Assessment of regional and total skeletal metabolism using 18F-NaF PET/CT in patients with chronic kidney disease.

OBJECTIVE: The study aims to assess regional and total bone metabolic activity in patients with chronic kidney disease using Na[18F]F PET and correlation between semi-quantitative indices and blood parameters. METHODS: Seventy-two subjects (mean age 61.8 ± 13.8 years) were included. Of these 24/72 patients had end-stage renal disease (ESRD) (GFR < 15 mL/min/1.73 m2), 38/72 had chronic kidney disease (CKD) (GFR between 60 and 15 mL/min/1.73 m2), and 10/72 were controls with normal renal function. All subjects underwent Na[18F]F PET-CT with a dose activity of 0.06 mCi/Kg. Regional and total skeletal metabolism were assessed with mean SUVs in a skeletal volume of interest (VOI), bone to soft tissue index (B/S), global SUV mean (GSUV mean) of the whole bone, and uptake in the femoral neck. RESULTS: Statistically significant differences were observed in a number of 18F-NaF metrics like femoral neck metabolism in CKD and ERSD groups in comparison to control in right (P = 0.003) and left femur (P = 0.006), bone to soft tissue index in the femur (P = 0.016) and GSUV5 (P = 0.006). There is also a significant difference in SUV mean in lumbar vertebrae (L1-L4) among CKD, ESRD, and controls. There was a moderate correlation between 18F-NaF PET scan uptake and blood parameters such as ALP and PTH. Na[18F]F uptake parameters were significantly different in low versus high bone turnover state. CONCLUSIONS: The assessment of total skeleton and regional metabolism and bone turnover in CKD patients is feasible with Na[18F]F PET. Na[18F]F can help to detect early changes in bone metabolism and assess the progression of bone disease in this complex condition. Quantification with Na[18F]F PET might provide better assessment of the bone turnover. The difference in Na[18F]F uptake in CKD compared to controls is likely related to a change in bone turnover which, however, requires further validation.

Cantharidin and sodium fluoride attenuate the negative inotropic effects of carbachol in the isolated human atrium.

Carbachol, an agonist at muscarinic receptors, exerts a negative inotropic effect in human atrium. Carbachol can activate protein phosphatases (PP1 or PP2A). We hypothesized that cantharidin or sodium fluoride, inhibitors of PP1 and PP2A, may attenuate a negative inotropic effect of carbachol. During bypass-surgery trabeculae carneae of human atrial preparations (HAP) were obtained. These trabeculae were mounted in organ baths and electrically stimulated (1 Hz). Force of contraction was measured under isometric conditions. For comparison, we studied isolated electrically stimulated left atrial preparations (LA) from mice. Cantharidin (100 µM) and sodium fluoride (3 mM) increased force of contraction in LA (n = 5-8, p < 0.05) by 113% ± 24.5% and by 100% ± 38.2% and in HAP (n = 13-15, p < 0.05) by 625% ± 169% and by 196% ± 23.5%, respectively. Carbachol (1 µM) alone exerted a rapid transient maximum negative inotropic effect in LA (n = 6) and HAP (n = 14) to 46.9% ± 3.63% and 19.4% ± 3.74%, respectively (p < 0.05). These negative inotropic effects were smaller in LA (n = 4-6) and HAP (n = 9-12) pretreated with 100 µM cantharidin and amounted to 58.0% ± 2.27% and 59.2% ± 6.19% or 3 mM sodium fluoride to 63.7% ± 9.84% and 46.3% ± 5.69%, (p < 0.05). We suggest that carbachol, at least in part, exerts a negative inotropic effect in the human atrium by stimulating the enzymatic activity of PP1 and/or PP2A.

Nigella sativa oil restores hormonal levels, and endocrine signals among thyroid, ovarian, and uterine tissues of female Wistar rats following sodium fluoride toxicity.

