Alteration of Volumetric Bone Mineral Density Parameters in Men with Spinal Cord Injury.

Spinal cord injury (SCI) induces severe losses of trabecular and cortical volumetric bone mineral density (vBMD), which cannot be discriminated with conventional dual-energy X-ray absorptiometry (DXA) analysis. The objectives were to: (i) determine the effects of SCI on areal BMD (aBMD) and vBMD determined by advanced 3D-DXA-based methods at various femoral regions and (ii) model the profiles of 3D-DXA-derived parameters with the time since injury. Eighty adult males with SCI and 25 age-matched able-bodied (AB) controls were enrolled in this study. Trabecular and cortical vBMD, cortical thickness and derived strength parameters were assessed by 3D-SHAPER® software at various femoral subregions. Individuals with SCI had significantly lower integral vBMD, trabecular vBMD, cortical vBMD, cortical thickness and derived bone strength parameters (p < 0.001 for all) in total proximal femur compared with AB controls. These alterations were approximately to the same degree for all three femoral subregions, and the difference between the two groups tended to be greater for cortical vBMD than trabecular vBMD. There were minor differences according to the lesion level (paraplegics vs tetraplegics) for all 3D-DXA-derived parameters. For total proximal femur, the decreasing bone parameters tended to reach a new steady state after 5.1 years for integral vBMD, 7.4 years for trabecular vBMD and 9.2 years for cortical vBMD following SCI. At proximal femur, lower vBMD (integral, cortical and trabecular) and cortical thickness resulted in low estimated bone strength in individuals with SCI. It remains to be demonstrated whether these new parameters are more closely associated with fragility fracture than aBMD.

Association between brain metabolism and clinical course of motor functional neurological disorders.

Features of resting brain metabolism in motor functional neurological disorder are poorly characterized. This study aimed to investigate the alterations of resting brain metabolism in a cohort of patients experiencing a first episode of motor functional neurological disorder with recent symptom onset and their association with persistent disability after 3 months. Patients eligible for inclusion were diagnosed with first episode of motor functional neurological disorder, were free from bipolar disorder, substance use disorder, schizophrenia, psychogenic non-epileptic seizure or any chronic or acute organic neurological disorder. Exclusion criteria included current suicidal ideation, antipsychotic intake and previous history of functional neurological disorder. Nineteen patients were recruited in Psychiatry and Neurology departments from two hospitals. Resting brain metabolism measured with 18F-fluorodeoxyglucose positron emission computed tomography at baseline and 3 months was compared to 23 controls without neurological impairment. Disability was scored using Expanded Disability Status Scale and National Institutes of Health Stroke Scale score at baseline and 3 months. Correlations were calculated with Spearman correlation coefficient. Hypometabolism was found at baseline in bilateral frontal regions in patients versus controls, disappearing by 3 months. The patients with Expanded Disability Status Scale score improvement showed greater resting state activity of prefrontal dorsolateral cortex, right orbito-frontal cortex and bilateral frontopolar metabolism at 3 months versus other patients. The resting state metabolism of the right subgenual anterior cingular cortex at baseline was negatively correlated with improvement of motor disability (measured with Expanded Disability Status Scale) between inclusion and 3 months (r = -0.75, P = 0.0018) and with change in motor symptoms assessed with the National Institutes of Health Stroke Scale (r = -0.81, P = 0.0005). The resting state metabolism of the left subgenual anterior cingular cortex at baseline was negatively correlated with improvement in Expanded Disability Status Scale and National Institutes of Health Stroke Scale scores between inclusion and 3 months (r = -0.65, P = 0.01 and r = -0.75, P = 0.0021, respectively). The negative association between the brain metabolism of the right subgenual anterior cingular cortex at baseline and change in National Institutes of Health Stroke Scale score remained significant (r = -0.81, P = 0.0414) after correction for multiple comparisons. Our findings suggest the existence of metabolic 'state markers' associated with motor disability and that brain markers are associated with motor recovery in functional neurological disorder patients.

Cross-Calibration Study of The Stratos And Hologic QDR 4500A Dual-Energy X-Ray Absorptiometers to Assess Bone Mineral Density And Body Composition.

