Chitosan microcapsules loaded with either miconazole nitrate or clotrimazole,prepared via emulsion technique

In this paper, a simple and versatile coacervation technique has been developed by using an ultrasound-assisted oil/water emulsion method for the preparation of antifungal agent-loaded microcapsules. Two types of chitosan microcapsules are successfully prepared. The mean particle size of the chitosan/miconazole nitrate microcapsules is 2.6 μm and that of the chitosan/clotrimazole microcapsules is 4.1 μm. The encapsulation efficiency of the chitosan/miconazole nitrate microcapsules (77.58–96.81%) is relatively higher than that of the chitosan/clotrimazole microcapsules (56.66–93.82%). The in vitro drug release performance of the microcapsules shows that the chitosan/miconazole nitrate microcapsules release about 49.5% of the drug while chitosan/clotrimazole microcapsules release more than 66.1% of the drug after 12 h under a pressure of 5 kg at pH 5.5, which is similar to the pH of human skin. The prepared drug-loaded microcapsules could be applied onto bandages or socks, and will continuously release antifungal drugs in a controlled manner under pressure.     

Fetal radiation dose in three common CT examinations during pregnancy – Monte Carlo study

PurposeTo determine fetal doses in different stages of pregnancy in three common computed tomography (CT) examinations: pulmonary CT angiography, abdomino-pelvic and trauma scan with Monte Carlo (MC) simulations.MethodsAn adult female anthropomorphic phantom was scanned with a 64-slice CT using pulmonary angiography, abdomino-pelvic and trauma CT scan protocols. Three different sized gelatin boluses placed on the phantom’s abdomen simulated different stages of pregnancy. Intrauterine dose was used as a surrogate to a dose absorbed to the fetus. MC simulations were performed to estimate uterine doses. The simulation dose levels were calibrated with volumetric CT dose index (CTDI_vol) measurements and MC simulations in a cylindrical CTDI body phantom and compared with ten point doses measured with metal-oxide-semiconductor field-effect-transistor dosimeters. Intrauterine volumes and uterine walls were segmented and the respective dose volume histograms were calculated.ResultsThe mean intrauterine doses in different stages of pregnancy varied from 0.04 to 1.04 mGy, from 4.8 to 5.8 mGy, and from 9.8 to 12.6 mGy in the CT scans for pulmonary angiography, abdomino-pelvic and trauma CT scans, respectively. MC simulations showed good correlation with the MOSFET measurement at the measured locations.ConclusionsThe three studied examinations provided highly varying fetal doses increasing from sub-mGy level in pulmonary CT angiography to notably higher levels in abdomino-pelvic and trauma scans where the fetus is in the primary exposure range. Volumetric dose distribution offered by MC simulations in an appropriate anthropomorphic phantom provides a comprehensive dose assessment when applied in adjunct to point-dose measurements.     

Radiation dose comparison between V/P-SPECT and CT-angiography in the diagnosis of pulmonary embolism

PurposeThe aim of this study is to compare two routine protocols at our institution, CTPA and V/P-SPECT, in terms of radiation dose to the most exposed organs (lungs and breast) and to the embryo/fetus in the case of pregnant patients.MethodsAt our institution, the CTPA protocol includes a contrast enhanced CT (scan parameters: 100 kVp, 700 mA, 0.5 s/rot, pitch 0.984) and in some cases a non-contrast enhanced CT acquisition (120 kVp, 400 mA, 0.5 s/rot, pitch 1.375).In the V/P-SPECT protocol, ventilation SPECT was performed after inhalation of 99mTc-Technegas, reaching 30 MBq in the lungs; perfusion was performed after intravenous administration of 60–120 MBq of 99mTc-MAA.The absorbed doses (mGy) to lungs and breast from CTPA were estimated using the “ImPACT CT Patient Dosimetry Calculator”. The embryo/fetus dose was estimated for different gestational stages (0–7, 8–12, 13–25 and 26–40 weeks) using the web based calculation tool “COnceptus Dose Estimation” (CODE).Doses to organs and embryo/fetus from V/P-SPECT were estimated based on published dose data normalized to administered activity (mGy/MBq).ResultsEmbryo/fetus absorbed doses are similar for CTPA and V/P-SPECT and bellow 1 mGy. The calculated dose to the lungs (breast) was 1.3–10.6 (27–136) times higher from CTPA when compared with V/P-SPECT.ConclusionFor the diagnosis of PE in women, if both imaging modalities are available, it is recommended to proceed with V/P-SPECT rather than CTPA due to the considerably lower radiation dose to the breast.     

