew summary receiver operating characteristic curves using hierarchical regression models. We also compared the effective dose and cost-effectiveness estimated by data from the enrolled studies between (18)F-Fluoride PET or PET/CT and BS planar or BS planar and SPECT. When comparing all studies with data on (18)F-Fluoride PET or PET/CT, sensitivity and specificity were 96.2% [95% confidence interval (CI) 93.5-98.9%] and 98.5% (95% CI 97.0-100%), respectively, on a patient basis and 96.9% (95% CI 95.9-98.0%) and 98.0% (95% CI 97.1-98.9%), respectively, on a lesion basis. The Az values of (18)F-Fluoride PET or PET/CT were 0.986 for the patient basis and 0.905 for the lesion basis, whereas those of BS or BS and SPECT were 0.866 for the patient basis and 0.854 for the lesion basis. However, the estimated effective dose and average cost-effective ratio were poorer for (18)F-Fluoride PET or PET/CT than those of BS planar or BS planar and SPECT. (18)F-Fluoride PET or PET/CT has excellent diagnostic performance for the detection of metastatic bone tumor, but the estimated effective dose and average cost-effective ratio are at a disadvantage compared with BS planar or BS planar and SPECT.

Noninvasive methods of measuring bone blood perfusion

Measurement of bone blood flow and perfusion characteristics in a noninvasive and serial manner would be advantageous in assessing revascularization after trauma and the possible risk of avascular necrosis. Many disease states, including osteoporosis, osteoarthritis, and bone neoplasms, result in disturbed bone perfusion. A causal link between bone perfusion and remodeling has shown its importance in sustained healing and regrowth following injury. Measurement of perfusion and permeability within the bone was performed with small and macromolecular contrast media, using dynamic contrast-enhanced magnetic resonance imaging in models of osteoarthritis and the femoral head. Bone blood flow and remodeling was estimated using (18)F-Fluoride positron emission tomography in fracture healing and osteoarthritis. Multimodality assessment of bone blood flow, permeability, and remodeling by using noninvasive imaging techniques may provide information essential in monitoring subsequent rates of healing and response to treatment as well as identifying candidates for additional therapeutic or surgical interventions.

18F-fluoride uptake in bone metastasis: morphologic and metabolic analysis on integrated PET/CT

The aim of our study was to evaluate detectability of bone metastatic lesions and evaluate the correlation between (18)F-fluoride uptake patterns on positron emission tomography (PET) and morphologic changes on CT using integrated PET/CT. We performed whole-body (18)F-fluoride PET/CT staging for 27 patients with known cancer. Tumor types comprised breast (n = 7), prostate (n = 7), and others (n = 13). A total of 154 uptake lesions were evaluated. Both tracer uptake patterns determined by (18)F-fluoride PET and morphologic patterns based on CT findings such as morphologic changes, involved locations, and grades scored using five-point scale were compared with histologic tumor subtypes and clinical laboratory data. CT patterns of metastatic lesion were lytic or unclassified in 26 lesions, sclerotic in 53 lesions, and mixed in 75 lesions. Multiple linear regression analysis revealed that metastatic bone lesions with high maximum standardized uptake value (SUVmax) tended to show sclerotic or mixed changes on CT (P < 0.0001), and were also distributed in bone cortex alone or both bone cortex and medulla (P < 0.0001). In patients with bone metastasis, the lesions with sclerotic or mixed changes or located in bone cortex alone or both bone cortex and medulla tend to show high SUVmax on (18)F-fluoride PET/CT.

Osteocutaneous Free Flap Including Medial and Lateral Scapular Crests: Technical Aspects, Viability, and Donor Site Morbidity

The aims of the present study were to check for metabolism of the bony segments of osteocutaneous free flaps that included lateral as well as medial scapular crests by 18F-fluoride positron emission tomography (PET)/computed tomography (CT) examinations and to assess donor site morbidity. Twenty patients were included in the study. In 10 patients, osteocutaneous free flaps were harvested that included lateral as well as medial scapular crests. Seven days after surgery, an 18F-fluoride PET/CT examination was performed to assess the metabolism and viability of the bony segments. In the additional 10 patients, flaps were harvested that only included the lateral scapular crest. All patients were asked to fill in the disabilities of the arm, shoulder, and hand (DASH) questionnaire 1 and 6 months after surgery. In the 10 free flaps that included lateral as well as medial scapular crests, 18F-fluoride PET/CT examinations revealed metabolism and viability of both bony segments. The DASH scores for the two patient groups did not differ significantly at 1 and 6 months after surgery (p(1 month) = 0.520, p(6 months) = 0.545). It seems that scapular osteocutaneous free flaps adopting lateral as well as medial scapular crests are a viable option for mandibular reconstruction and may be an alternative to the fibular double barrel.

