Prospective intra-individual blinded comparison of [18F]PSMA-1007 and [68 Ga]Ga-PSMA-11 PET/CT imaging in patients with confirmed prostate cancer.

INTRODUCTION: [18F]PSMA-1007 has potential advantages over [68 Ga]Ga-PSMA-11, although limited prospective data evaluating diagnostic performance exist. The aims of this study are to describe the concordance of [18FPSMA-1007 and [68 Ga]Ga-PSMA-11 for TNM with the American Joint Committee on Cancer (AJCC) prognostic stage and assess differences in tracer uptake. METHODS: Fifty men (mean age 71.8) were imaged with [68 Ga]Ga-PSMA-11 and [18F]PSMA-1007 < 4 weeks apart. Images were independently reported according to TNM by two experienced nuclear medicine specialists blinded to the other scan and prior imaging. Discordant results were resolved by a third independent nuclear medicine specialist. Quantitative analysis of lesion uptake and physiologic tissue for each tracer was performed by one experienced reader. RESULTS: Scan indications were initial staging (n = 12), biochemical recurrence (n = 27) and metastatic disease evaluation (n = 11). Most patients had ISUP grade group 3 or higher. Median PSA value was 2.7 ng/ml (IQR 0.7-12.0), and a minority of patients (28%) were currently treated with androgen deprivation therapy. [18F]PSMA-1007 uptake was significantly higher than [68Ga]Ga-PSMA-11 in local recurrence, nodal and distant metastases and most physiologic sites (including bone) except for urinary bladder which was significantly lower. [18F]PSMA-1007 upstaged local prostate staging in 5/17 patients, local recurrence in 3/33 patients, regional nodal disease in 3/50 patients and 1 distant metastasis (bladder). [68Ga]Ga-PSMA-11 upstaged regional nodal disease in 1/50 patients and distant metastasis in one patient (right adrenal). Overall AJCC prognostic stage was concordant in 46/50 (92%) patients, with two patients upstaged for both [18F]PSMA-1007 and [68Ga]Ga-PSMA-11. [18F]PSMA-1007 had more equivocal results (one regional node; six equivocal bone lesions, one of which was subsequently confirmed metastatic) than [68Ga]Ga-PSMA-11 (one equivocal local recurrence). CONCLUSION: Overall AJCC prognostic stage was similar (92%) between [18F]PSMA-1007 and [68Ga]Ga-PSMA-11. [18F]PSMA-1007 demonstrates higher uptake within involved nodes and distant metastases and most physiologic sites except urinary bladder which aided [18F]PSMA-1007 local staging of the prostate primary/local recurrence and regional nodal disease adjacent ureters. However, [18F]PSMA-1007 liver uptake obscured a solitary right adrenal metastasis, and more equivocal bone lesions were identified. Trial registration The study was registered with Australia New Zealand Clinical Trials Registry (ACTRN12618000665235) on 24 April 2018.

Synthesis of (Hyper)Branched Monohydroxyl Alkoxysilane Oligomers toward Silanized Urethane Prepolymers.

The aim of this work was the synthesis of (hyper)branched oligomers based on trialkoxysilane in various conditions and further application of them in order to modify the urethane prepolymers. Hydroxyl-terminated trialkoxysilane was used as a monomer for homo-condensation. It was obtained by reaction of 3-aminopropyl trialkoxysilane (APTES) with ethylene carbonate (EC). The reaction was based on the attack of amine at the carbonyl carbon atom followed by ring opening of the carbonate to give a urethane (carbamate) product. The next step was the condensation via substitution of ethoxy groups on silicon atom with the terminal hydroxyalkyl groups present in the primary product with the evolution of ethanol. Accordingly, the impact of temperature and type of catalyst on process efficiency was investigated. A quantitative analysis of reaction progress and products of the conversion of EC together with ethanol evolution was conducted by means of gas chromatography, which allowed us to determine the formation of monomeric product and, indirectly, of oligomeric products. It was found that at room temperature after 24 h, the majority of the monomeric product was isolated, whereas at elevated temperature in the presence of Ti-based catalyst, further condensation of the monomer into branched oligomers was preferred, and, moreover, the application of vacuum intensified that process. The obtained products were structurally characterized by 1H and 29Si NMR, MALDI-ToF and Gel Permeation Chromatography. Finally, two different alkoxysilane products, monomeric and oligomeric, were applied for modification of urethane prepolymer, forming silanized one (SPUR). The influence of the silanizing agent on the mechanical and thermal properties of the moisture-cured products was shown before and after additional conditioning in water.

Recent Advances in the Application of ATRP in the Synthesis of Drug Delivery Systems.