Computational assessment of model-based wave separation using a database of virtual subjects

The quantification of arterial wave reflection is an important area of interest in arterial pulse wave analysis. It can be achieved by wave separation analysis (WSA) if both the aortic pressure waveform and the aortic flow waveform are known. For better applicability, several mathematical models have been established to estimate aortic flow solely based on pressure waveforms. The aim of this study is to investigate and verify the model-based wave separation of the ARCSolver method on virtual pulse wave measurements.The study is based on an open access virtual database generated via simulations. Seven cardiac and arterial parameters were varied within physiological healthy ranges, leading to a total of 3325 virtual healthy subjects. For assessing the model-based ARCSolver method computationally, this method was used to perform WSA based on the aortic root pressure waveforms of the virtual patients. As a reference, the values of WSA using both the pressure and flow waveforms provided by the virtual database were taken.The investigated parameters showed a good overall agreement between the model-based method and the reference. Mean differences and standard deviations were −0.05 ± 0.02 AU for characteristic impedance, −3.93 ± 1.79 mmHg for forward pressure amplitude, 1.37 ± 1.56 mmHg for backward pressure amplitude and 12.42 ± 4.88% for reflection magnitude.The results indicate that the mathematical blood flow model of the ARCSolver method is a feasible surrogate for a measured flow waveform and provides a reasonable way to assess arterial wave reflection non-invasively in healthy subjects.     

Dosimetric impact of 4DCT artifact in carbon-ion scanning beam treatment: Worst case analysis in lung and liver treatments

IntroductionWe evaluated the impact of 4DCT artifacts on carbon-ion pencil beam scanning dose distributions in lung and liver treatment.Methods & materials4DCT was performed in 20 liver and lung patients using area-detector CT (original 4DCT). 4DCT acquisition by multi-detector row CT was simulated using original 4DCT by selecting other phases randomly (plus/minus 20% phases). Since tumor position can move over the respiratory range in original 4DCT, mid-exhalation was set as reference phase. Total prescribed dose of 60 Gy (RBE) was delivered to the clinical target volume (CTV). Reference dose distribution was calculated with the original CT, and actual dose distributions were calculated with treatment planning parameters optimized using the simulated CT (simulated dose). Dose distribution was calculated by substituting these parameters into the original CT.ResultsFor liver cases, CTV-D95 and CTV-Dmin values for the reference dose were 97.6 ± 0.5% and 89.8 ± 0.6% of prescribed dose, respectively. Values for the simulated dose were significantly degraded, to 88.6 ± 14.0% and 46.3 ± 26.7%, respectively. Dose assessment results for lung cases were 84.8 ± 12.8% and 58.0 ± 24.5% for the simulated dose, showing significant degradation over the reference dose of 95.1 ± 1.5% and 87.0 ± 2.2%, respectively.Conclusions4DCT image quality should be closely checked to minimize degradation of dose conformation due to 4DCT artifacts. Medical staff should pay particular attention to checking the quality of 4DCT images as a function of respiratory phase, because it is difficult to recognize 4DCT artifact on a single phase in some cases     

La perfusion pulmonaire en morphoTEMP dans le diagnostic de l’embolie pulmonaire : comparaison à la scintigraphie pulmonaire planaire de ventilation/perfusion