Differences in regional bone perfusion and turnover between lumbar spine and distal humerus: 18F-fluoride PET study of treatment-naïve and treated postmenopausal women

The functional imaging technique of 18F-fluoride positron emission tomography ( 18F-PET) allows the non-invasive assessment of regional bone blood perfusion and turnover. Bone perfusion and turnover measured using 18F-PET correlate closely with those obtained experimentally and so they can be readily applied in clinical research studies. The aim of this study was to compare bone perfusion and turnover between the lumbar spine and humerus in both treatment naïve postmenopausal women ( n = 11) and those on stable antiresorptive therapy ( n = 12). All women had a BMD T-score of less than − 2 at the spine and/or hip. Each woman had a dynamic PET scan of the lumbar spine and distal humerus after injection of 90 MBq 18F-fluoride. Using a three-compartmental model bone perfusion ( K 1), the net plasma clearance of tracer to bone mineral ( K i) reflecting regional bone turnover and the rate constants k 2– k 4 describing the transport of fluoride between plasma, an extravascular bone compartment and bone mineral compartment were calculated. Mean bone perfusion ( K 1) and bone turnover ( K i) were significantly higher at the lumbar spine compared to the humerus for both treatment-naïve and antiresorptive groups. K 1 values were on average 3 times greater while K i was approximately 50% greater at the lumbar spine. The rate constant k 2, the reverse transport of fluoride from the extravascular compartment to plasma, was significantly lower at the humerus compared to the lumbar spine in both groups. The ratio K i/ K 1 describing the unidirectional extraction efficiency to bone mineral was significantly greater at the humerus compared to the lumbar spine for both study groups. No significant differences between skeletal sites were observed for k 3 or k 4. In conclusion a significant skeletal heterogeneity was observed in terms of bone perfusion and turnover between the lumbar spine and humerus. 18F-PET may aid in our understanding of the importance of bone perfusion in osteoporosis and differences in regional bone turnover with disease and in response to therapy.

Analysis of bone mineral density and bone turnover in the presence of polymethylmethacrylate particles

Polymethylmethacrylate (PMMA) particles generated from joint arthroplasties appear to contribute to aseptic implant loosening through inflammation-induced periprosthetic osteolysis. However, osteolysis appears to be multifactorial; whether a direct link exists between PMMA particles and osteolysis in vivo is unproven. With the aim to define the relationship between PMMA particles and osteolysis, the authors analyzed the bone mineral density, using microCT scans preoperatively, the first day postoperatively and then every 7-10 days for 32 days, and bone turnover, using (18)F-fluoride positron emission tomography scanner (PET scan) at 8 weeks in four groups of mice that had undergone intramedullary femoral injection. The experimental group of five mice was injected with PMMA particles, and compared with two negative control groups (no injection and injection with the carrier, phosphate-buffered saline) and one positive control group (injection of PMMA particles contaminated with endotoxin). There was no significant change in bone mineral density with addition of PMMA particles, and no evidence of osteolysis. However, bone turnover was increased in the presence of PMMA particles. Even though a direct link between PMMA particles and osteolysis was not found in the short term, PMMA particles appear to influence the regenerative capacity of bone.