The current study aimed to explore the possible prophylactic and therapeutic effect of Nigella sativa L. oil (NSO) against disruption of endocrine signals and injuries in the thyroid gland, ovary, and uterine tissues induced by sodium fluoride (NaF). Twenty-eight mature female Wistar rats were randomly allocated into four experimental groups (n = 7/group) as follows: control group; NaF group, orally received NaF (20 mg/kg b.wt.) daily; NSO/NaF, orally received NSO (300 mg/kg b.wt.) two weeks before being given NaF and continued throughout the experiment; and NSO+NaF group orally received NSO concurrently with NaF. Our results indicated that NSO restored hormonal balance and suppressed oxidative damage and inflammation. Moreover, the levels of triiodothyronine, thyroxine, thyroid peroxidase, estrogen (E2), progesterone, follicle-stimulating hormone, and luteinizing hormone were elevated, while prostaglandins F2-α and cortisol levels were decreased in NSO treated groups compared to NaF-intoxicated rats. As well, NSO significantly boosted levels of antioxidant molecules, and lowered lipid peroxidation of examined tissues, unlike NaF-treated group. NSO also up-regulated antioxidant enzymes, anti-apoptotic protein, zona pellucida sperm-binding protein, bone morphogenetic protein, and thyroid stimulating hormone, conversely down-regulated inflammatory cytokines, apoptotic proteins, estrogen receptor-α, estrogen receptor-ß, and thyroid stimulating hormone receptors compared to NaF-intoxicated group. Additionally, NSO ameliorated tissue damage of the thyroid gland, ovary, and uterus induced by NaF. -Overall, the prophylactic group (NSO/NaF) performed better antioxidant and anti-inflammatory activities than the treated group almost in all examined tissues, which is reflected by the improvement in the structure of the thyroid, ovarian, and uterine tissues.

Ameliorative effects of nano Moringa on fluoride-induced testicular damage via down regulation of the StAR gene and altered steroid hormones.

Fluoride is a common environmental contaminant that has harmful effects on human health when it is present in high concentrations. Fluoride enters the bloodstream after being absorbed by the gastrointestinal system when fluoride-contaminated groundwater is consumed by people. The aim of the present study was to determine whether polyphenol-rich nano Moringa oleifera (NMO) could protect rat testicles from sodium fluoride (NaF) damage by evaluating sperm quality, sex hormones, testicular oxidative status, histopathology, and StAR gene expression. Twenty-eight adult Wistar rats were divided equally and randomly into four groups: group one received distilled water; group two received NMO at a dosage of 250 mg/kg/body weight; group three received NaF at a dosage of 10 mg/kg/body weight; and group four received NaF and NMO. The rats were orally administrated daily for a duration of eight weeks. The study's findings demonstrated that, in comparison to rats exposed to NaF alone, co-administration of NMO and NaF enhanced sperm motility and viability, decreased sperm morphological changes, restored the balance between oxidant and antioxidant status, improved testosterone and dehydroepiandrosterone, improved testicular histology, raised the Johnson score, and upregulated the StAR gene in testicular tissue. These findings show that NMO is promise as a prophylactic medication against sodium fluoride-induced testicular damage because administration of NMO had no adverse effects and enhanced reproductive health.

18F-Sodium Fluoride PET/CT in Assessing Valvular Heart and Atherosclerotic Diseases.

