Development of a new epidermal growth factor receptor positron emission tomography imaging agent based on the 3-cyanoquinoline core: Synthesis and biological evaluation

The epidermal growth factor receptor (EGFR/c-ErbB1/HER1) is overexpressed in many cancers including breast, ovarian, endometrial, and non-small cell lung cancer. An EGFR specific imaging agent could facilitate clinical evaluation of primary tumors and/or metastases. To achieve this goal we designed and synthesized a small array of fluorine containing compounds based on a 3-cyanoquinoline core. A lead compound, 16, incorporating 2′-fluoroethyl-1,2,3-triazole was selected for evaluation as a radioligand based on its high affinity for EGFR kinase (IC₅₀ = 1.81 ± 0.18 nM), good cellular potency (IC₅₀ = 21.97 ± 9.06 nM), low lipophilicity and good metabolic stability. ‘Click’ labeling afforded [¹⁸F]16 in 37.0 ± 3.6% decay corrected radiochemical yield based on azide [¹⁸F]14 and 7% end of synthesis (EOS) yield from aqueous fluoride. Compound [¹⁸F]16 was obtained with >99% radiochemical purity in a total synthesis time of 3 h. The compound showed good stability in vivo and a fourfold higher uptake in high EGFR expressing A431 tumor xenografts compared to low EGFR expressing HCT116 tumor xenografts. Furthermore, the radiotracer could be visualized in A431 tumor bearing mice by small animal PET imaging. Compound [¹⁸F]16 therefore constitutes a promising radiotracer for further evaluation for imaging of EGFR status.     

Rapid determination of 25-hydroxy vitamin D3 in swine tissue using an isotope dilution HPLC-MS assay

A rapid method for quantification of 25-hydroxy vitamin D3 in different swine tissues based on isotope dilution HPLC-MS has been developed and validated. Six times deuterated analyte is used as internal standard. The method is fast and can be performed with only 1 g sample. Sample preparation for kidney, liver, muscle and spleen requires only homogenisation and extraction with methanol. An additional enzymatic digest is required for skin, and clean-up of the extract by solid-phase extraction (SPE) is used for adipose tissue and skin. The lower limit of detection varies from 1 ng/g (muscle) to 5 ng/g (adipose and skin). The method has been successfully applied to various tissue samples of pigs fed for 119 days either 2000 IU of vitamin D3 or 50 μg of 25-hydroxy vitamin D3 per kg feed. For animals ingesting 25-OH-D3 supplements the highest tissue contents were observed in the skin (24.8 ± 3.5 ng/g), followed by kidney (14.2 ± 1.5 ng/g), liver and muscle (5.7 ± 0.6 ng/g). The 25-OH-D3 content in the skin was significantly higher in animals ingesting 2000 IU/kg of vitamin D3 (39.5 ± 13.4 ng/g). Levels in selected tissues of some animals were below the lower limit of quantification. No measurable amounts of 25-OH-D3 were found in spleen, abdominal fat and subcutaneous fat of the animals of both groups as well as in the liver, kidney and muscle of the animals ingesting 2000 IU/kg of vitamin D3.     

A novel approach to the measurement of surfactant parameters in arthropod digestive juices

In arthropods, the determination of two important parameters of digestive juices, i.e. the total surfactant concentration and the critical micelle concentration (CMC), is challenging due to small sample volumes and low surfactant concentrations. In this work, we report a successful implementation of potentiometric titrations using the surfactant ion-selective electrode (SISE) and the pyrene fluorescence method (PFM) for the determination of the total surfactant concentration and CMC in the digestive juice of terrestrial isopod crustaceans Porcellio scaber. Pooled digestive juice extracts of four (SISE) or two (PFM) animals were used per measurement run. In both cases, digestive juice extracts in 100 μL of deionized water were sufficient for one measurement run. The total surfactant concentration of P. scaber digestive juice was determined to be 9.2 ± 3.5 mM and the CMC was approximately 90 μM. Our work presents an important improvement towards easy CMC determination in small volume samples in comparison with the commonly used stalagmometric technique, where much larger sample volumes are usually needed. To date, the total surfactant concentration was not measured in the digestive juices of arthropods other than Homarus vulgaris, Astacus leptodactylus and Cancer pagurus, for which complex separation and analytical techniques were required. Our results obtained by SISE and PFM therefore present the first successful quantification of surfactants and their CMC in small volumes of arthropod digestive juice without prior separation or purification techniques.     

