Physiological 68Ga-PSMA-11 Uptake in Dural Venous Sinuses.

ABSTRACT: We describe hitherto unreported physiological low-grade 68Ga-PSMA-11 uptake in dural sinuses of patients who underwent 68Ga-PSMA-11 PET/CT for evaluation of prostate carcinoma. A strong positive correlation was found between SUVmax of tracer uptake in dural sinuses and SUVmax of blood pool activity in superior vena cava. Low-grade 68Ga-PSMA-11 uptake seen in dural sinuses is physiological and is most likely result of venous blood pool activity. Such uptake should not be interpreted as pathological. Knowledge of such physiological uptake is essential for optimal interpretation of PSMA PET/CT images and differentiating physiological versus pathological uptake.

AuntMinnie Fluorodeoxyglucose Positron Emission Tomography-Computed Tomography Leads to Diagnosis of Immunoglobulin G4-Related Disease.

A 61-year-old male underwent fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET-CT) for evaluation of fever and weight loss with clinical suspicion of occult malignancy or tuberculosis. The scan showed hypermetabolism in bilateral submandibular salivary glands, biliary radicles, pancreas, bilateral kidneys, prostate, and multiple lymph nodes. Based on the concomitant involvement of these sites, suspicion of immunoglobulin G4 (IgG4)-related disease was raised in PET-CT report. Further evaluation with serum IgG4 levels and histopathology of the submandibular salivary gland confirmed the diagnosis of IgG4-related disease. The ability of FDG PET-CT to evaluate the whole-body status of disease played a crucial role in this case.

Penile Metastasis from Renal Cell Carcinoma: Diagnosis and Posttreatment Response Seen on Fluorodeoxyglucose Positron Emission Tomography-Computed Tomography.

We present fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET-CT) findings in an extremely rare case of penile metastasis from renal cell carcinoma. A 66-year-old male, a known case of renal cell carcinoma, underwent FDG PET-CT. The scan showed metabolically active cervical lymph nodes, lytic skeletal lesions, deposit in the left adrenal gland, and nodules in the bilateral lungs, indicating metastatic disease. In addition, a hypermetabolic lesion was seen in the corpus cavernosum of the shaft of the penis, suggestive of penile metastasis. Follow-up PET-CT after tyrosine kinase inhibitor therapy showed reduction in size and metabolic activity of all previously seen lesions including penile lesion, suggestive of favorable response to therapy.

Titanium Dioxide Nanotube Arrays for Cardiovascular Stent Applications.

Efficient stent implantation among others depends on avoiding the aggregation of platelets in the blood vessels and appropriate proliferation of endothelial cells and controlled proliferation of smooth muscle cells, which reduces the development of pathology, such as neointimal hyperplasia, thrombosis, and restenosis. The current article provides an elegant solution for prevention of platelet and smooth muscle cell adhesion and activation on stent surfaces while obtaining surface conditions to support the growth of human coronary artery endothelial cells. This was achieved by surface nanostructuring and chemical activation of the surface. Specific nanotopographies of titanium were obtained by electrochemical anodization, while appropriate chemical properties were attained by treatment of titanium oxide nanotubes by highly reactive oxygen plasma. Surface properties were studied by scanning electron microscopy, atomic force microscopy, and X-ray photoelectron spectroscopy. Wettability was evaluated by measuring the water contact angle. The influence of nanostructured morphology and plasma modification on in vitro biological response with human coronary artery endothelia and smooth muscle cells as well as whole blood was studied. Our results show that a combination of nanostructuring and plasma modification of the surfaces is an effective way to achieve desired biological responses necessary for implantable materials such as stents.

The Great Mimicker-Tuberculosis Involving Prostate and Vertebrae Posing as Metastatic Prostate Carcinoma on FDG PET/CT.

A 65-year-old man underwent FDG PET/CT for evaluation of vertebral lesions, radiologically suspected to be metastases. The scan showed hypermetabolism in D8 to D9 vertebrae, retroperitoneal lymph nodes, and both the lobes of prostate. Transrectal ultrasound-guided biopsy of prostate was performed with suspicion of prostate malignancy. The biopsy revealed caseating granulomatous lesions in prostate suggestive of tuberculosis. Post antitubercular treatment patient showed excellent clinical response. Possibility of infective pathologies mimicking malignancy should be kept in mind while evaluating hypermetabolic foci seen on PET/CT. Although rare, tuberculosis of prostate needs consideration in differential diagnosis of FDG-avid foci seen in prostate.