Aortic valve stenosis is the most common valvular disease in Western countries, while atherosclerotic cardiovascular disease is the foremost cause of death and disability worldwide. Valve degeneration and atherosclerosis are mediated by inflammation and calcification and inevitably progress over time. Computed tomography can visualise the later stages of macroscopic calcification but fails to assess the early stages of microcalcification and cannot differentiate active from burnt out disease states. Molecular imaging has the ability to provide complementary information related to disease activity, which may allow us to detect disease early, to predict disease progression and to monitor preventive or therapeutic strategies for in both aortic stenosis and atherosclerosis. PET/CT is a non-invasive imaging technique that enables visualization of ongoing molecular processes within small structures, such as the coronary arteries or heart valves. 18F-sodium fluoride (18F-NaF) binds hydroxyapatite deposits in the extracellular matrix, with preferential binding to newly developing deposits of microcalcification, which provides an assessment of calcification activity. In recent years, 18F-NaF has attracted the attention of many research groups and has been evaluated in several pathological cardiovascular processes. Histologic validation of the 18F-NaF PET signal in valvular disease and atherosclerosis has been reported in multiple independent studies. The selective high-affinity binding of 18F-NaF to microscopic calcified deposits (beyond the resolution of µCT) has been demonstrated ex vivo, as well as its ability to distinguish between areas of macro- and active microcalcification. In addition, prospective clinical studies have shown that baseline 18F-NaF uptake in patients with aortic stenosis and mitral annular calcification is correlated with subsequent calcium deposition and valvular dysfunction after a follow-up period of 2 years. In patients with surgical bioprosthetic aortic valves but without morphological criteria for prosthetic degeneration, increased 18F-NaF uptake at baseline was associated with subsequent bioprosthetic degeneration over time. Similar data were obtained in a cohort of patients with transcatheter aortic valve implantation. Furthermore, several studies have confirmed the association of coronary 18F-NaF uptake with adverse atherosclerotic plaque features, active disease and future disease progression. 18F-NaF uptake is also associated with future fatal or nonfatal myocardial infarction in patients with established coronary artery disease. The link between 18F-NaF uptake and active atherosclerotic disease has not only been demonstrated in the coronary arteries, but also in peripheral arterial disease, abdominal aortic aneurysms and carotid atherosclerosis. It can be assumed that 18F-NaF PET/CT will strengthen the diagnostic toolbox of practitioners in the coming years. Indeed, there is a strong medical need to diagnose degenerative valvular disease and to detect active atherosclerotic disease states. Finally, the use of 18F-NaF as a biomarker to monitor the efficacy of drug therapies in preventing these pathological processes is attractive. In this review, we consider the role of 18F-NaF PET/CT imaging in cardiac valvular diseases and atherosclerosis.

Bone Turnover, Mineralization, and Volume Estimated by 18F-Sodium Fluoride PET/CT and Biomarkers in Chronic Kidney Disease: Mineral and Bone Disorder Compared with Bone Biopsy.

INTRODUCTION: Invasive bone biopsy to assess bone metabolism in patients with chronic kidney disease-mineral and bone disorder may be replaced by the noninvasive 18F-NaF PET/CT and biomarkers of bone metabolism. We aimed to compare parameters of bone turnover, mineralization, and volume assessed by bone biopsies with results derived from 18F-NaF PET/CT and biomarkers (bone-specific alkaline phosphatase, osteocalcin, fibroblast growth factor 23, and osteoprotegerin). METHODS: A cross-sectional study included 17 dialysis patients, and results from 18F-NaF PET/CT scans and the biomarkers were directly compared with the results of histomorphometric analyses of tetracycline double-labeled trans-iliac bone biopsies. RESULTS: Bone biopsies showed 40% high, 20% normal, and 40% low bone turnover. No biopsies had generalized abnormal mineralization, and the bone volume/total tissue volume was low in 80% and high in 7%. The pelvic skeletal plasma clearance (Ki) from 18F-NaF PET/CT correlated with bone turnover parameters obtained by bone biopsy (activation frequency: r = 0.82, p < 0.01; bone formation rate/bone surface: r = 0.81, p < 0.01), and Ki defined low turnover with high sensitivity (83%) and specificity (100%). CT-derived radiodensity correlated with bone volume, r = 0.82, p < 0.01. Of the biomarkers, only osteocalcin showed a correlation with turnover assessed by histomorphometry. CONCLUSION: In conclusion, 18F-NaF PET/CT may be applicable for noninvasive assessment of bone turnover and volume in CKD-MBD.

High concentration of sodium fluoride in drinking water induce hypertrophy versus atrophy in mouse skeletal muscle via modulation of sarcomeric proteins.