Measuring three-dimensional knee kinematics under torsional loading

Excessive knee joint laxity is often used as an indicator of joint disease or injury. Clinical assessment devices are currently limited to anterior–posterior drawer measurements, while tools used to measure movement in the remaining degrees of freedom are either invasive or prone to soft tissue artefact. The objective of this work was, therefore, to develop a methodology whereby in vivo knee joint kinematics could be measured in three dimensions under torsional loading while still maintaining a non-invasive procedure. A device designed to administer a subject-normalized torque in the transverse plane of the knee was securely fastened to the outer frame of an open magnetic resonance imaging (MRI) magnet. Low resolution 3D T1-weighted images (6.25 mm slice thickness) were generated by the 0.2 Tesla MRI scanner in less than 3 min while the joint was under load. The 3D image volume was then shape-matched to a high resolution image volume (1.56 mm slice thickness) scanned in a no-load position. Three-dimensional rotations and translations of the tibia with respect to the femur were calculated by comparing the transformation matrices before and after torque was applied. Results from six subjects showed that this technique was repeatable over five trials with the knee in extended and flexed positions. Differences in range of rotation were shown between subjects and between knee positions, suggesting that this methodology has sufficient utility for further application in clinical studies.     

Net and metabolizable protein requirements for body weight gain in hair and wool lambs

Protein is one of the limiting factors in animal production, and the knowledge of protein requirements by livestock is crucial for the success of a commercial animal raising enterprise. Thirty-four castrated lambs, 17 of them F1 Ideal × Ile de France wool lambs and the remaining ones were Santa Inês hair lambs, with homogeneous initial BW, were used in the experiment. Five animals from each genotype were slaughtered in the beginning of the experimental period and used as reference. Diets (D) were composed of concentrate mix (C) and Cynodon sp. c.v. Tifton 85 hay (R), combined in three different ratios: D1 = 60C:40R; D2 = 40C:60R and D3 = 20C:80R. Animals of each group of three lambs, that showed simultaneously an initial BW of 20 ± 0.14 kg at the beginning of the dietary regimen, were slaughtered when one of them reached 35 kg, what always happened to be the one fed with D1. Net requirements for BW gain in wool lamb, fleece-free, ranged from 101 to 110 g of protein/kg BW, and for hair lamb ranged from 110 to 118 g of protein/kg BW. Net protein requirements for wool production ranged from 634 to 642 g/kg of produced wool. Hair lambs presented a 7.8–9.5% higher estimated net protein requirements than wool lambs, according to BW and daily weight gain (DG). Total net protein requirements for Santa Inês and wool lambs, with 30 kg of initial BW and an approximate 200 g mean DG, were 48.5 and 45.4 g/day, respectively. Metabolizable protein requirements for Santa Inês and wool lambs, with 20 kg of initial BW and an approximate 200 g mean DG were 59.4 g and 76.5 g/day, respectively. Net protein requirements for wool production was 64 g/100 g of produced wool. Thus, under the conditions of this experiment, it is concluded that hair lambs showed a higher concentration of protein in the body, more efficient use of the ingested protein and a consequent additional BW gain when fed isoproteic diets as compared to F1 Ideal × Ile de France wool lambs.     