Evaluation of lesion in a spontaneous osteonecrosis of the knee using 18F-fluoride positron emission tomography

Positron-emission tomography (PET) imaging has several advantages over conventional scintigraphy, including a high spatial resolution and the ability to quantify disease progression. Recently, (18)F-fluoride PET has been applied to the evaluation of malignant tumors and musculoskeletal disorders. In our current study, spontaneous osteonecrosis of the knee (SONK) was visualized using this technique. We determined whether PET images can reveal SONK lesions, whether there were significant differences in the maximum standardized uptake value (SUVmax) among each of the SONK stages, and finally if there was any correlation between the maximum SUVmax value and size of the SONK lesion measured both by radiography and MRI. Fourteen knees from 13 patients diagnosed with SONK were imaged using a PET scanner. In all cases, PET showed an accumulation of 18F-fluoride in the medial condyle. The SUVmax ranged from 8.6 to 23.7 with an average of 15.1 +/- 3.7 and was measured at different disease stages with an average of 12.4 +/- 5.9 in Stage 2 (n = 5), 16.3 +/- 1.4 in Stage 3 (n = 4), and 16.8 +/- 4.3 (n = 5) in Stage 4 lesions. There were no significant differences in these measurements between the SONK stages. However, a significant positive correlation between the SUVmax and lesion size, including the surface area of the lesion (r2 = 0.692, P = 0.0002) and the condyle width ratio (r2 = 0.365, P = 0.022), was found. The approximate volumes of the lesions measured by MRI had an average of 4.8 +/- 3.1 cm3, and also showed a significant correlation with the SUVmax (r2 = 0.853, P < 0.0001). Hence, our present results indicate that a high SUV is indicative of a large SONK lesion.

Detection of bone metastases in patients with prostate cancer by 18F fluorocholine and 18F fluoride PET–CT: a comparative study

The aim of this prospective study was to compare the potential value of (18)F fluorocholine (FCH) and (18)F fluoride positron emission tomography (PET)-CT scanning for the detection of bony metastases from prostate cancer. Thirty-eight men (mean age, 69+/-8 years) with biopsy-proven prostate cancer underwent both imaging modalities within a maximum interval of 2 weeks. Seventeen patients were evaluated preoperatively, and 21 patients were referred for post-operative evaluation of suspected recurrence or progression based on clinical algorithms. The number, sites and morphological patterns of bone lesions on (18)F FCH and (18)F fluoride PET-CT were correlated: Concordant lesions between the two modalities with corresponding changes on CT were considered to be positive for malignancy; discordant lesions were verified by follow-up examinations. The mean follow-up interval was 9.1 months. Overall, 321 lesions were evaluated in this study. In a lesion-based analysis, a relatively close agreement was found between these two imaging modalities for detection of malignant bone lesions (kappa=0.57), as well as in a patient-based analysis (kappa=0.76). Sixteen malignant sclerotic lesions with a high density were negative in both (18)F FCH and (18)F fluoride PET-CT [mean Hounsfield unit (HU), 1,148+/-364]. There was also a significant correlation between tracer intensity by SUV and density of sclerotic lesions by HU both in (18)F FCH PET-CT (r= -0.28, p < 0.006) and (18)F fluoride PET-CT (r= -0.20, p<0.05). The sensitivity, specificity and accuracy of PET-CT in the detection of bone metastases in prostate cancer was 81%, 93% and 86% for (18)F fluoride, and 74% (p=0.12), 99% (p=0.01) and 85% for FCH, respectively. (18)F FCH PET-CT led to a change in the management in two out of 38 patients due to the early detection of bone marrow metastases. (18)F fluoride PET-CT identified more lesions in some patients when compared with (18)F FCH PET-CT but did not change patient management. FCH PET-CT may be superior for the early detection (i.e. bone marrow involvement) of metastatic bone disease. In patients with FCH-negative suspicious sclerotic lesions, a second bone-seeking agent (e.g. (18)F fluoride) is recommended. (18)F fluoride PET-CT demonstrated a higher sensitivity than (18)F FCH PET-CT, but the difference was not statistically significant. Furthermore, (18)F fluoride PET could be also negative in highly dense sclerotic lesions, which presumably reflects the effect of treatment. It will be important to clarify in future studies whether these lesions are clinically relevant when compared with metabolically active bone metastases.