Fluoride at high doses is a well-known toxic agent for the musculoskeletal system, primarily in bone and cartilage cells. Research on fluoride toxicity concerning particularly on the skeletal muscle is scanty. We hypothesized that during skeletal fluorosis, along with bone, muscle is also affected, so we have evaluated the effects of Sodium fluoride (NaF) on mouse skeletal muscles. Sodium fluoride (80 ppm) was administered to 5-week-old C57BL6 mice drinking water for 15 and 60 days, respectively. We carried out histology, primary culture, molecular and proteomic analysis of fluoride administered mouse skeletal muscles. Results indicated an increase in the muscle mass (hypertrophy) in vivo and myotubes ex vivo by activating the IGF1/PI3/Akt/mTOR signalling pathway due to short term NaF exposure. The long-term exposure of mice to NaF caused loss of muscle proteins leading to muscle atrophy due to activation of the ubiquitin-proteasome pathway. Differentially expressed proteins were characterized and mapped using a proteomic approach. Moreover, the factors responsible for protein synthesis and PI3/Akt/mTOR pathway were upregulated, leading to muscle hypertrophy during the short term NaF exposure. Long term exposure to NaF resulted in down-regulation of metabolic pathways. Elevated myostatin resulted in the up-regulation of the muscle-specific E3 ligases-MuRF1, promoting the ubiquitination and proteasome-mediated degradation of critical sarcomeric proteins.

Sodium Fluoride-18 and Radium-223 Dichloride Uptake Colocalize in Osteoblastic Mouse Xenograft Tumors.

Background: Patients with osteoblastic bone metastases are candidates for radium-223 (223RaCl2) therapy and may undergo sodium fluoride-18 (18F-NaF) positron emission tomography-computed tomography imaging to identify bone lesions. 18F-NaF has been shown to predict 223RaCl2 uptake, but intratumor distributions of these two agents remain unclear. In this study, the authors evaluate the spatial distribution and relative uptakes of 18F-NaF and 223RaCl2 in Hu09-H3 human osteosarcoma mouse xenograft tumors at macroscopic and microscopic levels to better quantify their correlation. Materials and Methods: 18F-NaF and 223RaCl2 were co-injected into Hu09-H3 xenograft tumor severe combined immunodeficient mice. Tumor content was determined from in vivo biodistributions and visualized by PET, single photon emission computed tomography, and CT imaging. Intratumor distributions were visualized by quantitative autoradiography of tumor tissue sections and compared to histology of the same or adjacent sections. Results: 18F and 223Ra accumulated in proportional amounts in whole Hu09-H3 tumors (r2 = 0.82) and in microcalcified regions within these tumors (r2 = 0.87). Intratumor distributions of 18F and 223Ra were spatially congruent in these microcalcified regions. Conclusions: 18F-NaF and 223RaCl2 uptake are strongly correlated in heterogeneously distributed microcalcified regions of Hu09-H3 xenograft tumors, and thus, tumor accumulation of 18F is predictive of 223Ra accumulation. Hu09-H3 xenograft tumors appear to possess certain histopathological features found in patients with metastatic bone disease and may be useful in clarifying the relationship between administered 223Ra dose and therapeutic effect.

18F-NaF Uptake in Breast Cancer.

A 55-year-old woman with back pain underwent F-NaF PET/CT study to evaluate bone metastases from newly diagnosed breast cancer. Multiple foci of increased tracer uptake indicating osteoblastic metastases were noted in cervical and thoracic vertebrae. Unexpectedly, breast cancer also revealed increased NaF activity.

La exposición prenatal a fluoruro induce cambios en la porción coronal de la cripta ósea y altera la erupción dental en crías lactantes / Prenatal fluoride exposure induces changes in the coronal portion of bony crypt and alters dental eruption in suckling rats

La erupción dental es un proceso estrictamente regulado y programado espacial y temporalmente. El objetivo del trabajo fue estudiar el efecto de la exposición prenatal a fluoruro de sodio (NaF) sobre los eventos morfológicos y celulares que ocurren en el hueso supracoronal del primer molar de crías de rata durante la etapa preeruptiva. Se emplearon crías (n=6-8 por grupo) provenientes de madres que bebieron crónicamente agua con diferentes concentraciones de F- en forma de NaF durante la gestación y lactancia: control y NaF (50 mg/L). En cortes histológicos de la mandíbula de crías de 3 y 10 días se analizaron parámetros de histomorfometría estática en la zona supracoronal de la canastilla ósea a la altura del primer molar inferior: volumen óseo trabecular [BV/TV (%)], número de osteoclastos por milímetro (N.Oc/mm) y las variables indirectas: número de trabéculas [Tb.N (1/mm)], espesor [Tb.Th (µm)] y separación trabecular [Tb.Sp (µm)]. En crías de 15 días se midió el grado de erupción [TED (µm)] del primer molar inferior. Los resultados se analizaron con el test "t" de Student considerando diferencias significativas a p<0,05. El análisis histomorfométrico demostró un incremento en el BV/TV (%) del hueso supracoronal (p<0,01) asociado con disminución del N.Oc/mm (p<0,01) en crías de 3 y 10 días expuestas prenatalmente al F-. El grado de erupción dental fue menor en animales expuestos prenatalmente al F- en comparación con los controles (p<0,01). En conclusión, los resultados observados en la mandíbula de crías expuestas durante la etapa prenatal y posnatal temprana al F- sugieren un efecto disruptivo sobre la actividad resortiva necesaria para formación del canal eruptivo. (AU)