68Ga-Prostate-Specific Membrane Antigen PET/CT Findings in Extra-axial Metastasis From Prostate Carcinoma.

A 67-year-old man with no previous history of malignancy presented with trigeminal neuralgia. MRI of the brain revealed extra-axial lesion along right trigeminal nerve suggestive of neuroma. On histopathology, the lesion was found to be metastasis from adenocarcinoma prostate. Patient underwent Ga-prostate-specific membrane antigen PET/CT for assessing the whole-body status of the disease, which revealed primary prostate lesion, metastatic bone lesions, and extra-axial lesion along the right trigeminal nerve. Extra-axial, intracranial metastasis from prostate carcinoma is an uncommon phenomenon. We describe Ga-prostate-specific membrane antigen PET/CT findings in an exceedingly rare case of extra-axial metastatic lesion from prostate carcinoma.

Interaction of nanostructured TiO2 biointerfaces with stem cells and biofilm-forming bacteria.

Nanostructured TiO2 nanotubes (NTs) of diameters from 15 to 100nm were fabricated by an electrochemical anodization process. Biofilm-positive strains of Bacillus cereus and Pseudomonas aeruginosa behaved similarly on all TiO2 NTs as well as on native titanium (Ti) foil. The adhesion and growth of mesenchymal stem cells (MSc), embryonic stem cells (ESc), and pure cardiomyocytes derived from ESc exhibited significant differences. MSc as well as ESc were, in contrast to cardiomyocytes, able to adhere, and grow on TiO2 NTs. A correlation between NTs diameter and cell behaviour was however observed in the case of MSc and ESc. MSc were not in a physiological state in the case of 100nm TiO2 NTs, while ESc were not able to grow on 15nm TiO2 NTs. It can be stated that these differences can be assigned to different diameters of the NTs but not to the chemistry of the surface. This is the first study describing the comprehensive behaviour of both eukaryotic and prokaryotic cells on TiO2 NTs. On the basis of obtained results, it can be concluded that new generation of medical devices providing selective cell behaviour can be fabricated by optimizing the nanoscale morphology of TiO2.

Coexistent Superscan and Lincoln Sign on Bone Scintigraphy.

A 70-year-old man underwent Tc-methylene diphosphonate scintigraphy for staging of adenocarcinoma prostate. Scintigraphy revealed diffuse increased tracer uptake in skeletal system along with faint renal visualization, a pattern compatible with metastatic superscan. The scintigraphy also revealed increased radiotracer uptake in the body of the mandible-Lincoln sign or black beard sign. Radiological imaging revealed sclerotic lesions throughout the skeleton including the mandible, confirming widespread skeletal metastases. Lincoln sign is previously described in monostotic Paget disease of the mandible and in contiguous spread of oral malignancy. We describe this pattern in distant metastatic involvement from carcinoma prostate with coexistent superscan pattern.

Protein interactions with layers of TiO2 nanotube and nanopore arrays: Morphology and surface charge influence.

In the present work we investigate the key factors involved in the interaction of small-sized charged proteins with TiO2 nanostructures, i.e. albumin (negatively charged), histone (positively charged). We examine anodic nanotubes with specific morphology (simultaneous control over diameter and length, e.g. diameter - 15, 50 or 100nm, length - 250nm up to 10µm) and nanopores. The nanostructures surface area has a direct influence on the amount of bound protein, nonetheless the protein physical properties as electric charge and size (in relation to nanotopography and biomaterial's electric charge) are crucial too. The highest quantity of adsorbed protein is registered for histone, for 100nm diameter nanotubes (10µm length) while higher values are registered for 15nm diameter nanotubes when normalizing protein adsorption to nanostructures' surface unit area (evaluated from dye desorption measurements) - consistent with theoretical considerations. The proteins presence on the nanostructures is evaluated by XPS and ToF-SIMS; additionally, we qualitatively assess their presence along the nanostructures length by ToF-SIMS depth profiles, with decreasing concentration towards the bottom. STATEMENT OF SIGNIFICANCE: Surface nanostructuring of titanium biomedical devices with TiO2 nanotubes was shown to significantly influence the adhesion, proliferation and differentiation of mesenchymal stem cells (and other cells too). A high level of control over the nanoscale topography and over the surface area of such 1D nanostructures enables a direct influence on protein adhesion. Herein, we investigate and show how the nanostructure morphology (nanotube diameter and length) influences the interactions with small-sized charged proteins, using as model proteins bovine serum albumin (negatively charged) and histone (positively charged). We show that the protein charge strongly influences their adhesion to the TiO2 nanostructures. Protein adhesion is quantified by ELISA measurements and determination of the nanostructures' total surface area. We use a quantitative surface charge model to describe charge interactions and obtain an increased magnitude of the surface charge density at the top edges of the nanotubes. In addition, we track the proteins presence on and inside the nanostructures. We believe that these aspects are crucial for applications where the incorporation of active molecules such as proteins, drugs, growth factors, etc., into nanotubes is desired.