Recent developments in urologic oncology: positron emission tomography molecular imaging

Traditional morphologically based imaging modalities in uro-oncology are now being complemented by the functional and molecular imaging technique positron emission tomography (PET). This review highlights the most important recent developments. Prostate cancer: PET imaging with the new radiotracers 11C-choline, 18F-fluorocholine, and 11C-acetate show promising results. The role of anti-1-amino-3-18F-fluorocyclobutane-1-carboxylic acid remains to be elucidated further. 18F-fluoride PET is useful for the detection of bone metastases. Bladder cancer: 18F-fluorodeoxyglucose (FDG) PET/CT with delayed images after a diuretic and oral hydration may improve detection of locally recurrent or residual bladder tumours. Both 18F-FDG PET and 11C-choline PET may be useful for staging of bladder cancer. Renal cancer: 18F-FDG PET has a role in staging and restaging of the disease. Recently, 124I-cG250 PET has shown promising results in the detection of clear-cell renal carcinoma. Testicular cancer: 18F-FDG PET is useful in staging and follow-up after treatment. There are no important recent developments with new radiopharmaceuticals in testicular cancer. The utility of PET molecular imaging in uro-oncology expanded due to the new metabolic PET tracers with more favourable properties.

On the Horizon From the ORS

On the Horizon From the ORS

The use of 18F-fluoride and 18F-FDG PET scans to assess fracture healing in a rat femur model

Currently available diagnostic techniques can be unreliable in the diagnosis of delayed fracture healing in certain clinical situations, which can lead to increased complication rates and costs to the health care system. This study sought to determine the utility of positron emission tomography (PET) scanning with (18)F-fluoride ion, which localizes in regions of high osteoblastic activity, and (18)F-fluorodeoxyglucose (FDG), an indicator of cellular glucose metabolism, in assessing bone healing in a rat femur fracture model. Fractures were created in the femurs of immunocompetent rats. Animals in group I had a fracture produced via a manual three-point bending technique. Group II animals underwent a femoral osteotomy with placement of a 2-mm silastic spacer at the fracture site. Fracture healing was assessed with plain radiographs, (18)F-fluoride, and (18)F-FDG PET scans at 1, 2, 3, and 4-week time points after surgery. Femoral specimens were harvested for histologic analysis and manual testing of torsional and bending strength 4 weeks after surgery. All fractures in group I revealed abundant callus formation and bone healing, while none of the nonunion femurs were healed via assessment with manual palpation, radiographic, and histologic evaluation at the 4-week time point. (18)F-fluoride PET images of group I femurs at successive 1-week intervals revealed progressively increased signal uptake at the union site during fracture repair. In contrast, minimal tracer uptake was seen at the fracture sites in group II at all time points after surgery. Data analysis revealed statistically significant differences in mean signal intensity between groups I and II at each weekly interval. No significant differences between the two groups were seen using (18)F-FDG PET imaging at any time point. This study suggests that (18)F-fluoride PET imaging, which is an indicator of osteoblastic activity in vivo, can identify fracture nonunions at an early time point and may have a role in the assessment of longitudinal fracture healing. PET scans using (18)F-FDG were not helpful in differentiating metabolic activity between successful and delayed bone healing.

Clinical evaluation of the effect of attenuation correction technique on18F-fluoride PET images

The purpose of this study is to evaluate effect of attenuation correction technique on 18F-fluoride positron emission tomography (PET). We performed PET scans after the injection of 185 MBq 18F-fluoride on 32 patients from October 20th, 2004 to April 13th, 2005. We calculated bone-to-muscle ratios for the images with and without attenuation correction. We placed regions of interest (ROIs) on normal bone accumulation in 22 patients. The exclusion criteria were bone metastasis, Paget's disease, and rheumatoid arthritis. Several regions were chosen for ROI placement: skull, cervical vertebra, mandible, scapula, thoracic vertebra, rib, humerus, lumbar vertebra, radius, ulna, pelvis, femoral head, femoral shaft, tibia, and fibula. The count ratios of normal bones to gluteus muscle were calculated as bone-to-muscle ratios. The count ratios of abnormal skeletal lesions to gluteus muscles were calculated as bone-to-muscle ratios, while the count ratios of abnormal skeletal lesions to normal bones were calculated as bone-to-bone ratios. PET images without attenuation correction showed significantly higher mean bone-to-muscle ratios than those with attenuation correction (p < 0.05) for all normal bones except the femoral head and lumbar vertebrae. For abnormal bones, bone-to-muscle ratios without attenuation correction were significantly higher than those with attenuation correction (p < 0.005). The same statistical significance was found for bone-to-bone ratios (p < 0.005). The attenuation correction technique is not necessary to conduct the visual interpretation of 18F-fluoride PET images. The bone-to-muscle ratio analysis without attenuation correction may be of use to differentiate malignant from benign disease processes.