Impact of coronal and sagittal views on lung gross tumor volume delineation

Background and purposeTo study the impact of coronal and sagittal views (CSV) on the gross tumor volume (GTV) delineation on CT and matched PET/CT scans in non-small cell lung cancer.Material and methodsGTV delineations were performed by 11 experienced radiation oncologists on CT and PET/CT in 22 patients. Two tumor groups were defined: Group I: Primary tumors surrounded by lung or visceral pleura, without venous invasion, and without large extensions to the chest wall or the mediastinum. Group II: Tumors invading the hilar region, heart, large vessels, pericardium, and the mediastinum and/or associated with atelectasis. Tumor volumes and inter-observers variations (SD) were calculated and compared according to the use of axial view only (AW), axial/coronal/sagittal views (ACSW) and ACSW/PET (ACSWP).ResultsCSV were not frequently used (57.4% out of 242 delineations on CT). For group I, ACSW didn’t improve significantly mean GTVs. SDs were small on CT and on PET (SD = 0.3 cm). For group II, ACSW had 27–46% smaller observer variation (mean SD = 0.7 cm) than AW (mean SD = 1.1 cm). The smaller observer variation of ACSW users was associated with, on average, a 40% smaller delineated volume (p = 0.038). Mean GTV of ACSWP was 21% larger than mean GTV of ACSW on CT.ConclusionsFor smaller lung tumors surrounded by healthy lung tissue the effect of multiple axis delineation is limited. However, application of coronal and sagittal windows is highly beneficial for delineation of more complex tumors, with atelectasis and/or pathological lymph nodes even if PET is used.     

Effect of patient positioning on carbon-ion therapy planned dose distribution to pancreatic tumors and organs at risk

PurposePancreatic tumor treatment dose distribution variations associated with supine and prone patient positioning were evaluated.MethodsA total of 33 patients with pancreatic tumors who underwent CT in the supine and prone positions were analyzed retrospectively. Gross tumor volume (GTV), planning target volume (PTV), and organs at risk (OARs) (duodenum and stomach) were contoured. The prescribed dose of 55.2 Gy (RBE) was planned from four beam angles (0°, 90°, 180°, and 270°). Patient collimator and compensating boli were designed for each field. Dose distributions were calculated for each field in the supine and prone positions. To improve dose distribution, patient positioning was selected from supine or prone for each beam field.ResultsCompared with conventional beam angle and patient positioning, D2cc of 1st-2nd portion of duodenum (D1-D2), 3rd-4th portion of duodenum (D3-D4), and stomach could be reduced to a maximum of 6.4 Gy (RBE), 3.5 Gy (RBE), and 4.5 Gy (RBE) by selection of patient positioning. V10 of D1-D2, D3-D4, and stomach could be reduced to a maximum of 7.2 cc, 11.3 cc, and 11.5 cc, respectively. D95 of GTV and PTV were improved to a maximum of 6.9% and 3.7% of the prescribed dose, respectively.ConclusionsOptimization of patient positioning for each beam angle in treatment planning has the potential to reduce OARs dose maintaining tumor dose in pancreatic treatment.     

Non-closure of peritoneum after abdominal hysterectomy for uterine carcinoma does not increase late intestinal radiation morbidity

Background/AimTo evaluate whether non-closure of the visceral peritoneum after total abdominal hysterectomy (TAH) and bilateral salpingo-oophorectomy (BSO) in patients with uterine corpus carcinoma influences the volume of the small intestine within the irradiated volume during adjuvant radiotherapy or late radiation intestinal toxicity.Materials and methodsA total of 152 patients after TAH + BSO with adjuvant pelvic radiotherapy were studied. The state of peritonealization was retrospectively evaluated based on surgical protocols. The volume of irradiated bowels was calculated by CT-based delineation in a radiotherapy planning system. The influence of visceral peritonealization upon the volume of the small intestine within the irradiated volume and consequent late morbidity was analyzed.ResultsVisceral peritonealization was not performed in 70 (46%) of 152 studied patients. The state of peritonealization did not affect the volume of the irradiated small intestine (p = 0.14). Mean volume of bowels irradiated in patients with peritonealization was 488 cm³ (range 200–840 cm³, median 469 cm³); mean volume of bowels irradiated in patients without peritonealization was 456 cm³ (range 254–869 cm³, median 428 cm³). We did not prove any significant difference between both arms. Nor did we observe any influence of non-peritonealization upon late intestinal morbidity (p = 0.34).ConclusionNon-closure of the visceral peritoneum after hysterectomy for uterine corpus carcinoma does not increase the volume of the small intestine within the irradiated volume, with no consequent intestinal morbidity enhancement.     