The objective of the study was to assess the agreement between the Stratos (DMS) and QDR 4500A (Hologic) DXAs in determining whole body and regional aBMD, as well as whole body composition. Fifty-five individuals (46 women: 84%) with a mean age of 41 ± 13.0 years (range: 20 to 64) and a mean BMI of 31.9 ± 10 kg/m² (range: 12.2 to 49.5) were consecutively scanned on the same day using the two devices. Predictive equations for areal bone mineral density (aBMD) and whole body composition (WBC) were derived from linear regression of the data. The two DXAs were highly correlated (p<0.001 for all parameters) with a correlation coefficient (r) ranging from 0.89 to 0.99 for aBMD (r=0.89 for whole body, r=0.92 for radius, r=0.95 for femoral neck, r=0.96 for total hip, and r=0.99 for L1-L4). For WBC, the r value was 0.98 for lean tissue mass (LTM) and 1.0 for fat mass (FM). Paired t-tests indicated a statistically significant bias between the two DXAs for the majority of measurements, requiring the determination of specific cross-calibration equations. Compared to QDR 4500A, Stratos underestimated whole body aBMD and LTM and overestimated neck and hip aBMD and whole body FM. Conversely, no significant bias was demonstrated for mean aBMD at L1-L4 and radius. For whole body aBMD and FM, the concordance between the two DXAs was influenced by BMI. Despite a high concordance between the two DXAs, the systematic bias for aBMD and WBC measurements illustrates the need to define cross-calibration equations to compare data across systems.

Comparison of the Lunar Prodigy and Stratos DR Dual-Energy X-Ray Absorptiometers to Assess Regional Bone Mineral Density.

PURPOSE: The first objective of the study was to assess the agreement between the Stratos DR (DMS) and the GE Prodigy (GE) DXAs in determining femoral neck, total hip and lumbar spine aBMD. The second objective was to assess the potential impact of leg positioning (hip flexed at 90° or not) on lumbar spine aBMD. METHODS: Forty-six individuals (n=42 women, 91.3%), with a mean age of 59.7 ± 13 years and mean BMI of 23.8 ± 4.7 kg/m², were scanned consecutively on the same day using the two devices. In a subgroup (n=30), two consecutive Stratos DR scans (with hip flexed at 90° or not) at the lumbar spine were conducted. Predictive equations for hip and lumbar spine aBMD were derived from linear regression of the data. RESULTS: Correlation coefficients for aBMD measured with the two DXAs were characterised by an R² of 0.76 for the femoral neck, 0.89 for the total hip, and 0.86 for the lumbar spine. However, the derived equations for aBMD determination showed an intercept significantly different from 0 for hip aBMD, and a slope significantly different from 1 for lumbar spine aBMD. These results highlight a bias between the two measurements, thus requiring the determination of specific cross-calibration equations for hip and lumbar spine, femoral neck excepted. When compared with values on the Prodigy, mean aBMD on the Stratos DR was higher at the femoral neck (+4.8%, p<0.001) and total hip (+9.6%, p<0.001) and lower at L2-L4 (-8.8%, p<0.001). The coefficient of variation (CV%) for the two consecutive measures at lumbar spine (with different positioning) with the Stratos DR was 2.9%. CONCLUSIONS: The difference in aBMD measured with the two DXAs illustrates the need to define cross-calibration equations when comparing data across systems in order to avoid erroneous conclusions.

In myotonic dystrophy type 1 reduced FDG-uptake on FDG-PET is most severe in Brodmann area 8.

BACKGROUND: In myotonic dystrophy type 1 (DM1), only one FDG-PET study used statistical parametric mapping (SPM) showing frontal reduced FDG-uptake. Our aim was to 1) identify the FDG-PET area with the most severe reduced FDG-uptake using SPM8 in a larger group of patients 2) assess potential correlation between CTG-numbers and FDG-PET. METHODS: FDG-PET was performed in 24 patients and compared to 24 controls. Pearson's correlation was used to analyse correlation. RESULTS: SPM8 revealed Brodmann area 8 as the area with the most severe reduced FDG-uptake. Weak, although not statistically significant, correlation was observed between CTG-numbers and reduced FDG-uptake in Brodmann area 8. CONCLUSION: In DM1, Brodmann area 8 is the area with the most severe reduced FDG-uptake on FDG-PET. Brodmann area 8 reduced FDG-uptake is correlated -although weakly- to CTG-repeat numbers.

Comparison of the Discovery A and Stratos DR densitometers for assessing whole-body and regional bone mineral density and body composition.