Electrokinetic Properties of TiO2 Nanotubular Surfaces.

Surface charge is one of the most significant properties for the characterisation of a biomaterial, being a key parameter in the interaction of the body implant with the surrounding living tissues. The present study concerns the systematic assessment of the surface charge of electrochemically anodized TiO2 nanotubular surfaces, proposed as coating material for Ti body implants. Biologically relevant electrolytes (NaCl, PBS, cell medium) were chosen to simulate the physiological conditions. The measurements were accomplished as titration curves at low electrolytic concentration (10(-3) M) and as single points at fixed pH but at various electrolytic concentrations (up to 0.1 M). The results showed that all the surfaces were negatively charged at physiological pH. However, the zeta potential values were dependent on the electrolytic conditions (electrolyte ion concentration, multivalence of the electrolyte ions, etc.) and on the surface characteristics (nanotubes top diameter, average porosity, exposed surface area, wettability, affinity to specific ions, etc.). Accordingly, various explanations were proposed to support the different experimental data among the surfaces. Theoretical model of electric double layer which takes into account the asymmetric finite size of ions in electrolyte and orientational ordering of water dipoles was modified according to our specific system in order to interpret the experimental data. Experimental results were in agreement with the theoretical predictions. Overall, our results contribute to enrich the state-of-art on the characterisation of nanostructured implant surfaces at the bio-interface, especially in case of topographically porous and rough surfaces.

Incidental Warthin Tumor on Pertechnetate Scintigraphy.

A 30-year-old woman underwent Tc-pertechnetate scintigraphy for evaluation of thyrotoxicosis. The scintigraphy revealed hypervascular thyroid gland with markedly increased trapping function in both the lobes suggesting diagnosis of Graves disease. Incidentally, a hypervascular and pertechnetate avid focus was seen along the lateral margin of the right parotid gland. Pertechnetate avidity and site of uptake suggested possibility of Warthin tumor. Clinical examination and ultrasonography revealed a well-defined lesion in the superficial lobe of the right parotid gland favoring diagnosis of benign lesion. Postsurgery specimen confirmed diagnosis of Warthin tumor.

Acute pyelonephritis resulting in intense vascular blush during dynamic renal scintigraphy.

A thirty-year-old male underwent Tc-99m diethylenetriaminepentaacetic acid renal scintigraphy for evaluation of gross hydronephrosis of left kidney. The perfusion phase revealed an intense vascular blush in left renal fossa. The uptake phase of scintigraphy revealed the absence of tracer uptake in left kidney. Contrast-enhanced computed tomography (CECT) was performed for evaluating the cause of vascular blush. CECT demonstrated features suggestive of acute pyelonephritis (APN) involving lower pole of the hydronephrotic left kidney, corresponding to the site of vascular blush seen on renal scintigraphy. The postnephrectomy specimen confirmed the diagnosis of APN suggested on CECT.

Influence of various sterilization procedures on TiO2 nanotubes used for biomedical devices.

Sterilization is the final surface treatment procedure of all implantable devices and is one of the key factors which have to be considered before implementation. Since different sterilization procedures for all implantable devices influence mechanical properties as well as biological response, the influence of different sterilization techniques on titanium nanotubes was studied. Commonly used sterilization techniques such as autoclaving, ultra-violet light sterilization, hydrogen peroxide plasma sterilization as well as the not so frequently used gaseous oxygen plasma sterilization were used. Three different nanotube diameters; 15 nm, 50 nm and 100 nm were employed to study the effects of various sterilization techniques. It was observed that autoclave sterilization resulted in destruction of nanotubular features on all three studied nanotube diameters, while UV-light and both kinds of plasma sterilization did not cause any significant morphological changes on the surfaces. Differences between the sterilization techniques employed influenced cytocompatibility, especially in the case of nanotubes with 100 nm diameter.

Binding of human coronary artery endothelial cells to plasma-treated titanium dioxide nanotubes of different diameters.