Tooth eruption is a tightly regulated and spatially and temporally programmed process. The aim of this study was to examine the effect of prenatal NaF exposure on the morphological and cellular events that occur in the supracoronal area of bony crypt of the first rat molar during the preeruptive stage. Offspring from two groups of rats were used (6-8 per group): Control and 50 mg/L NaF. The treatment was performed during pregnancy and lactation. Suckling pups were euthanized at 3-, 10- and 15-days-old by cervical dislocation. Mandibles were removed and histologically processed to obtain buccolingual sections stained with H&E. In sections of first mandibular molar of 3- and 10-days-old pups, the following static histomorphometric parameters were evaluated: trabecular bone volume [BV/TV (%)] and number of osteoclasts (N.Oc/mm). Also, indirect parameters were obtained: trabecular number [Tb.N (1/mm)], trabecular thickness [Tb.Th (µm)], and trabecular separation [Tb.Sp (µm)]. The degree of tooth eruption [TED (µm)] was determined. Results are expressed as mean ± SE and analyzed by Student t-test. Histomorphometric analysis showed an increase in the BV/TV (%) of the bone crypt of 3- and 10- days-old pups exposed to NaF (p <0.01); this increase was associated with a decrease in the N.Oc/mm (p <0.01). TED of mandibular first molar was lower in prenatal NaF exposed group than in control group (p<0.01). In conclusion, the increased BV/TV and the lower N.Oc observed in the bone crypt of 3- and 10- days-old pups from mothers treated with NaF suggested a disruptive effect triggered by F- on the formation events of the eruptive pathway in the offspring. (AU)

18F-NaF Uptake in Ocular Prosthesis (Implant).

Ocular prosthesis is used as a replacement in the orbit following enucleation or evisceration of the eye. Polymethyl methacrylate (PMMA), hydroxyapatite (HA) and porous polyethylene (PP) are some examples of the materials used in ocular prosthesis. We present a case of an 82-year-old man with prostate cancer who underwent F-NaF PET/CT imaging for evaluation of bone metastases and was incidentally found to have increased NaF uptake in the ocular prosthesis.

18F-NaF Uptake in Retroperitoneal Neurofibroma and Uterine Leiomyoma Calcifications.

A 48-year-old woman with intermittent lower back pain for 9 months and known retroperitoneal neurofibroma underwent F-NaF PET/CT scan to assess possible bony lesions causing the pain. Incidentally, the images showed elevated NaF activity in the retroperitoneal neurofibroma. In addition, uterine leiomyoma with heterogeneous calcifications revealed increased NaF activity.

Excess dietary fluoride affects laying performance, egg quality, tissue retention, serum biochemical indices, and reproductive hormones of laying hens.