PURPOSE: The agreement between the Stratos DR and Discovery A densitometers was assessed for measurements of whole-body (WB) and regional fat mass (FM), fat-free soft tissue (FFST) and bone mineral density (BMD). Moreover, the precision of the Stratos DR was also evaluated. METHODS: Fifty participants (35 women, 70%) were measured consecutively, once on the Discovery A and once on the Stratos DR. In a subgroup of participants (n = 29), two successive measurements with the Stratos DR were also performed. RESULTS: FM, FFST and BMD measured with the two devices were highly correlated, with a coefficient of correlation ranging from 0.80 to 0.99. Bland-Altman analyses indicated significant bias between the two devices for all measurements. Thus, compared to the Discovery A, the Stratos DR underestimated WB BMD and WB and regional FM and FFST, with the exception of trunk FM and visceral adipose tissue (VAT), which were overestimated. Precision error for the Stratos DR, when expressed as root mean square-coefficient of variation (RMS-CV%) for FM, was 1.4% for WB, 3.0% for the gynoid and android regions, and 15.9% for VAT. The RMS-CV% for FFST was 1.0% for WB. The root mean square of standard deviation for WB BMD was 0.018 g/cm², corresponding to a 1.4% CV. The least significant change was 0.050 g/cm² (SD), and 4.0% was considered to be a significant biological change. CONCLUSIONS: Differences between the Stratos DR and Discovery A measurements are significant and require the use of translational cross-calibration equations. For most of the BMD and body composition parameters, our results demonstrated good Stratos DR precision.

A Recanalized Umbilical Vein Hypermetabolic Thrombosis Mimicked an Hepatocellular Carcinoma Recurrence: A New Pitfall?

ABSTRACT: A transarterial left hepatic artery radioembolization involving 90Y microspheres was performed on a cirrhotic man with hypermetabolic 18F-FDG segment III hepatocellular carcinoma. During the 18F-FDG PET/CT follow-up, the disappearance of the hypermetabolic lesion was initially observed. Then, a focal segment III hypermetabolism reappeared mimicking a recurrence before disappearing without any treatment. Finally, the hepatic MRI demonstrated that the transitory segment III hypermetabolism matched a thrombus of the dilated recanalized umbilical vein.

Definition of an adapted cut-off for determining low lean tissue mass in older women with obesity: a comparison to current cut-offs.

The prevalence of sarcopenia in patients with obesity varies according to the definition used. The purpose of our study was to: (i) determine the prevalence of sarcopenia in terms of lean tissue mass in older women with obesity using the current cut-offs, (ii) redefine a specific cut-off for low lean tissue mass (LLTM), and (iii) re-determine the prevalence of LLTM using this new cut-off. Appendicular lean mass (ALM) and the ALM index [ALM/height2: ALMI(h2)] and ALMI/body mass index [ALMI(BMI)] were determined in 791 women with or without obesity. LLMM prevalence was calculated using the current cut-offs: EWGSOP2: ALM < 15 kg and ALMI(h2) < 5.5 kg/m2; FNIH: ALM < 15.02 kg and ALMI(BMI) < 0.51; and IWGS: ALMI(h2) < 5.67 kg/m2 and cut-offs newly determined from data provided from young women with obesity. ALM, ALMI(h2) and ALMI(BMI) were lower in older compared to young obese women. Using the current cut-offs, a wide distribution of LLTM prevalence (0 to 29.2%) was observed. When the newly determined cut-offs were applied - i.e., ALM < 18.51 kg; ALMI(h2) < 7.15 kg/m2, ALMI(BMI) < 0.483, and T-score: [(ALMI(h2) measured)-(2.08 + 0.183*BMI)]/0.72] - the LLTM mass prevalence was 17.37%; 8.47, 14.8 and 12.71%. respectively. This study showed that the current cut-offs for LLTM as criteria for sarcopenia diagnosis are not adapted to the obese population. Although the new "static" cut-offs appeared to be more adapted, a "dynamic" cut-off for ALMI(h2) that took into account the BMI and thus the obesity severity appeared even more relevant.

Diagnostic Performance of Cervical Ultrasound, 99mTc-Sestamibi Scintigraphy, and Contrast-Enhanced 18F-Fluorocholine PET in Primary Hyperparathyroidism.