The aim of this study is to assess a new tool for the diagnosis of acute pulmonary embolism (PE): single-photon emission computed tomography lung perfusion imaging associated with unenhanced computed tomography (SPECT/CT) compared to planar ventilation-perfusion (VQ) lung scintigraphy.MethodsOne hundred and three patients with suspected acute PE underwent VQ scintigraphy (two scans were uninterpretable) followed by perfusion SPECT/CT. The two types of images were analysed separately: (1) according to the modified PIOPED scintigraphic criteria for VQ lung scan and (2) with regard to SPECT/CT mismatches suggestive acute PE (segmental perfusion defects detected on SPECT images not matched with CT abnormalities).ResultsOn average, the number of segmental perfusion defects per patient was higher with SPECT/CT than with planar scintigraphy (4.3 ± 3.6 versus 2.8 ± 2.6; p < 0.001). A mismatch was found with SPECT-CT in 0% (0/18) of normal scintigraphy, and 8% (3/39) for low, 32% (8/25) for intermediate and 74% (14/19) for high probabilities of PE at scintigraphy. The presence of a SPECT/CT mismatch was also associated with higher pretest probability of acute PE (p = 0.001), even for the 25 patients in the intermediate-probability subgroup (p = 0.02). Finally, a SPECT/CT match was found in 29 patients that was not suggestive of acute PE due to the presence, in areas with perfusion defects on SPECT images, of the following CT abnormalities: hypodensity and/or emphysema (71%), condensation or atelectasis (38%), pleural disease (7%), extrapulmonary structure (14%) and/or bronchial obstruction (7%).ConclusionIn patients with suspected acute PE, the results obtained with pulmonary SPECT/CT images are consistent with those obtained with VQ scintigraphy and the pretest probability of PE. Further studies comparing SPECT/CT imaging with angiographic techniques are now required to evaluate more specifically the diagnostic value of this new tool.     

Modification de la biodistribution non tumorale du 18FMISO,un traceur d’hypoxie,chez les patients traités par sunitinib pour cancer du rein métastatique

ObjectiveThe purpose of the study was to find the potential impact of the sunitinib on the captation of a tracer of the hypoxia, ¹⁸F-FMISO, on non tumoral tissues.Population and methodsIt was about a multicentric prospective study on 43 patients with advanced or metastatic renal cancer, treated with Sunitinib. ¹⁸F-FMISO PET/CT scan was performed before treatment, followed with a second PET/CT scan after 4 weeks of treatment with sunitinib.ResultsWe have shown a significant increase of FMISO captation under sunitinib in the lungs (p < 0.02) and the liver (p < 0.001). We have also found a significant increase of FMISO captation under antiangiogenic (p < 0.02) of the arterial wall partially calcified among 23/37 patients reached of atherosclerosis, without notable cardiovascular events in the follow-up of these patients. On the other hand, we highlighted a significant reduction of FMISO captation in arthrosic lesions (p < 0.05).Conclusion¹⁸F-FMISO PET/CT scan could be a good indicator of the potential toxicities of sunitinib, in particular the pulmonary, hepatic and cardiovascular side effects. It also shows the potential interest of antiangiogenic in inflammatory rheumatic diseases.     

Voxel-by-voxel correlation between radiologically radiation induced lung injury and dose after image-guided,intensity modulated radiotherapy for lung tumors