The present study aimed to evaluate the effects of excess dietary fluoride (F) on laying performance, egg quality, tissue retention, serum biochemical indices, and serum reproductive hormones of laying hens. A total of 384 Hy-Line Gray hens, 37 wk old, were treated with sodium fluoride added to a corn-soybean meal basal diet at 0, 400, 800, and 1200 mg fluorine/kg feed. The results showed that dietary F levels at 800 and 1200 mg/kg markedly decreased ADFI, laying rate, average egg weight, and increased feed conversion ratio (FCR) (P < 0.05). Dietary F levels at 800 and 1200 mg/kg dramatically decreased the egg quality of albumen height, yolk color, eggshell strength, and eggshell thickness, and on the 49th D, 400 mg/kg F group significantly decreased the eggshell strength, compared to those of control group. Fluoride residues in tissues of hens were increased significantly with the increase of dietary F supplemental levels (P < 0.05). Fluoride concentrations were generally high in feces, eggshell, tibia, kidney, and ovary, and the highest in feces, following with eggshell and tibia, lower in kidney and ovary, and the lowest in serum. Serum uric acid levels and alanine aminotransferase activity increased significantly (P < 0.05), and glucose, triglycerides, and phosphorus decreased significantly (P < 0.05) in response to dietary F concentration, compared to those of the control group, respectively. Dietary F supplementation at 1200 mg/kg significantly decreased (P < 0.05) the estrogen concentrations in serum, compared to those of the control group. Concentrations of progesterone in the fluoride-treated groups were significantly (P < 0.05) decreased relative to those of the control group. In conclusion, these results indicated that the excessive ingestion of F has had a detrimental effect on egg laying rate and quality of eggs by damaging the function of the liver, kidney, and ovary of laying hens.

Normal Variant 18F-Sodium Fluoride Uptake in the Falx Cerebri Ossification.

Falx cerebri ossification is an incidental finding. Mostly it is easy to diagnose, but can be challenging in few cases, and should be distinguished from calcified meningioma, hematoma, and meningeal infiltration. We report a case of a 46-year-old woman with breast cancer complaining of back pain. F-NaF PET/CT images show focal increase uptake at facet joints of L5/S1 vertebrae and both knees joints, suggesting degenerative disease. There is normal variant F-NaF uptake noted in the ossification at the falx cerebri. Recognition of normal and abnormal extraosseous F-NaF uptake is important for correct interpretation to avoid unnecessary further investigations.

18F-NaF Uptake in Calcified Uterine Leiomyoma.

Uterine leiomyomas (fibroids) represent the most common benign pelvic tumors in women as well as the leading indication for hysterectomies in the United States. Risk factors for the development of fibroids include increasing age, hormonal changes, genetics, and race, among others. The lifetime risk of developing fibroids is greater than 80% among African American women, who also have the more severe form of this condition. We are presenting a case of incidental F-NaF uptake in the calcified uterine leiomyoma of a 52-year-old African American woman.

Comprehensive molecular imaging of malignant transformation of giant cell tumour of bone reveals diverse disease biology.

Malignant transformation of giant cell tumour of the bone is extremely rare. In addition, bone transformation in giant cell tumour may occur in different phases. With conventional X-rays, CT scans or MRIs, it may be challenging to distinguish among different phases of bone transformation, normal bone, soft tissue disease and bone disease (benign vs malignant lesions) and changes in multiple organs such as lung, liver and lymph nodes unless every lesion is biopsied, which is not practical. Molecular imaging with different isotopes (Tc-99m phosphonate, 2-deoxy-2-(18F)fluoro-d-glucose and sodium fluoride-18) may help to better characterise the disease. We hypothesised that molecular imaging could offer qualitative and quantitative characterisation of all stages of bone formation, destruction, reactivity or neoplasia in a patient with giant cell tumour of the bone, and we present the first case of molecular imaging where bone formation was seen in multiple soft tissues, such as lungs, muscles, lymph nodes and liver.

Correlation of fluorine 18-labeled sodium fluoride uptake and arterial calcification on whole-body PET/CT in cancer patients.