Preoperative localization of pathologic parathyroids is crucial for minimally invasive treatment of primary hyperparathyroidism (PHPT). This study compared contrast-enhanced 18F-fluorocholine PET/CT, cervical ultrasonography (CU), and conventional scintigraphic imaging modalities (MIBI scintigraphy, consisting of 99mTc-sestamibi/123I-sodium iodide SPECT/CT, 99mTc-sestamibi/123I-sodium iodide planar subtraction imaging, and 99mTc-sestamibi planar dual-phase imaging), combined and individually, for preoperative localization of hyperfunctional parathyroids in PHPT. The gold standard was histologic examination. Methods: Data from consecutive patients with clinically suspected PHPT were retrospectively collected. All 3 imaging modalities were systematically performed. The ability of 18F-fluorocholine PET/CT, CU, and MIBI scintigraphy to identify a hyperfunctional parathyroid and specify the side or identify an ectopic location was noted. Patients underwent surgical exploration if at least 1 examination was positive. The findings of CU + MIBI scintigraphy combined were considered positive if CU and MIBI scintigraphy separately showed a hyperfunctional parathyroid gland on the same side or in the same ectopic location; any findings other than these were considered negative. The composite judgment criterion for pathologic parathyroid was a combination of histologic analysis and normalization of parathyroid hormone and calcium levels. Results: In total, 149 pathologic parathyroids were found in 143 of the 144 included patients. 18F-fluorocholine PET/CT diagnosed 148 of 149 pathologic parathyroids. Only 4 false-positives and 1 false-negative were found. The 18F-fluorocholine PET/CT sensitivity of 99.3% was superior to that of CU, at 75.2% (P < 0.0001); MIBI scintigraphy, at 65.1% (P < 0.0001); and CU + MIBI scintigraphy, at 89.9%, (P = 0.0009). Five of the 5 ectopic locations were diagnosed by 18F-fluorocholine PET/CT, 2 of the 5 by MIBI scintigraphy, and none by CU. Accuracy was better for 18F-fluorocholine PET/CT, at 98%, than for CU, at 84% (P < 0.0001); MIBI scintigraphy, at 81% (P < 0.0001); or CU + MIBI scintigraphy, at 91% (P < 0.0001). Among the 72 (50%) patients who had a negative CU + MIBI scintigraphy result, 18F-fluorocholine PET/CT correctly identified hyperfunctional thyroids in 70 (97.2%). Average uptake in the 18F-fluorocholine PET/CT hyperfunctional parathyroid was higher than that in the adjacent thyroid (SUVmax adjusted for lean body mass, 6.45 vs. 2.15) (P < 0.0001). Conclusion: The accuracy of 18F-fluorocholine PET/CT is higher than that of CU and MIBI scintigraphy for localization of hyperfunctional parathyroids, justifying the systematic use of 18F-fluorocholine PET/CT as the first-line method for PHPT diagnosis.

In patients with anorexia nervosa, myokine levels are altered but are not associated with bone mineral density loss and bone turnover alteration.

Objectives: The two-fold aim of this study was: (i) to determine the effects of undernutrition on the myokines in patients with restrictive anorexia nervosa (AN) and (ii) to examine the potential link between myokines and bone parameters. Methods: In this study, 42 young women with restrictive AN and 42 age-matched controls (CON) (mean age, 18.5 ± 4.2 years and 18.6 ± 4.2 years, respectively) were enrolled. aBMD and body composition were determined with DXA. Resting energy expenditure (REEm), a marker of energy status, was indirectly assessed by calorimetry. Bone turnover markers and myokines (follistatin, myostatin and irisin) were concomitantly evaluated. Results: AN patients presented low aBMD at all bone sites. REEm, bone formation markers, myostatin and IGF-1 were significantly lower, whereas the bone resorption marker and follistatin were higher in AN compared with controls. No difference was observed between groups for irisin levels. When the whole population was studied, among myokines, only myostatin was positively correlated with aBMD at all bone sites. However, multiple regression analyses showed that in the AN group, the independent variables for aBMD were principally amenorrhoea duration, lean tissue mass (LTM) and procollagen type I N-terminal propeptide (PINP). For CON, the independent variables for aBMD were principally LTM, age and PINP. Whatever the group analysed, none of the myokines appeared as explicative independent variables of aBMD. Conclusion: This study demonstrated that despite the altered myokine levels in patients with AN, their direct effect on aBMD loss and bone turnover alteration seems limited in comparison with other well-known disease-related factors such as oestrogen deprivation.

Assessment of the Stratos, a new pencil-beam bone densitometer: dosimetry, precision, and cross calibration.