Vitamin D sufficiency associates with an increase in anti-inflammatory cytokines after intense exercise in humans

The purpose of this study was to identify the influence of vitamin D status (insufficient vs. sufficient) on circulating cytokines and skeletal muscle strength after muscular injury. To induce muscular injury, one randomly selected leg (SSC) performed exercise consisting of repetitive eccentric–concentric contractions. The other leg served as the control. An averaged serum 25(OH)D concentration from two blood samples collected before exercise and on separate occasions was used to establish vitamin D insufficiency (<30 ng/mL, n = 6) and sufficiency (>30 ng/mL, n = 7) in young, adult males. Serum cytokine concentrations, single-leg peak isometric force, and single-leg peak power output were measured before and during the days following the exercise protocol. The serum IL-10 and IL-13 responses to muscular injury were significantly (both p < 0.05) increased in the vitamin D sufficient group. The immediate and persistent (days) peak isometric force (p < 0.05) and peak power output (p < 0.05) deficits in the SSC leg after the exercise protocol were not ameliorated with vitamin D sufficiency. We conclude that vitamin D sufficiency increases the anti-inflammatory cytokine response to muscular injury.     

Radiological properties of 3D printed materials in kilovoltage and megavoltage photon beams

PurposeThis study evaluates the radiological properties of different 3D printing materials for a range of photon energies, including kV and MV CT imaging and MV radiotherapy beams.MethodsThe CT values of a number of materials were measured on an Aquilion One CT scanner at 80 kVp, 120 kVp and a Tomotherapy Hi Art MVCT imaging beam. Attenuation of the materials in a 6 MV radiotherapy beam was investigated.ResultsPlastic filaments printed with various infill densities have CT values of −743 ± 4, −580 ± 1 and −113 ± 3 in 120 kVp CT images which approximate the CT values of low-density lung, high-density lung and soft tissue respectively. Metal-infused plastic filaments printed with a 90% infill density have CT values of 658 ± 1 and 739 ± 6 in MVCT images which approximate the attenuation of cortical bone. The effective relative electron density RED_eff is used to describe the attenuation of a megavoltage treatment beam, taking into account effects relating to the atomic number and mass density of the material. Plastic filaments printed with a 90% infill density have RED_eff values of 1.02 ± 0.03 and 0.94 ± 0.02 which approximate the relative electron density RED of soft tissue. Printed resins have RED_eff values of 1.11 ± 0.03 and 1.09 ± 0.03 which approximate the RED of bone mineral.Conclusions3D printers can model a variety of body tissues which can be used to create phantoms useful for both imaging and dosimetric studies.     

Accuracy map of an optical motion capture system with 42 or 21 cameras in a large measurement volume

Optical motion capture is commonly used in biomechanics to measure human kinematics. However, no studies have yet examined the accuracy of optical motion capture in a large capture volume (>100 m³), or how accuracy varies from the center to the extreme edges of the capture volume. This study measured the dynamic 3D errors of an optical motion capture system composed of 42 OptiTrack Prime 41 cameras (capture volume of 135 m³) by comparing the motion of a single marker to the motion reported by a ThorLabs linear motion stage. After spline interpolating the data, it was found that 97% of the capture area had error below 200 μm. When the same analysis was performed using only half (21) of the cameras, 91% of the capture area was below 200 μm of error. The only locations that exceeded this threshold were at the extreme edges of the capture area, and no location had a mean error exceeding 1 mm. When measuring human kinematics with skin-mounted markers, uncertainty of marker placement relative to underlying skeletal features and soft tissue artifact produce errors that are orders of magnitude larger than the errors attributed to the camera system itself. Therefore, the accuracy of this OptiTrack optical motion capture system was found to be more than sufficient for measuring full-body human kinematics with skin-mounted markers in a large capture volume (>100 m³).     