Back Pain in Adolescents

The aim of the present study was to assess the ability of a novel bone imaging technique to diagnose accurately the cause for back pain as an isolated and presenting complaint in adolescents. An integrated 18F-fluoride positron-emission tomography-computed tomography (PET-CT) study was performed at the same setting without changing the patients' position, followed by generation of fused images of functional and anatomical data. Fifteen subjects were included in the study. The interpretation of PET-CT fused images was based on increased 18F-fluoride uptake and the corresponding CT-located abnormality. Ten patients had positive findings that included 4 cases of spondylolysis (3 of them active), 3 frank fractures (2 of the transverse process and 1 of the facet), 2 osteoid osteomas, 1 osteitis pubis, 1 sacroiliitis, and 2 herniated disks. Three patients presented 2 coexisting pathologies. Treatment was tailored based on final diagnosis. In 5 patients, in whom no abnormality was identified, the back pain resolved spontaneously. The 18F-fluoride PET-CT can detect spinal lesions with high diagnostic accuracy in adolescents with back pain. Considering the associated costs and radiation exposure, it should be used at present only in cases of long-standing and disabling back pain in which other imaging modalities were inconclusive.

The Relationship Between Regional Bone Turnover Measured Using 18F-fluoride Positron Emission Tomography and Changes in BMD Is Equivalent to That Seen for Biochemical Markers of Bone Turnover

Bone turnover is an important determinant of fracture risk. 18F-fluoride positron emission tomography ( 18F-PET) allows the direct assessment of bone turnover at the clinically important skeletal sites such as the lumbar spine. The aim of this study was to determine if the relationship between regional bone turnover measured using 18F-PET and changes in bone mineral density (BMD) is equivalent to that seen for global skeletal measurements of biochemical markers of bone turnover. Forty-three women who had previously had an 18F-PET scan at the lumbar spine, assessment of biochemical markers of bone turnover, and a dual-energy X-ray absorptiometry scan of BMD at the lumbar spine and hip (baseline assessments) were split into 1 of 2 groups: (1) 22 women who commenced treatment for osteoporosis within 2 mo of having the baseline assessments (Treatment group); (2) 21 women who had not taken any treatments for osteoporosis since having the baseline assessments (Untreated group). Sixteen of the women in the Treatment group started risedronate therapy as part of a prospective study they were participating in, whereas the decision to treat the remaining 6 women was made by the subject's treating physician. Subjects had between 2 and 5 BMD scans over a median follow-up time of 4.1 yr to estimate the annual percentage change in BMD since baseline. The relationship between the tertiles of 18F-PET skeletal kinetic parameter K i , reflecting regional bone turnover, and annual changes in lumbar spine and hip BMD were compared to that seen for bone formation (bone-specific alkaline phosphatase, BSALP) and bone resorption (urinary deoxypyridinoline) markers. Treated women in the highest tertile of both regional ( 18F-PET) and global (biochemical markers) bone turnover showed the greatest annual percentage increases in lumbar spine BMD. The annual increase in lumbar spine BMD was 1.8%, 2.2%, and 3.2% for women in the lowest, middle, and highest tertile of BSALP, respectively, which was similar to that obtained for the regional measurement of K i of 1.7%, 2.2%, and 2.7% respectively. Untreated women in the highest tertile of regional and global bone turnover had larger decreases in lumbar spine BMD compared to those women in the lowest tertile, with a 1.4- to 4.8-fold difference in the annual decrease in BMD between the two. Less consistent patterns were observed when assessing the relationship between regional and global bone turnover with changes in hip BMD. This study has demonstrated that the relationship between regional bone turnover measured directly at the lumbar spine with changes in BMD is similar to that seen for global skeletal bone turnover using biochemical markers.