PurposeTo correlate radiation dose to the risk of severe radiologically-evident radiation-induced lung injury (RRLI) using voxel-by-voxel analysis of the follow-up computed tomography (CT) of patients treated for lung cancer with hypofractionated helical Tomotherapy.Methods and materialsThe follow-up CT scans from 32 lung cancer patients treated with various regimens (5, 8, and 25 fractions) were registered to pre-treatment CT using deformable image registration (DIR). The change in density was calculated for each voxel within the combined lungs minus the planning target volume (PTV). Parameters of a Probit formula were derived by fitting the occurrences of changes of density in voxels greater than 0.361 g cm⁻³ to the radiation dose. The model’s predictive capability was assessed using the area under receiver operating characteristic curve (AUC), the Kolmogorov-Smirnov test for goodness-of-fit, and the permutation test (P_test).ResultsThe best-fit parameters for prediction of RRLI 6 months post RT were D₅₀ of 73.0 (95% CI 59.2.4–85.3.7) Gy, and m of 0.41 (0.39–0.46) for hypofractionated (5 and 8 fractions) and D₅₀ of 96.8 (76.9–123.9) Gy, and m of 0.36 (0.34–0.39) for 25 fractions RT. According to the goodness-of-fit test the null hypothesis of modeled and observed occurrence of RRLI coming from the same distribution could not be rejected. The AUC was 0.581 (0.575–0.583) for fractionated and 0.579 (0.577–0.581) for hypofractionated patients. The predictive models had AUC>upper 95% band of the P_test.ConclusionsThe correlation of voxel-by-voxel density increase with dose can be used as a support tool for differential diagnosis of tumor from benign changes in the follow-up of lung IMRT patients.     

Problemas clínicos en micología médica: problema número 46

A 49 year old-man, without known previous diseases, who suffered an acute lung infection, is presented. He was a smoker and belonged to a high socioeconomic class. He suddenly presented high fever, dry cough and legs’ pain. Thorax X-ray and CT scan showed two excavated pneumonic infiltrates in the lower part of the right lung. He was treated with antibacterial antibiotics without clinical response. A transparietal fine needle lung biopsy was performed and the histopathology and cytological studies revealed an epithelioid granuloma with capsulated yeasts. Cryptococcus neoformans antigenemia was positive 1/128, and brain MR, as well as CSF studies, allowed to rule out a central nervous system compromise. The patient was successfully treated with itraconazole by oral route at a daily dose of 400 mg during 6 months. Post-treatment thorax CT scan showed a thin walled lung cavity as a sequela.     

No diagnostic impact of routinely use of respiratory gating to characterize lung nodules with 18F-FDG PET/CT

Purpose

To evaluate diagnostic impact of routinely use of respiratory gated (RG) ¹⁸FDG PET/CT to distinguish benign and malignant lung nodules.

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 acetazolamide on cytokines in rats exposed to high altitude

Acute mountain sickness (AMS) is a dangerous hypoxic illness that can affect humans who rapidly reach a high altitude above 2500 m. In the study, we investigated the changes of cytokines induced by plateau, and the acetazolamide (ACZ) influenced the cytokines in rats exposed to high altitude. Wistar rats were divided into low altitude (Control), high altitude (HA), and high altitude + ACZ (22.33 mg/kg, Bid) (HA + ACZ) group. The rats were acute exposed to high altitude at 4300 m for 3 days. The HA + ACZ group were given ACZ by intragastric administration. The placebo was equal volume saline. The results showed that hypoxia caused the heart, liver and lung damage, compared with the control group. Supplementation with ACZ significantly alleviated hypoxia-caused damage to the main organs. Compared with the HA group, the biochemical and blood gas indicators of the HA + ACZ group showed no difference, while some cytokines have significantly changed, such as activin A, intercellular adhesion molecule-1 (ICAM-1, CD54), interleukin-1α,2 (IL-1α,2), l-selectin, monocyte chemotactic factor (MCP-1), CC chemokines (MIP-3α) and tissue inhibitor of matrix metalloproteinase 1 (TIMP-1). Then, the significant difference pro-inflammatory cytokines in protein array were chosen for further research. The protein and mRNA content of pro-inflammatory cytokines MCP-1, interleukin-1β (IL-1β), tumor necrosis factor (TNF-α), interferon-γ (IFN-γ) in rat lung were detected. The results demonstrated that the high altitude affected the body’s physiological and biochemical parameters, but, ACZ did not change those parameters of the hypoxia rats. This study found that ACZ could decrease the content of pro-inflammatory cytokines, such as MCP-1, IL-1β, TNF-α and IFN-γ in rat lungs, and, the lung injury in the HA + ACZ group reduced. The mechanism that ACZ protected hypoxia rats might be related to changes in cytokine content. The reducing of the pro-inflammatory cytokines in rat lung might be other reason to explain ACZ against the acute mountain sickness.     