Advances in atom transfer radical polymerization (ATRP) have enabled the precise design and preparation of nanostructured polymeric materials for a variety of biomedical applications. This paper briefly summarizes recent developments in the synthesis of bio-therapeutics for drug delivery based on linear and branched block copolymers and bioconjugates using ATRP, which have been tested in drug delivery systems (DDSs) over the past decade. An important trend is the rapid development of a number of smart DDSs that can release bioactive materials in response to certain external stimuli, either physical (e.g., light, ultrasound, or temperature) or chemical factors (e.g., changes in pH values and/or environmental redox potential). The use of ATRPs in the synthesis of polymeric bioconjugates containing drugs, proteins, and nucleic acids, as well as systems applied in combination therapies, has also received considerable attention.

Polymeric Materials Based on Carbon Dioxide: A Brief Review of Studies Carried Out at the Faculty of Chemistry, Warsaw University of Technology.

Carbon dioxide is an important raw material in many industrial technologies, but it is also one of the greenhouse gases that has to be effectively removed from the environment. This contribution provides a brief overview of carbon dioxide-based polymers developed in the laboratories of the Faculty of Chemistry at Warsaw University of Technology. We present some simple and versatile synthetic approaches that can be used to prepare a library of oligocarbonate diols, polycarbonates, poly(ester-carbonates), poly(ether-carbonates) and various types of polyurethanes, including the newly emerging family of environmentally friendly non-isocyanate polyurethanes. The main synthesis strategy involves the reaction of CO2 with oxiranes to form five-membered cyclic carbonates, which can be utilized as a source of carbonate bonds in polymeric materials obtained by the ester exchange reactions and/or step-growth polyaddition. We also show that cyclic carbonates are valuable starting materials in the synthesis of hyperbranched polymers and polymer networks. The properties of several CO2-based polymers are presented and their potential application as biomaterials, smart materials, and absorbers with a high CO2 capture capacity is discussed.

Dynamic Supramolecular Polymers Based on Zinc Bis(diorganophospate)s: Synthesis, Structure and Transformations in Solid State and Solutions.

The synthesis, structure and some properties of coordination polymers composed of linear zinc bis(diorganophospate)s (ZnDOPs) with a general formula of Zn[O2P(OR)2]2 (where R = CH3, C2H5, n-C4H9, or 2-ethylhexyl group) are described. Hybrid (co)polymers obtained by different procedures were characterized by means of powder XRD, DSC, SEM, TGA coupled with mass spectrometry of the evolved gases and rheological measurements, as well as FTIR and NMR techniques. The morphology, thermal transformations and solubility of ZnDOPs strongly depend on the type of organic substituent in the O2P(OR)2 ligands and the thermal history of the sample. Because of this, one can obtain highly crystalline rods, semicrystalline powders, as well as rubbery materials exhibiting a second-order transition below -50 °C. Polymeric chains formed by ZnDOPs undergo a reversible dissociation in polar organic solvents (e.g., methanol, DMSO), which allows for easy modification of their composition and physicochemical properties via a simple exchange of diorganophosphate anions. Some of the ZnDOPs were investigated as the latent curing agents for epoxides. On the basis of rheological and DSC studies, it is evident that ZnDOPs catalyze very effectively the cross-linking process within the 130-160 °C temperature range.

Influence of substituents in aryl groups on the structure, thermal transitions and electrorheological properties of zinc bis(diarylphosphate) hybrid polymers.

The structures and thermal properties of three new hybrid one-dimensional (1D) polymers based on zinc bis(diarylphosphate)s containing p-substituted phenyl rings are reported. The crystal structures of Zn[O2P(p-OC6H4NO2)2]2 (1), Zn[O2P(p-OC6H4OMe)2]2 (2) and Zn[O2P(p-OC6H4CO2Et)2]2 (3) differ from that of their unsubstituted analogue, Zn[O2P(OPh)2]2 (ZnDPhP). Compounds 1 and 3 consist of tetrahedrally coordinated zinc cations connected by double bridges of phosphate groups (2+2 bridging mode) and form polymeric chains that are packed in a distorted hexagonal lattice with six closest neighbours. In compound 2 zinc cations are linked by alternating single and triple phosphate bridges (3+1 bridging mode) and the resulting chains, having only four closest neighbors, are packed in a distorted tetragonal manner. DFT computations revealed that the 2+2 bridging mode, even at the highest energy conformation, is more stable than the 3+1 one. Simultaneous Thermal Analysis, Raman spectroscopy and powder XRD (PXRD) studies show that pyrolysis of the studied hybrid polymers begins above 260 °C, leading to a mixture of zinc condensed phosphates and carbonaceous deposits that may have electron-conducting properties. DSC and PXRD studies provide evidence that crystalline domains in 2 and 3 rearrange and/or disappear at a much lower temperature (ca. 150 °C) leading to an isotropic liquid (in the case of 3) or an amorphous solid material (in the case of 2). Electrorheological measurements indicate that 1-3 are polarized in an external electric field, and the type of electrorheological effect depends on the type of functional group attached to the phenyl ring; this feature can be utilized in designing new electrorheological devices.