The goal of this study was to assess a new pencil-beam densitometer, the Stratos (Diagnostic Medical Systems, Pérols, France). Evaluation of the dosimetry and precision were done together with an in vivo cross-calibration study performed with the fan beam densitometer Discovery A (Hologic, Bedford, MA). The results indicated that the Stratos performed bone mineral density (BMD) measurements with a good precision, low radiation dose, and good agreement with the Discovery A. The air dose, measured by an ionization chamber, was 40 µGy. The effective dose was assessed using an anthropomorphic phantom and thermoluminescent detectors resulting in 1.96 and 0.31 µSv for a lumbar spine and proximal femur scan, respectively. The average scattered dose rate at a distance of 1m from the device was 1.06 and 1.21 µSv.h(-1) in the lumbar spine and left proximal femur scan mode, respectively. For the precision evaluation, 30 patients underwent 2 lumbar spine and 2 proximal femur scans with repositioning after each scan. The percentage root-mean-square coefficient of variation was 1.22%, 1.38%, 2.11%, and 0.86% for the lumbar spine (L1-L4), lumbar spine (L2-L4), femoral neck, and total hip, respectively. The cross-calibration studies were done on 57 patients (60 ± 9 yr). Lumbar spine, left neck, and left total hip mean BMD were 3.10% lower and 11.94% and 8.83% higher, respectively, with the Stratos compared with the Discovery A. Cross-calibration equations were calculated with a correlation coefficient of 98% (p<0.01) for the lumbar spine (L2-L4), 94% (p<0.01) for the left neck, and 92% (p<0.01) for the left total hip. After standardizing the Stratos measures using the cross-calibration equations, LIN's concordance correlation coefficient was 0.98, 0.93, and 0.92 for the lumbar spine (L2-L4), left neck, and total hip, respectively.

Modification of bone mineral density, bone geometry and volumetric BMD in young women with obesity.

BACKGROUND: Most obese women with low-trauma fractures present normal areal bone mineral density (aBMD), suggesting that other bone parameters are more determinant for fracture risk in these patients. OBJECTIVES: (i) Determine the effects of obesity in young women on areal bone mineral density (aBMD), bone geometry, strength, and volumetric BMD determined by advanced DXA-based methods; (ii) model the profiles of bone parameters for each population with age; and (iii) determine the factors related to body composition (i.e. lean tissue mass and fat mass) potentially implicated in the "bone adaptation" in the femoral region. SUBJECTS AND METHODS: Two hundred and twenty adolescent and young women from 18 to 35 years old were enrolled in this study: 128 patients with obesity and 92 age-matched (±6 months) normal-weight controls. aBMD was determined with DXA, whereas hip geometry and strength parameters were assessed by hip structural analysis (HSA) and volumetric BMD by 3D-SHAPER® software. RESULTS: Compared with controls, subjects with obesity presented significantly higher aBMD at all bone sites, but the difference was greater at hip compared with lumbar spine or radius. Bone size estimates (i.e. cortical thickness), as well as strength estimates (i.e. cross-sectional area) were higher at all femoral subregions including femoral neck, intertrochanteric region and femoral shaft in young women with obesity. In whole proximal femur and all femoral compartments, vBMD was also higher in subjects with obesity, but the difference between groups was greater for cortical vBMD compared with trabecular vBMD. When hip bone parameters were modelled for each group from individual values, maximal values were reached between 20 and 26 years in both groups but, whatever the age, subjects with obesity presented higher values than controls. In both groups, lean body mass (LBM) was the parameter most positively associated with the greatest number of bone parameters studied. CONCLUSION: Our study confirmed that young women with obesity presented higher aBMD, better hip geometry and greater strength compared with normal-weight controls. Additionally, cortical and trabecular compartments measured by 3D-SHAPER® were favourably and concomitantly modified. However, it remains to be demonstrated whether the evaluation of these new parameters would provide better prediction of fracture risk in this population than aBMD.

The quantitative ultrasound method for assessing low bone mass in women with anorexia nervosa.