Vitamin A (retinol) downregulates the receptor for advanced glycation endproducts (RAGE) by oxidant-dependent activation of p38 MAPK and NF-kB in human lung cancer A549 cells

As an essential component of the diet, retinol supplementation is often considered harmless and its application is poorly controlled. However, recent works demonstrated that retinol may induce a wide array of deleterious effects, especially when doses used are elevated. Controlled clinical trials have demonstrated that retinol supplementation increased the incidence of lung cancer and mortality in smokers. Experimental works in cell cultures and animal models showed that retinol may induce free radical production, oxidative stress and extensive biomolecular damage. Here, we evaluated the effect of retinol on the regulation of the receptor for advanced glycation end-products (RAGE) in the human lung cancer cell line A549. RAGE is constitutively expressed in lungs and was observed to be down-regulated in lung cancer patients. A549 cells were treated with retinol doses reported as physiologic (2 μM) or therapeutic (5, 10 or 20 μM). Retinol at 10 and 20 μM increased free radical production, oxidative damage and antioxidant enzyme activity in A549 cells. These doses also downregulated RAGE expression. Antioxidant co-treatment with Trolox®, a hydrophilic analog of α-tocopherol, reversed the effects of retinol on oxidative parameters and RAGE downregulation. The effect of retinol on RAGE was mediated by p38 MAPK activation, as blockade of p38 with PD169316 (10 μM), SB203580 (10 μM) or siRNA to either p38α (MAPK14) or p38β (MAPK11) reversed the effect of retinol on RAGE. Trolox also inhibited p38 phosphorylation, indicating that retinol induced a redox-dependent activation of this MAPK. Besides, we observed that NF-kB acted as a downstream effector of p38 in RAGE downregulation by retinol, as NF-kB inhibition by SN50 (100 μg/mL) and siRNA to p65 blocked the effect of retinol on RAGE, and p38 inhibitors reversed NF-kB activation. Taken together, our results indicate a pro-oxidant effect of retinol on A549 cells, and suggest that modulation of RAGE expression by retinol is mediated by the redox-dependent activation of p38/NF-kB signaling pathway.     

Les métastases pulmonaires micronodulaires de type miliaire dans le cancer thyroïdien bien différencié (médullaires exclus) à propos de dix cas

Thyroid cancer is relatively a rare cancer; about 1% from all cancers; between 10 and 15% of patients with differentiated thyroid cancer develop micro or macronodular pulmonary metastases. In this study we examined the characteristics and evolution after treatment of 10 patients with micronodular or miliary metastases of well-differentiated thyroid carcinoma. Total body scintigraphy with 131 iodine, chest X-ray or CT scan, and thyroglobulin assay were performed for all patients. The treatment was iodine 131 (3, 7 GBq), therapeutic 131 iodine scan was done for all patients seven days after the 131 administration. The effect of 131 iodine treatment was evaluated by means of changes in the number and size of lung metastases on the total body scintigraphy with 131 iodine and by serum thyroglobulin levels six months after 131 iodine ablation, they all received L-thyroxin (2,4 μg/kg/j). The minimum duration of follow-up was 12 months. There were six females and four males within a range of 13–70 years old. Eight had papillary and two follicular thyroid cancer. These 10 patients benefited 131 iodine therapy. The effect of 131 iodine treatment and the prognostic values of the following variables were examined: age at the time of 131 iodine, treatment and histological findings. The miliary was rarely diagnosed on the initial investigation, only in two cases by 131 iodine scan after surgery, two cases by chest X-ray, and two cases by CT scan, the initial thyroglobulin levels was very high in seven cases, between 10 and 40 ng/ml in one case and less than 10 ng/ml in two cases. These results indicate that age, 131 iodine uptake, histological findings and the presence of other metastases are important factors in predicting the effects of 131 treatment for pulmonary metastases of well-differentiated thyroid carcinoma. Among all the variables studied, the best prognosis for survival was demonstrated by increased 131 uptake in pulmonary metastases and by early diagnosis during post surgery 131 iodine scanning of radiologicaly inapparent metastases.     