New Organophilic Montmorillonites with Lactic Acid Oligomers and Other Environmentally Friendly Compounds and Their Effect on Mechanical Properties of Polylactide (PLA).

New organophilic montmorillonites with oligomers of lactic acid and other compounds such as citric acid, stearic acid, maleic anhydride, pentaerythritol and ε-caprolactone were synthesized. They were characterized by Fourier Transform Infrared Spectroscopy (FTIR), X-ray Diffraction (XRD), Thermogravimetric Analysis (TGA), Scanning Electron Microscopy (SEM), elemental analysis and swelling capacity in water. In all tested composites, an increase in the montmorillonite interlayer distance resulting from intercalation of the modifying substance in the montmorillonite was found by means of XRD. Elemental analysis and FTIR showed that all of the tested samples contained an organic segment in the montmorillonite structure. TGA studies revealed that composites modified with lactic acid oligomers, stearic acid or ε-caprolactone had the highest thermal stability. They also exhibited the lowest swelling capacity which was 2-3 times lower than that for unmodified sodium montmorillonite. Some preliminary studies on the mechanical properties of PLA/modified montmorillonite are also presented and discussed.

Effect of Electron-Beam Radiation and Other Sterilization Techniques on Structural, Mechanical and Microbiological Properties of Thermoplastic Starch Blend.

This work investigates the potential application of various sterilization methods for microorganism inactivation on the thermoplastic starch blend surface. The influence of the e-beam and UV radiation, ethanol, isopropanol and microwave autoclave on structural and packaging properties were studied. All the applied methods were successful in the inactivation of yeast and molds, however only the e-beam radiation was able to remove the bacterial microflora. The FTIR analysis revealed no significant changes in the polymer structure, nevertheless, a deterioration of the mechanical properties of the blend was observed. The least invasive method was the UV radiation which did not affect the mechanical parameters and additionally improved the barrier properties of the tested material. Moreover, it was proved that during the e-beam radiation the chain scission and cross-linking occurred. The non-irradiated and irradiated samples were subjected to the enzymatic degradation studies performed in the presence of amylase. The results indicated that irradiation accelerated the decomposition of material, which was confirmed by the measurements of weight loss, and mass of glucose and starch released to the solution in the course of biodegradation, as well as the FTIR and thermal analysis.

1D and 2D hybrid polymers based on zinc phenylphosphates: synthesis, characterization and applications in electroactive materials.

The synthesis, structure and properties of three hybrid polymers based on zinc arylphosphates are described in this study. Zinc bis(diphenylphosphate) (ZnDPhP) was obtained as needle-like crystals containing hexagonally packed, homochiral 1 ∞[Zn(DPhP)2/2] helical chains. The XRD and DSC studies revealed that upon heating, ZnDPhP undergoes a reversible thermal transition at ca. 160 °C with expansion mainly perpendicular to its c-axis. Zinc phenylphosphate hydrate (ZnMPhP-H) formed plate-like particles with an average thickness of less than 1 µm and much thinner nanolayers with a basal spacing of 15.5 Å. ZnMPhP-H was easily and reversibly dehydrated to its anhydrous form, ZnMPhP-A, which exhibited a somewhat larger basal spacing of 16.5 Å and the capacity for amine intercalation. The thermal decomposition of ZnDPhP or ZnMPhP-A began around 250 °C, resulting in the formation of solid mixtures of zinc phosphates and electron-conducting carbonaceous phases. The bulk electrical conductivities of the poly(vinylidene fluoride)-based composites containing the ZnDPhP pyrolyzates reached 0.1-0.2 S cm-1. Upon mixing with silicone oil, all the synthesized hybrid polymers formed fluids that exhibit significant negative electrorheological effects and have potential for application in electroresponsive smart materials. The application of an electric field during the crosslinking of such systems affected the viscoelastic properties of the resultant solid composites, while the cured systems showed rather small electrorheological effects.

Diagnostic performance of 18F-fluorodeoxyglucose positron emission tomography in the evaluation of glioma.