This study investigated the potential role of quantitative ultrasound (QUS) to assess low bone mass in anorexia nervosa patients (AN). Bone parameters from QUS and DXA were positively correlated and significantly reduced in AN compared with controls, suggesting that QUS is a pertinent technique to assess low bone mass in these patients. PURPOSE: The aim of this study was to investigate the potential role of an alternative technique, quantitative ultrasound (QUS), to assess low bone mass in patients with anorexia nervosa (AN). METHODS: Two hundred seven young women (134 patients with AN and 73 healthy controls) with ages ranging from 14.4 to 38.4 years participated in this observational cross-sectional study. Bone mass was concomitantly evaluated by DXA to determine areal bone mineral density (aBMD; g/cm2) at hip, lumbar spine, and radius and by QUS to determine broadband ultrasound attenuation (BUA; dB/MHz) at the heel. RESULTS: BUA (66.5 ± 4.6 dB/MHz vs 61.0 ± 5.0 dB/MHz) and aBMD at the hip (0.916 ± 0.013 g/cm2 vs 0.806 ± 0.010 g/cm2), lumbar spine (0.966 ± 0.012 g/cm2 vs 0.886 ± 0.010 g/cm2), and radius (0.545 ± 0.005 g/cm2 vs 0.526 ± 0.04 g/cm2) were significantly decreased (p < 0.01) in patients with AN compared with controls. When patient and control data were pooled, BUA was significantly correlated with aBMD at the hip (r = 0.60, p < 0.001), lumbar spine (r = 0.48, p < 0.001), and radius (r = 0.40, p<0.001). In patients with AN, BUA and aBMD were mainly and positively correlated with weight, lean tissue mass, body mass index (BMI), and minimal BMI life and negatively with the duration of both disease and amenorrhea. Better concordance between the two techniques was obtained when absolute BUA and aBMD values were used according to the WHO T score classification. CONCLUSION: BUA measurement at the heel by QUS appears to be a pertinent nonionizing technique to assess low bone mass in patients with AN.

Data acquisition analysis for femoral morphometric X-ray absorptiometry.

Bone mineral density (BMD) is a contributing factor of hip fracture risk. Other factors, such as lifestyle, the propensity for falls, and femoral geometry may influence the risk of hip fracture. The DMS Lexxos densitometer, a dual-energy X-ray densitometer can produce either a single-energy X-ray or a BMD image. The purpose of this study was to evaluate which of these 2 images enables the best detection to make femoral morphometry measurements. Spatial resolution, contrast, and noise were evaluated separately. A contrast-detail phantom was also used for the purpose of overall visual analysis. The spatial resolution was the same in the 2 images. The contrast was better with the BMD image, but the noise was higher. Using the contrast-detail phantom, the single-energy X-ray image allowed globally a better detection of the objects, but results were in the same range with high contrast values. Hip volunteers' morphometric measurements and the Singh Index were evaluated 3 times for each image by 3 observers, and the intra-, inter-, and global reproducibility was computed. The reproducibility of the measurements seems to be better with the single-energy X-ray image but results were not statistically significantly different. These results suggest that even if the image-quality indices were different, the single-energy X-ray image and BMD image are closely useful for clinical morphometric femoral evaluation.

The effect of excessive fat tissue on the measure of bone mineral density by dual X-ray absorptiometry: the impact of substantial weight loss following sleeve gastrectomy.

PURPOSE: Dual-energy X-ray absorptiometry (DXA) is used in clinical routine to determine areal bone mineral density (aBMD). However, it is not clear whether excessive fat mass or substantial weight loss modify the aBMD measurements. The aim of this study was to evaluate the effect of soft tissue composition on aBMD measured by DXA using a clinical model (i.e. sleeve gastrectomy: SG) that induces substantial body weight loss. METHODS: Areal bone mineral density and body composition (fat mass: FM and lean tissue mass: LTM) were determined by DXA in 41 obese patients (33 women, 80.5%) just before SG and 1 month later. RESULTS: One month after SG, mean weight loss was -9.8 ± 2.6 kg, with a significant decrease in LTM and FM (kg) ranging from -7.3% to -9.5%. The relative variation in aBMD was increased at the lumbar spine (2.45 ± 3.44%) and decreased at the hip (-1.47 ± 2.28%), whereas no variation was observed for the whole body and radius. The variation in aBMD at the lumbar spine was inversely correlated with variations in weight, whole-body FM and trunk FM, but not LTM. CONCLUSION: This study shows evidence of a potential effect of body composition, particularly FM, on aBMD. However, given the modest change in aBMD, which was close to the precision error of aBMD measurements, it appears that significant weight loss does not have a clinically significant impact on the evaluation of aBMD using DXA.

Drugs That Modify Cholesterol Metabolism Alter the p38/JNK-Mediated Targeted and Nontargeted Response to Alpha and Auger Radioimmunotherapy.