Online solid phase extraction with liquid chromatography–tandem mass spectrometry to analyze remoxipride in small plasma-, brain homogenate-, and brain microdialysate samples

Remoxipride is a selective dopamine D₂ receptor antagonist, and useful as a model compound in mechanism-based pharmacological investigations. To that end, studies in small animals with serial sampling over time are needed. For these small volume samples currently no suitable analytical methods are available. We propose analytical methods for the detection of low concentrations remoxipride in small sample volumes of plasma, brain homogenate, and brain microdialysate, using online solid phase extraction with liquid chromatography–tandem mass spectrometry. Method development, optimization and validation are described in terms of calibration curves, extraction yield, lower limit of quantification (LLOQ), precision, accuracy, inter-day- and intra-day variability. The 20 μl plasma samples showed an extraction yield of 76%, with a LLOQ of 0.5 ng/ml. For 0.6 ml brain homogenate samples the extraction yield was 45%, with a LLOQ of 1.8 ng/ml. The 20 μl brain microdialysate samples, without pre-treatment, had a LLOQ of 0.25 ng/ml. The precision and accuracy were well within the acceptable 15% range. Considering the small sample volumes, the high sensitivity and good reproducibility, the analytical methods are suitable for analyzing small sample volumes with low remoxipride concentrations.     

Scrotal,testicular and semen characteristics of young Boer bucks fed winter veld hay: The effect of nutritional supplementation

The aim of the work was to determine the effects of feeding winter veld hay plus a supplement on scrotal, testicular and semen characteristics in young Boer goat bucks. Fifteen Boer goat bucks (6–8 months of age), were allocated to two groups and fed ad libitum for a period of 29 days. The WH group (winter hay or control group; n = 8) received a chopped diet consisting of grass hay, predominantly Themeda triandra grass (cut during the winter) from natural pastures (veld). The WH + S group (winter hay plus supplement; n = 7) received the same diet consisting of Themeda triandra veld hay and supplemented with maize meal, molasses meal and urea. Body weights and feed intake were recorded, as well as scrotal, testicular and semen characteristics. Results indicate a detrimental effect of winter veld hay feeding on characteristics such as sperm cell abnormalities (43% in the WH group versus 24% in WH group), testicular volume (156 ml in the WH + S group versus 104 ml for WH animals) or scrotal circumference (20.7 cm in WH + S group versus 17.7 cm in WH group). It is essential to supplement the nutrition of small ruminants under winter environments, to maintain scrotal, testicular and semen characteristics, especially if the animals are to be used in the subsequent breeding season.     

Optimisation du protocole d’acquisition de la TEP à la fluorocholine dans la détection des lésions parathyroïdiennes

18F-Fluorocholine (FCH) PET/CT shows very promising potential for detection of hyperfunctioning parathyroid tumors. However, the optimal time to perform imaging after FCH administration has not yet been determined and protocols are highly variable. The aim of this study was to qualitatively and quantitatively compare 5, 10, 15, 20 and 60 min post-injection acquisition times in patients with primary hyperparathyroidism and equivocal traditional imaging. Thirty-one patients were included. Two observers retrospectively analyzed the five protocols. Any focal increase in FCH uptake was localized and graded on a discrete gradation scale between 1 and 5 to assess the likelihood of hyperfunctioning parathyroid tumors. Gold standard was histopathological findings for the 11 operated patients. Regarding quantitative analysis, ratio of SUVmax of parathyroid foci on SUVmean of thyroid background (as signal-to-noise ratio) were compared between protocols. After injection of 2.5 MBq/kg, FCH PET performed 60 min post-injection (2 min) had the best sensitivity and specificity by lesion (92% and 100% respectively and the best signal-to-noise ratio (median of 2). We suggest performing PET scan 60 min after injection, associated with early acquisition so as not to miss a wash-out hyperfunctioning parathyroid tumors.     