Nanoscale topography in improving vascular response in vitro was established previously on various titanium surfaces. In the present study different surface nanotopographies that is different diameters of titanium dioxide (TiO2 ) nanotubes (NTs) were fabricated by electrochemical anodization and conditioned with highly reactive gaseous oxygen plasma. The morphology of different diameter NTs was studied by scanning electron microscopy and atomic force microscopy, while changes in chemical composition on the surface before and after plasma treatment were determined by X-ray photoelectron spectroscopy. Performance of human coronary artery endothelial cells (HCAEC) on those conditioned surfaces was studied in regard to cell proliferation, released IL-6 protein and immunofluorescence microscopy (IFM). We show that HCAEC function is dependent on the diameter of the TiO2 NTs, functioning far less optimally when bound to 100 nm TiO2 NTs as compared to Ti foil, 15 nm NTs or 50 nm NTs. There were improved, morphological cell shape changes, observed with IFM, between HCAEC growing on oxygen-rich plasma-treated versus nontreated 100 nm NTs. These endothelialized conditioned Ti nanosurfaces could elucidate optimization conditions necessary for vascular implants in coronary arteries.

Adherence of oral streptococci to nanostructured titanium surfaces.

OBJECTIVES: Peri-implantitis and peri-mucositis pose a severe threat to the success of dental implants. Current research focuses on the development of surfaces that inhibit biofilm formation while not inferring with tissue integration. This study compared the adherence of two oral bacterial species, Streptococcus sanguinis and Streptococcus mutans to nanostructured titanium surfaces. METHODS: The samples included TiO2 nanotubes formed by anodization of titanium foil of 100, 50 and 15nm diameter (NT15, NT50, NT100), a nanoporous (15nm pore diameter) surface and compact TiO2 control. Adherent surviving bacteria were enumerated after 1h in an artificial saliva medium containing bovine mucin. RESULTS: Lowest numbers of adherent bacteria of both species were recovered from the original titanium foil and nanoporous surface and highest numbers from the Ti100 nanotubes. Numbers of attached S. sanguinis increased in the order (NT15

Wettability studies of topologically distinct titanium surfaces.

Biomedical implants made of titanium-based materials are expected to have certain essential features including high bone-to-implant contact and optimum osteointegration, which are often influenced by the surface topography and physicochemical properties of titanium surfaces. The surface structure in the nanoscale regime is presumed to alter/facilitate the protein binding, cell adhesion and proliferation, thereby reducing post-operative complications with increased lifespan of biomedical implants. The novelty of our TiO2 nanostructures lies mainly in the high level control over their morphology and roughness by mere compositional change and optimisation of the experimental parameters. The present work focuses on the wetting behaviour of various nanostructured titanium surfaces towards water. Kinetics of contact area of water droplet on macroscopically flat, nanoporous and nanotubular titanium surface topologies was monitored under similar evaporation conditions. The contact area of the water droplet on hydrophobic titanium planar surface (foil) was found to decrease during evaporation, whereas the contact area of the droplet on hydrophobic nanorough titanium surfaces practically remained unaffected until the complete evaporation. This demonstrates that the surface morphology and roughness at the nanoscale level substantially affect the titanium dioxide surface-water droplet interaction, opposing to previous observations for microscale structured surfaces. The difference in surface topographic nanofeatures of nanostructured titanium surfaces could be correlated not only with the time-dependency of the contact area, but also with time-dependency of the contact angle and electrochemical properties of these surfaces.

Binding of plasma proteins to titanium dioxide nanotubes with different diameters.

Titanium and titanium alloys are considered to be one of the most applicable materials in medical devices because of their suitable properties, most importantly high corrosion resistance and the specific combination of strength with biocompatibility. In order to improve the biocompatibility of titanium surfaces, the current report initially focuses on specifying the topography of titanium dioxide (TiO2) nanotubes (NTs) by electrochemical anodization. The zeta potential (ζ-potential) of NTs showed a negative value and confirmed the agreement between the measured and theoretically predicted dependence of ζ-potential on salt concentration, whereby the absolute value of ζ-potential diminished with increasing salt concentrations. We investigated binding of various plasma proteins with different sizes and charges using the bicinchoninic acid assay and immunofluorescence microscopy. Results showed effective and comparatively higher protein binding to NTs with 100 nm diameters (compared to 50 or 15 nm). We also showed a dose-dependent effect of serum amyloid A protein binding to NTs. These results and theoretical calculations of total available surface area for binding of proteins indicate that the largest surface area (also considering the NT lengths) is available for 100 nm NTs, with decreasing surface area for 50 and 15 nm NTs. These current investigations will have an impact on increasing the binding ability of biomedical devices in the body leading to increased durability of biomedical devices.