PURPOSE: For the development of new anticancer therapeutic radiopharmaceuticals, including alpha particle emitters, it is important to determine the contribution of targeted effects in irradiated cells, and also of nontargeted effects in nonirradiated neighboring cells, because they may affect the therapeutic efficacy and contribute to side effects. EXPERIMENTAL DESIGN: Here, we investigated the contribution of nontargeted cytotoxic and genotoxic effects in vitro and in vivo (in xenografted mice) during alpha (212Pb/212Bi, 213Bi) and Auger (125I) radioimmunotherapy (RIT). RESULTS: Between 67% and 94% (alpha RIT) and 8% and 15% (Auger RIT) of cancer cells were killed by targeted effects, whereas 7% to 36% (alpha RIT) and 27% to 29% (Auger RIT) of cells were killed by nontargeted effects. We then demonstrated that the nontargeted cell response to alpha and Auger RIT was partly driven by lipid raft-mediated activation of p38 kinase and JNK. Reactive oxygen species also played a significant role in these nontargeted effects, as demonstrated by NF-κB activation and the inhibitory effects of antioxidant enzymes and radical scavengers. Compared with RIT alone, the use of RIT with ASMase inhibitor (imipramine) or with a lipid raft disruptor (e.g., methyl-beta-cyclodextrin or filipin) led to an increase in clonogenic cell survival in vitro and to larger tumors and less tissue DNA damage in vivo. These results were supported by an inhibitory effect of pravastatin on Auger RIT. CONCLUSIONS: Cell membrane-mediated nontargeted effects play a significant role during Auger and alpha RIT, and drugs that modulate cholesterol level, such as statins, could interfere with RIT efficacy.

Cerebrospinal Fluid, MRI, and Florbetaben-PET in Cerebral Amyloid Angiopathy-Related Inflammation.

BACKGROUND: Cerebral amyloid angiopathy-related inflammation (CAA-ri) is associated with a cerebrospinal fluid (CSF) biomarker profile similar to that observed in CAA. Few CAA-ri patients have been studied by fibrillar amyloid-ß (Aß) imaging (using 11C-Pittsburgh compound B and 18F-florbetapir, but not 18F-florbetaben). OBJECTIVE: To describe CSF biomarkers, magnetic resonance imaging (MRI), and 18F-florbetaben (FBB)-positron emission tomography (PET) changes in CAA-ri patients. METHODS: CSF levels of total tau, phosphorylated tau, Aß1-42, and Aß1-40, MRI (cerebral microbleeds count on susceptibility-weighted imaging and semi-quantitative analysis of fluid-attenuation inversion recovery white matter hyperintensities), and FBB-PET (using both cerebellar cortex and pons to calculate standardized uptake value ratios) were analyzed in nine consecutive CAA-ri patients. RESULTS: A median number of 769 cerebral microbleeds/patient were counted on MRI. When using the pons as reference region, amyloid load on FBB-PET was very strongly correlated to CSF Aß1-40 levels (rho = -0.83, p = 0.008) and moderately correlated to cerebral microbleed numbers in the occipital lobes (rho = 0.59, p = 0.001), while comparisons with other CSF biomarkers were not statistically significant (total tau, rho = -0.63, p = 0.076; phosphorylated tau, rho = -0.68, p = 0.05; Aß1-42, rho = -0.59, p = 0.09). All correlations were weaker, and not statistically significant, when using the cerebellum as reference region. A non-significant correlation (rho = -0.50, p = 0.18) was observed between CSF Aß1-40 levels and cerebral microbleed numbers. CONCLUSION: In CAA-ri, CSF Aß1-40 levels correlated well with amyloid load assessed by FBB-PET when the pons was used as reference, and to a lesser degree with cerebral microbleeds count on MRI. This confirms earlier data on CSF Aß1-40 as an in vivo marker for CAA and CAA-ri.

Radiolabeled Antibodies Against Müllerian-Inhibiting Substance Receptor, Type II: New Tools for a Theranostic Approach in Ovarian Cancer.