Poor glycemic control in type 2 diabetes enhances functional and compositional alterations of small,dense HDL3c

High-density lipoprotein (HDL) possesses multiple biological activities; small, dense HDL3c particles displaying distinct lipidomic composition exert potent antiatherogenic activities which can be compromised in dyslipidemic, hyperglycemic insulin-resistant states. However, it remains indeterminate (i) whether such functional HDL deficiency is related to altered HDL composition, and (ii) whether it originates from atherogenic dyslipidemia, dysglycemia, or both.In the present work we analyzed compositional characteristics of HDL subpopulations and functional activity of small, dense HDL3c particles in treatment-naïve patients with well-controlled (n = 10) and poorly-controlled (n = 8) type 2 diabetes (T2D) and in normolipidemic age- and sex-matched controls (n = 11).Our data reveal that patients with both well- and poorly-controlled T2D displayed dyslipidemia and low-grade inflammation associated with altered HDL composition. Such compositional alterations in small, dense HDL subfractions were specifically correlated with plasma HbA1c levels. Further analysis using a lipidomic approach revealed that small, dense HDL3c particles from T2D patients with poor glycemic control displayed additional modifications of their chemical composition. In parallel, antioxidative activity of HDL3c towards oxidation of low-density lipoprotein was diminished.These findings indicate that defective functionality of small, dense HDL particles in patients with T2D is not only affected by the presence of atherogenic dyslipidemia, but also by the level of glycemic control, reflecting compositional alterations of HDL.     

Megavoltage 2D topographic imaging: An attractive alternative to megavoltage CT for the localization of breast cancer patients treated with TomoDirect

PurposeTo show the usefulness of topographic 2D megavoltage images (MV2D) for the localization of breast cancer patients treated with TomoDirect (TD), a radiotherapy treatment technique with fixed-angle beams performed on a TomoTherapy system.MethodsA method was developed to quickly localize breast cancer patients treated with TD by registering the MV2D images produced before a TD treatment with reference images reconstructed from a kilovoltage CT simulation scanner and by using the projection of the beam-eye-view TD treatment field. Dose and image quality measurements were performed to determine the optimal parameters for acquiring MV2D images. A TD treatment was simulated on a chest phantom equipped with a breast attachment. MVCT and MV2D images were performed for 7 different shifted positions of the phantom and registered by 10 different operators with the simulation kilovoltage CT images.ResultsCompared to MVCT, MV2D imaging reduces the dose by a factor of up to 45 and the acquisition time by a factor of up to 49. Comparing the registration shift values obtained for the phantom images obtained with MVCT in the coarse mode to those obtained with MV2D, the mean difference is 1.0 ± 1.1 mm, −1.1 mm ± 1.1, and −0.1 ± 2.2 mm, respectively, in the lateral, longitudinal, and vertical directions.ConclusionsWith dual advantages (very fast imaging and a potentially reduced dose to the heart and contralateral organs), MV2D topographic images may be an attractive alternative to MVCT for the localization of breast cancer patients treated with TomoDirect.     

Neue Giraffenhaltung im Opel-Zoo Kronberg.