Incremental value of 18F-FDG PET/CT in therapeutic decision-making of potentially curable esophageal adenocarcinoma.

AIMS AND OBJECTIVES: The aim of the study was to estimate the incremental value of fluorine-18 fluorodeoxyglucose (F-FDG) PET/computed tomography (CT) in aiding treatment decisions in a specific cohort of patients with lower esophageal and gastroesophageal junction adenocarcinoma who were considered for potentially curative treatment on the basis of conventional imaging. MATERIALS AND METHODS: The study included patients referred for a staging F-FDG PET/CT who were considered for potentially curative treatment (neoadjuvant therapy followed by surgery or definitive chemoradiotherapy) by a multidisciplinary tumor board. The proportion of patients with M1b disease (American Joint Committee on Cancer, 6th ed.) detected on F-FDG PET/CT was calculated. The sensitivity, specificity, positive and negative predictive values, and accuracy of F-FDG PET/CT for M1b disease were calculated. PET/CT findings were verified with histopathological analysis; when it was not possible to obtain pathological confirmation, correlative imaging or follow-up imaging studies were used for validation. RESULTS: A total of 156 patients who fulfilled the inclusion criteria were analyzed. F-FDG PET/CT detected M1b disease in 25 patients (16%), changing the intent of treatment from potentially curative to palliative. In five patients, PET/CT failed to detect distant metastases. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of F-FDG PET/CT for detecting M1b disease were 83.3, 98.4, 92.5, 96.1, and 95.3%, respectively. Additional surgical procedures (hemicolectomy and polypectomy) were performed in three patients because of the detection of a second primary cancer in the colon in two patients and a colonic dysplastic polyp in one patient. CONCLUSION: In patients who are considered to be potentially curable after conventional imaging, F-FDG PET/CT can detect unsuspected sites of distant metastases (M1b) in a significant number of cases and thus contribute to the clinical decision-making process. PET/CT should be an integral part of the staging workup of patients with esophageal adenocarcinoma.

Influence of nanoparticle-membrane electrostatic interactions on membrane fluidity and bending elasticity.

The aim of this work is to investigate the effect of electrostatic interactions between the nanoparticles and the membrane lipids on altering the physical properties of the liposomal membrane such as fluidity and bending elasticity. For this purpose, we have used nanoparticles and lipids with different surface charges. Positively charged iron oxide (γ-Fe2O3) nanoparticles, neutral and negatively charged cobalt ferrite (CoFe2O4) nanoparticles were encapsulated in neutral lipid 1-stearoyl-2-oleoyl-sn-glycero-3-phosphocholine and negatively charged 1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-L-serine lipid mixture. Membrane fluidity was assessed through the anisotropy measurements using the fluorescent probe 1,6-diphenyl-1,3,5-hexatriene. Though the interaction of both the types of nanoparticles reduced the membrane fluidity, the results were more pronounced in the negatively charged liposomes encapsulated with positively charged iron oxide nanoparticles due to strong electrostatic attractions. X-ray photoelectron spectroscopy results also confirmed the presence of significant quantity of positively charged iron oxide nanoparticles in negatively charged liposomes. Through thermally induced shape fluctuation measurements of the giant liposomes, a considerable reduction in the bending elasticity modulus was observed for cobalt ferrite nanoparticles. The experimental results were supported by the simulation studies using modified Langevin-Poisson-Boltzmann model.

Interaction between dipolar lipid headgroups and charged nanoparticles mediated by water dipoles and ions.

In this work, a theoretical model describing the interaction between a positively or negatively charged nanoparticle and neutral zwitterionic lipid bilayers is presented. It is shown that in the close vicinity of the positively charged nanoparticle, the zwitterionic lipid head groups are less extended in the direction perpendicular to the membrane surface, while in the vicinity of the negatively charged nanoparticle, the headgroups are more extended.This result coincides with the calculated increase in the osmotic pressure between the zwitterionic lipid surface and positively charged nanoparticle and the decrease of osmotic pressure between the zwitterionic lipid surface and the negatively charged nanoparticle.Our theoretical predictions agree well with the experimentally determined fluidity of a lipid bilayer membrane in contact with positively or negatively charged nanoparticles. The prospective significance of the present work is mainly to contribute to better understanding of the interactions of charged nanoparticles with a zwitterionic lipid bilayer, which may be important in the efficient design of the lipid/nanoparticle nanostructures (like liposomes with encapsulated nanoparticles), which have diverse biomedical applications, including targeted therapy (drug delivery) and imaging of cancer cells.