We have developed the 16F12 mouse monoclonal antibody (mAb), which targets the Müllerian-inhibiting substance receptor, type II (MISRII), expressed by ovarian tumors. Here, we assessed in preclinical models the possibility of using radiolabeled 16F12 in a theranostic approach for small-volume ovarian peritoneal carcinomatosis, such as after cytoreductive surgery. Methods: DOTA-, DTPA- or deferoxamine mesylate-conjugated 16F12 mAb was radiolabeled with ß-particle (177Lu) or α-particle (213Bi) emitters for therapeutic use and with 89Zr for PET imaging. On the 13th postxenograft day, mice bearing intraperitoneal MISRII-positive AN3CA endometrial carcinoma cell xenografts were treated by conventional intraperitoneal radioimmunotherapy (IP-RIT) with 10 MBq of 177Lu-16F12 or 12.9 MBq of 213Bi-16F12 or by brief intraperitoneal radioimmunotherapy (BIP-RIT) using 50 MBq of 177Lu-16F12 or 37 MBq of 213Bi-16F12. For BIP-RIT, 30 min after injection of the radiolabeled mAbs, the peritoneal cavity was washed to remove the unbound radioactivity. The biodistribution of 177Lu- and 213Bi-16F12 mAbs was determined and then used for dose assessment. Hematologic toxicity was also monitored. Results: The 16F12 mAb was satisfactorily radiolabeled for both therapy and imaging. IP-RIT with 177Lu-16F12 was slightly more efficient in delaying tumor growth than IP-RIT with 213Bi-16F12. Conversely, 213Bi-16F12 was more efficient than 177Lu-16F12 in BIP-RIT. The biodistribution analysis showed that the tumor-to-blood uptake ratio was significantly higher with BIP-RIT than with IP-RIT for both 213Bi- and 177Lu-16F12. Hematologic toxicity was more pronounced with 177Lu-16F12 than with 213Bi-16F12. SPECT/CT images (after BIP-RIT with 177Lu-16F12) and PET/CT images (after injection of 89Zr-16F12 in the tail vein) showed focal uptake at the tumor site. Conclusion: Radiolabeled 16F12 could represent a new theranostic tool for small-volume ovarian peritoneal carcinomatosis. Specifically, 213Bi-16F12-based BIP-RIT could be proposed to selected patients as an alternative adjuvant treatment immediately after cytoreductive surgery. An anti-MISRII mAb is currently being used in a first-in-human study, thus making radiolabeled anti-MISRII mAbs a realistic theranostic option for the clinic.

FDG-PET in Creutzfeldt-Jakob disease: Analysis of clinical-PET correlation.

OBJECTIVE: To assess the relationship between clinical pattern and cerebral glucose metabolism on [18F]fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) in Creutzfeldt-Jakob disease (CJD). METHODS: Predefined clinical signs (ataxia, visual, pyramidal, myoclonus, limb apraxia, limb dystonia, sensory, parkinsonism, and corticobasal syndrome [CBS]) and FDG-PET data were assessed in consecutive CJD patients. Two types of statistical parametric mapping (SPM) analyses, using stringent level of significance p < 0.001 and extent threshold of 100 voxels, were performed: one comparing CJD patients presenting specific sign against CJD patients without this specific sign (inter-CJD analysis), and one comparing CJD patients with specific sign against 18 healthy controls (CJD-control analysis). RESULTS: Fifteen CJD patients (11 probable and two histologically proven sporadic and two genetic CJD) were analyzed. CJD-control analysis of the entire CJD group showed lateralized frontal and parietal hypometabolism. When analyzing clinical CJD subgroups, inter-CJD analyses showed hypometabolism in more restricted areas than on CJD-control analyses. For CJD patients presenting with ataxia, visual signs and CBS (and CBS-associated signs), additional hypometabolic areas probably related to the specific signs were identified: pons and middle cerebellar peduncles in patients with ataxia; occipital cortex in patients with visual signs; and prerolandic and lateral parietal cortex in patients with CBS. For pyramidal signs, sensory loss, and parkinsonism, no abnormalities in brain areas typically involved in these signs were observed. CONCLUSION: In addition to lateralized frontal and parietal hypometabolism previously reported in CJD and observed here, hypometabolism in brain areas related to some specific signs (i.e. ataxia, visual signs, and CBS) is also seen.

18F-Florbetaben: A New Tool for Amyloidosis Staging?

We report the case of a 73-year-old man with a documented (renal biopsy) light-chain amyloidosis (AL) imaged with F-AV-1 (F-florbetaben) compared with a volunteer. A cardiac amyloidosis was suspected. As it was an AL and not a transthyretin amyloidosis, F-FDG and F-florbetaben PET/CT were preferred to bone scan. F-FDG scintigraphy showed a focal cardiac hypermetabolism. In addition of the heart, F-florbetaben scintigraphy showed an intense spleen and thyroid pathologic uptake and a moderate salivary gland and kidney uptake. F-florbetaben PET/CT appears to be useful for staging systemic amyloidosis.