BACKGROUND: Fluorine-18-labeled sodium fluoride (F-NaF) uptake measured with PET in the vessel walls can indicate active microcalcification, a potential biomarker of higher-risk plaques, which are not indicated by macrocalcification measured with computed tomography (CT). The aim of this study was to determine the extent to which F-NaF uptake is correlated with calcification at arterial plaques in cancer patients undergoing whole-body PET/CT imaging. PATIENTS AND METHODS: Image data from 179 patients who underwent F-NaF PET/CT were evaluated retrospectively. Plaques were categorized into four groups by calcium score (CS) on CT: CS1 (≥1000); CS2 (400-999); CS3 (100-399), and CS4 (<100) and into three groups by F-NaF target-to-background ratio (TBR) on PET: TBRlow (≤1.0), TBRmedium (1.0-1.5), and TBRhigh (>1.5). Correlations between F-NaF uptake and CS were evaluated. RESULTS: Plaques with F-NaF uptake or arterial calcification were observed in 122 (76%) of the 179 patients. We found a weak but statistically significant positive correlation between CS and F-NaF uptake. The TBR in CS1 plaques was higher than those in CS3 and CS4 plaques, and the TBR in CS2 plaques was higher than that in CS3 plaques (P<0.05). Compared with patients whose plaques were with F-NaF uptake (TBR>1.5) or arterial calcification (CS>0), patients without plaques of F-NaF uptake or calcification were significantly younger (P=0.00) or with significantly more women (P=0.02). CONCLUSION: Our finding of a weak but significant positive correlation between F-NaF uptake and arterial calcification suggests that F-NaF PET/CT could provide complementary information of active microcalcification for atherosclerosis evaluation in cancer patients.

Response-to-repeatability of quantitative imaging features for longitudinal response assessment.

Quantitative imaging biomarkers (QIBs) are often selected and ranked based on their repeatability performance. In the context of treatment response assessment, however, one must also consider how sensitive a QIB is to measuring changes in the tumour. This work introduces response-to-repeatability ratio (R/R), which weighs the ability of a QIB to detect significant changes with respect to its measurement repeatability and applies it to the case of PET texture features. R/R is evaluated as the proportion of measurable changes from baseline to follow-up for each candidate QIB. We analyse 47 texture features extracted from lesions in bone-metastatic prostate cancer patients who received double baseline and/or baseline to treatment follow-up 18F-NaF PET/CT scans. R/R evaluates the proportion of follow-up changes outside of the 95% limits of agreement (LOA) defined by test-retest values. Intraclass correlation coefficient (ICC) and coefficient of variation (CV) are calculated for each feature. Relationship between ICC and R/R are evaluated with the Spearman's correlation coefficient. R/R varied significantly across texture features: 41/47 (87%) features demonstrated R/R > 5%; 21/47 (45%) features demonstrated R/R > 10%, and 11/47 (23%) features demonstrated R/R > 20%. LOA of features ranged from [0.998, 1.001] to [0.22, 4.86]. Repeatability alone did not qualify a feature for its efficacy at detecting measurable change at follow-up, as shown by weak correlations between R/R and both CV and ICC (ρ = 0.23 and ρ = 0.40, respectively). Three features demonstrated excellent ICC (ICC > 0.75) and R/R greater than that of SUVmax (R/R = 41.8%): skewness (ICC = 0.92, R/R = 75.4%), kurtosis (ICC = 0.88, R/R = 47.0%) and diagonal moment (ICC = 0.88, R/R = 45.5%). R/R characterizes the sensitivity of candidate QIBs to detect measurable changes at follow-up. R/R supplements existing precision performance metrics (e.g. CV, ICC, and LOA) as an index to assess the utility of QIBs for response assessment.

Incidental 18F-NaF Uptake in Drug-Induced Gynecomastia.

Gynecomastia is not uncommon in men older than 50 years of age and is characterized by glandular proliferation of breast tissue. Non-physiologic gynecomastia is mostly caused by a variety of external medical interventions. Medications that belong to classes of antiandrogens, antipsychotics, or antibiotics alter the levels of estrogen and testosterone and are commonly implicated in patients with gynecomastia. We are presenting a case of bilateral F-NaF uptake in the breast tissue of a 56-year-old man with known history of prostate cancer.

A Case of Glioblastoma With Calcified Region Imaged With 18F-NaF PET/CT.

F-NaF is a bone-seeking positron-emitting tracer with high sensitivity and specificity for detection of osseous lesions. We report a case of primary glial tumor that showed extraosseous uptake on F-NaF PET/CT. CT revealed a mass in the right parietal lobe with calcification. F-NaF PET/CT showed abnormal tracer uptake in the brain tumor, which was subsequently confirmed to be a glioblastoma by histologic examination.