Heart position variability during voluntary moderate deep inspiration breath-hold radiotherapy for breast cancer determined by repeat CBCT scans

Voluntary moderate deep inspiration breath hold (vmDIBH) in left-sided breast cancer radiotherapy reduces cardiac dose. The aim of this study was to investigate heart position variability in vmDIBH using CBCT and to compare this variability with differences in heart position between vmDIBH and free breathing (FB).For 50 patients initial heart position with respect to the field edge (HP-FE) was measured on a vmDIBH planning CT scan. Breath-hold was monitored using an in-house developed vertical plastic stick. On pre-treatment CBCT scans, heart position variability with respect to the field edge (Δ_HP-FE) was measured, reflecting heart position variability when using an offline correction protocol. After registering the CBCT scan to the planning CT, heart position variability with respect to the chest wall (Δ_HP-CW) was measured, reflecting heart position variability when using an online correction protocol. As a control group, vmDIBH and FB computed tomography (CT) scans were acquired for 30 patients and registering both scans on the chest wall.For 34 out of 50 patients, the average HP-FE and HP-CW increased over the treatment course in comparison to the planning CT. Averaged over all patients and all treatment fractions, the Δ_HP-FE and the Δ_HP-CW was 0.8 ± 4.2 mm (range −9.4–+10.6 mm) and 1.0 ± 4.4 mm (range −8.3–+10.4 mm) respectively. The average gain in heart to chest wall distance was 11.8 ± 4.6 mm when using vmDIBH instead of FB. In conclusion, substantial variability in heart position using vmDIBH was observed during the treatment course.     

Evaluation of mesh- and binary-based contour propagation methods in 4D thoracic radiotherapy treatments using patient 4D CT images

Based on four dimensional (4D) computed tomography (CT) images, mesh- and binary-based contour propagation algorithms for 4D thoracic radiotherapy treatments were evaluated. Gross tumor volumes (GTVs), lungs, hearts and spinal cords on the CT images at the end-exhale and end-inhale phases for six patients were delineated by the physician. All volumes of interest (VOIs) were automatically propagated from the end-exhale phase to the end-inhale phase using two propagation methods. The propagated VOIs were quantitatively compared with the VOIs contoured at the end-inhale phase by the physician using Dice Similarity Coefficient (DSC), Mean Slicewise Hausdorff Distance (MSHD), Center Of Mass (COM) displacement and volume difference. A two-sided Student’s t test was implemented to examine the significance of the differences between the results obtained from the two algorithms. For GTVs, statistically significant differences between the two algorithms were not observed. For all the other VOIs, the mesh-based method showed higher mean DSCs for the heart, left lung, right lung and spinal cord, lower mean MSHD for the spinal cord, lower mean COM displacement for the heart, and lower mean volume differences for the left lung, right lung and spinal cord with statistically significant differences than the binary-based method. The running time for propagation was approximately 3 s and 3 min for the mesh- and binary-based methods, respectively. Collectively, the mesh-based algorithm provides superiorities in running time and reliability for contour propagation in 4D radiotherapy.     