INTRODUCTION: Identifying glioma grade through imaging allows clinicians to recommend and accurately direct treatment. We sought to quantify the utility of FDG-PET/CT (18F-fluorodeoxyglucose positron emission tomography/computed tomography), alone and in combination with MRI, in identifying high-grade regions of glioma. METHODS: This is a retrospective review of patients who had an FDG-PET/CT performed as part of the workup of suspected glioma or in follow-up of known glioma. FDG-PET/CT scans were reviewed and uptake in the identifiable lesion coded as none, diffusely or focally increased. Patients also underwent gadolinium-enhanced MRI, noting regions of contrast enhancement. Sensitivity, specificity, positive and negative predictive values (PPV and NPV) were calculated for identification of high-grade histology (WHO III or IV, or metastatic disease) obtained post-FDG-PET/CT. RESULTS: Thirty-three patients had 36 FDG-PET/CT and MRI scans followed by histological confirmation (biopsy or debulking). Increased FDG uptake demonstrated a sensitivity of 59% and specificity of 79%, PPV of 81% and NPV of 55% for identification of high-grade histology. MRI demonstrated a sensitivity of 77% and specificity of 86%, PPV of 89% and NPV of 71% for identification of high-grade histology. Only 64% of MRI and FDG-PET/CT scan series were concordant. When FDG-PET/CT and MRI were concordant, a specificity of 100% and PPV of 100% was achieved, however, sensitivity was 79% and NPV was 75%. CONCLUSION: The combination of FDG-PET/CT and gadolinium-enhanced MRI demonstrated marked improvement in identifying potential high-grade disease over each modality alone. Increased FDG uptake without gadolinium enhancement rarely occurred and identified high-grade histology in a small number of patients. Due to limited sensitivity and NPV, a negative FDG-PET/CT alone, or in combination with MRI, should not guide a decision for observation where surgery would otherwise be recommended.

Thermally induced structural transformations of linear coordination polymers based on aluminum tris(diorganophosphates).

The thermal transitions of inorganic-organic hybrid polymers composed of linear aluminum tris(diorganophosphate) chains with a general formula of catena-Al[O2P(OR)2]3 (where R = C1-C8 alkyl group or phenyl moiety) have been studied by means of DSC, powder XRD, TGA and TG-QMS, as well as optical spectroscopy. DSC and XRD reveal that most of them undergo reversible structural transformations in the solid state between -100 and 200 °C caused by the changes in conformation of their organic substituents; however, a translational displacement of the rigid polymeric chains occurs only in the case of the derivative bearing long 2-ethylhexyl groups, which becomes liquid at about 140 °C. The thermal decomposition of the studied polymers begins between 200 and 265 °C depending on the type of organic substituent R decorating their aluminophospate core. TGA combined with mass spectrometry of the evolved gaseous products shows that the pyrolytic decomposition of Al[O2P(OR)2]3 proceeds either through ß-elimination of olefin (for compounds with C2-C8 aliphatic ligands), or a homolytic cleavage of the P-OR bond (for methyl and phenyl derivatives); both processes are accompanied by condensation of the newly formed POH groups and liberation of water. Powder XRD, FTIR and SEM analyses of the solid residues indicate that thermolysis of Al[O2P(OR)2]3 accompanied by olefin elimination leads to the formation of condensed aluminum phosphates, mainly aluminum cyclohexaphosphate, exhibiting porous morphology. On the other hand, thermal degradation of methyl or phenyl derivatives results in amorphous aluminophosphate residues, and the latter contains conducting carbonaceous phases.

Non-small cell lung cancer brain metastasis screening in the era of positron emission tomography-CT staging: Current practice and outcomes.

INTRODUCTION: Several clinical guidelines indicate that brain metastasis screening (BMS) should be guided by disease stage in non-small cell lung cancer (NSCLC). We estimate that screening is performed more broadly in practice, and patients undergo brain imaging at considerable cost with questionable benefit. Our aim was to quantify the use and detection rate of BMS in a contemporary cohort staged with 18 F-fluorodeoxyglucose positron emission tomography/computed tomography (PET-CT). METHODS: We conducted a retrospective review of prospectively collected data from three major lung cancer referral centres in Brisbane between January 2011 and December 2015. Patients included had a new diagnosis of NSCLC and had undergone a PET-CT to stage extra-cranial disease. BMS was defined as dedicated brain imaging with contrast-enhanced computed tomography (CE-CT) or magnetic resonance (MR), in the absence of clinically apparent neurological deficits. RESULTS: A total of 1751 eligible cases were identified and of these 718 (41%) underwent BMS. The majority had CE-CT imaging (n = 703). Asymptomatic brain metastases (BM) were detected in 18 patients (2.5%). Of these patients, 12 had concurrent non-brain metastases. Only six patients (0.8%) had BM alone. The rate of detection increased with N-stage (P = 0.02) and overall stage (P < 0.001). It was 0.5%, 1%, 1.6% and 7.3% for stage I, II, III and IV respectively. The overall screening rate increased with T-stage (P = 0.001), N-Stage (P < 0.001) and overall stage (P < 0.001). CONCLUSIONS: Non-small cell lung cancer BMS practices remain at odds with published guidelines. The low number of occult BMs detected supports the existing international recommendations. Rationalising BMS would minimise the burden on patients and the health care system.