The „Africa Savanna“– exhibit is described. The biggest investment of the Opel-Zoo in recent years was opened for the public on the 50th anniversary of the so-called Georg von Opel – Freigehege für Tierforschung on September 16th, 2006. The developed area covers about 22500 m² and includes in addition to the animal related buildings, a new restaurant, a new main entrance and a new administration building. The mostly moated outside exhibit of about 10000 m² is dominated by artificial baobab tree. A waterhole of 200 m² separates the exhibit from the restaurant. Due to fairly long winters the inside area for the giraffes is rather large, so they can be kept as a herd, even when they must stay inside. Visitors can enter a small area of the giraffe house and may watch the animals through glass. The off-exhibit area for the zebras, gnus and impalas has 18 equal stables of 10 m² each. Five introduction pens connect the new animal house with the outside exhibit.This article also informs about the giraffe keeping history at Kronberg since 1961 and tells about the experiences made with the new development during the first year of use.     

Supplemental vitamin D increases serum cytokines in those with initially low 25-hydroxyvitamin D: A randomized,double blind,placebo-controlled study

The purpose of this study was to determine if vitamin D status before supplementation influences the cytokine response after supplemental vitamin D. Forty-six reportedly healthy adults (mean(SD); age, 32(7) y; body mass index (BMI), 25.3(4.5) kg/m²; serum 25-hydroxyvitamin D (25(OH)D), 34.8(12.2) ng/mL) were randomly assigned (double blind) to one of three groups: (1) placebo (n = 15), or supplemental vitamin D (cholecalciferol) at (2) 4000 (n = 14) or (3) 8000 IU (n = 17). Supplements were taken daily for 35 days. Fasting blood samples were obtained before (Baseline, Bsl) and 35-days after (35-d) supplementation. Serum 25(OH)D, 1,25-dihydroxyvitamin D (1,25(OH)D), cytokines, and intact parathyroid hormone with calcium were measured in each blood sample. Supplemental vitamin D increased serum 25(OH)D (4000 IU, ≈29%; 8000 IU, ≈57%) and 1,25(OH)D (4000 IU, ≈12%; 8000 IU, ≈38%) without altering intact parathyroid hormone or calcium. The vitamin D metabolite increases in the supplemental vitamin D groups (n = 31) were dependent on initial levels as serum 25(OH)D (r = −0.63, p < 0.05) and 1,25(OH)D (r = −0.45, p < 0.05) at Bsl correlated with their increases after supplementation. Supplemental vitamin D increased interferon (IFN)-γ and interleukin (IL)-10 in subjects that were vitamin D insufficient (serum 25(OH)D < 29 ng/mL) compared to sufficient (serum 25(OH)D ⩾ 30 ng/mL) at Bsl. We conclude that supplemental vitamin D increase a pro- and anti-inflammatory cytokine in those with initially low serum 25(OH)D.     

Confrontation des données de la TEP/TDM au 18FDG initiale aux statuts p16 (INK4a) et HPV des cancers des VADS localement avancés traités par radiochimiothérapie

PurposeThe overexpression of p16 and HPV status are now well established as independent prognostic factors in head and neck squamous cell carcinoma (HNSCC). It was suggested that some parameters derived from initial 18F-FDG PET are also independent prognostic factors. Our purpose was to study the correlation between virology and pretreatment PET/CT in locally advanced HNSCC treated by radio-chemotherapy.MethodsForty HNSCC patients with tumor volumes > 3 cm³ were prospectively recruited. All patients underwent initial 18F-FDG PET/CT, from which metabolic volume, intensity (SUV), overall activity, heterogeneity and shape parameters were extracted. The correlation of these parameters with virological data extracted from pre treatment biopsy, including p16 expression, DNA HPV 16 and HPV status (p16 + DNA HPV 16) was subsequently studied.ResultsP16 + tumors exhibited higher SUV_max (P = 0.028) and SUV_mean (P = 0.02). P16+ tumors were also more heterogeneous, albeit with a lower correlation (P = 0.004 for local heterogeneity). In addition, P16+ and HPV+ tumors were characterized by less complex shapes (P = 0.03).ConclusionLocally advanced HNSCC show specific PET characteristics in case of P16+ tumors. The relationship between those different biological characterization approaches and overall patient outcome needs to be investigated.