Validité de la somme angulaire comme technique d’extraction d’images planaires à partir de données tomoscintigraphiques pulmonaires de ventilation-perfusion

The aim of our study was to assess the concordance between the results of angular summed images obtained from lung SPECT data versus true planar images in the diagnosis of pulmonary embolism. One hundred and ten patients suspected of pulmonary embolism included in a prospective study underwent a planar lung scan and a lung SPECT. Planar images were extracted from SPECT data using an angular summing technique. Both modalities were reviewed according to revised Pioped criteria by two nuclear medicine physicians. Concordance between modalities and observers was compared with a weighted kappa test. A good degree of agreement between the two modalities (κ = 0.696) were found. Interobserver degree of agreement was similar in planar images (κ = 0.919) and in angular summed images (κ = 0.903). These results suggest that angular sum images from SPECT data are usable and concordant with ventilation perfusion planar images.     

Problème diagnostique posé par une lésion hépatique hypermétabolique en TEP à la fluorocholine (18F) : à propos d’un cas

IntroductionWe report a case of atypical fluorocholine (18F) PET/CT hypermetabolic hepatic lesion discovered during the staging of a prostate carcinoma.Case reportBecause of elevated PSA serum level, the patient had prostate biopsies which elicited an adenocarcinoma with a Gleason score of 8 (4 + 4). Pelvic MRI did not display any extracapsular disease extension. The PET/CT scan demonstrated a prostatic focal uptake and a liver increased uptake area matching with a segment VII hepatic nodule measuring 25 mm within a fatty liver, which was hypometabolic on the PET scan and hypodense on the CT scan. The liver ultrasound study reported the lesion as a focal spared area of healthy liver tissue within steatosis, whereas MRI diagnostic conclusion was inflammatory hepatocellular adenoma. When asking the patient, it appeared that the hepatic nodule had been known for 7 years, its size was unchanged, and, from previous radiologic imaging, it had been considered as an adenoma. However, there was no histological proof.DiscussionIn the interpretation of the PET/CT scan findings, we excluded a hepatocellular carcinoma and a prostate metastasis due to the long period of time during which the nodule had been followed up without significant change. We thought that focal nodular hyperplasia, which is fluorocholine avid, was the most likely diagnosis, knowing that hepatocellular adenomas, including the inflammatory type, have not been reported to display increased fluorocholine uptake. We noticed that the patient's fatty liver uptake was low, which could have accounted for a falsely increased uptake by the nodule. But, similarly to other authors, we could not find any relationship between CT density and fluorocholine uptake.ConclusionThis case shows a discrepancy between the radiologic and nuclear medicine findings. However, this hepatic nodule is likely to be benign because of the lesion characteristics and the patient medical history.     

Nanoparticle-aided external beam radiotherapy leveraging the Čerenkov effect

This study investigates the feasibility of exploiting the Čerenkov radiation (CR) present during external beam radiotherapy (EBRT) for significant therapeutic gain, using titanium dioxide (titania) nanoparticles (NPs) delivered via newly designed radiotherapy biomaterials. Using Monte Carlo radiation transport simulations, we calculated the total CR yield inside a tumor volume during EBRT compared to that of the radionuclides. We also considered a novel approach for intratumoral titania delivery using radiotherapy biomaterials (e.g. fiducials) loaded with NPs. The intratumoral distribution/diffusion of titania released from the fiducials was calculated. To confirm the CR induced enhancement in EBRT experimentally, we used 6 MV radiation to irradiate human lung cancer cells with or without titania NPs and performed clonogenic assays. For a radiotherapy biomaterial loaded with 20 μg/g of 2-nm titania NPs, at least 1 μg/g could be delivered throughout a tumor sub-volume of 2-cm diameter after 14 days. This concentration level could inflict substantial damage to cancer cells during EBRT. The Monte Carlo results showed the CR yield by 6 MV radiation was higher than by the radionuclides of interest and hence greater damage might be obtained during EBRT. In vitro study showed significant enhancement with 6 MV radiation and titania NPs. These preliminary findings demonstrate a potential new approach that can be used to take advantage of the CR present during megavoltage EBRT to boost damage to cancer cells. The results provide significant impetus for further experimental studies towards the development of nanoparticle-aided EBRT powered by the Čerenkov effect.