The value of baseline 18F-sodium fluoride and 18F-choline PET activity for identifying responders to radium-223 treatment in castration-resistant prostate cancer bone metastases.

OBJECTIVES: To investigate whether baseline 18F-sodium fluoride (NaF) and 18F-choline PET activity is associated with metastatic castration-resistant prostate cancer (mCRPC) global and individual bone metastases' DWI MR imaging response to radium-223 treatment. METHODS: Thirty-six bone-only mCRPC patients were prospectively recruited from three centers. Whole-body (WB)-MRI with DWI and 18F-NaF and 18F-choline PET/CT were performed at therapy baseline and 8-week intervals. In each patient, bone disease median global (g)ADC change between baseline and follow-up was calculated. Additionally, up to five bone target lesions per patient were delineated and individual median ADC change recorded. An ADC increase > 30% defined response per-patient and per-lesion. For the same targets, baseline 18F-NaF and 18F-choline PET SUVmax were recorded. Mean SUVmax across patient targets was correlated with gADC change and lesion SUVmax with per-lesion ADC change. RESULTS: A total of 133 lesions in 36 patients (14 responders) were analyzed. 18F-NaF PET per-patient mean SUVmax was significantly higher in responders (median = 56.0 versus 38.7 in non-responders; p = 0.008), with positive correlation between SUVmax and gADC increase (rho = 0.42; p = 0.015). A 48.7 SUVmax threshold identified responders with 77% sensitivity and 75% specificity. Baseline 18F-NaF PET per-lesion SUVmax was higher in responding metastases (median = 51.6 versus 31.8 in non-responding metastases; p = 0.001), with positive correlation between baseline lesion SUVmax and ADC increase (rho = 0.39; p < 0.001). A 36.8 SUVmax threshold yielded 72% sensitivity and 63% specificity. No significant association was found between baseline 18F-choline PET SUVmax and ADC response on a per-patient (p = 0.164) or per-lesion basis (p = 0.921). CONCLUSION: 18F-NaF PET baseline SUVmax of target mCRPC bone disease showed significant association with response to radium-223 defined by ADC change. CLINICAL RELEVANCE STATEMENT: 18F-sodium fluoride PET/CT baseline maximum SUV of castration-resistant prostate cancer bone metastases could be used as a predictive biomarker for response to radium-223 therapy. KEY POINTS: • 18F-sodium fluoride PET baseline SUVmax of castration-resistant prostate cancer bone metastases showed significant association with response to radium-223. • Baseline 18F-sodium fluoride PET can improve patient selection for radium-223 therapy. • Change in whole-body DWI parameters can be used for response correlation with baseline 18F-sodium fluoride PET SUVmax in castration-resistant prostate cancer bone metastases.

Comparison of 18F-sodium fluoride PET/CT, 18F-fluorocholine PET/CT and diffusion-weighted MRI for the detection of bone metastases in recurrent prostate cancer: a cost-effectiveness analysis in France.

BACKGROUND: The diagnostic performance of 18F-sodium fluoride positron emission tomography/computed tomography (PET/CT) (NaF), 18F-fluorocholine PET/CT (FCH) and diffusion-weighted whole-body magnetic resonance imaging (DW-MRI) in detecting bone metastases in prostate cancer (PCa) patients with first biochemical recurrence (BCR) has already been published, but their cost-effectiveness in this indication have never been compared. METHODS: We performed trial-based and model-based economic evaluations. In the trial, PCa patients with first BCR after previous definitive treatment were prospectively included. Imaging readings were performed both on-site by local specialists and centrally by experts. The economic evaluation extrapolated the diagnostic performances of the imaging techniques using a combination of a decision tree and Markov model based on the natural history of PCa. The health states were non-metastatic and metastatic BCR, non-metastatic and metastatic castration-resistant prostate cancer and death. The state-transition probabilities and utilities associated with each health state were derived from the literature. Real costs were extracted from the National Cost Study of hospital costs and the social health insurance cost schedule. RESULTS: There was no significant difference in diagnostic performance among the 3 imaging modalities in detecting bone metastases. FCH was the most cost-effective imaging modality above a threshold incremental cost-effectiveness ratio of 3000€/QALY when imaging was interpreted by local specialists and 9000€/QALY when imaging was interpreted by experts. CONCLUSIONS: FCH had a better incremental effect on QALY, independent of imaging reading and should be preferred for detecting bone metastases in patients with biochemical recurrence of prostate cancer. TRIAL REGISTRATION: NCT01501630. Registered 29 December 2011.

Impact of sodium 18F-fluoride PET/CT, 18F-fluorocholine PET/CT and whole-body diffusion-weighted MRI on the management of patients with prostate cancer suspicious for metastasis: a prospective multicentre study.

PURPOSE: To compare the impact of 18F-sodium-fluoride (NaF) PET/CT, 18F-fluorocholine (FCH) PET/CT and diffusion-weighted whole-body MRI (DW-MRI) on the management of patients with prostate cancer (PCa) suspicious for distant metastasis. METHODS: Prostate cancer patients were prospectively included between December 2011 and August 2014 and benefited from these three whole-body imaging (WBI) modalities within 1 month in addition to the standard PCa workup. Management was prospectively decided by clinicians during two multidisciplinary meetings, before and after the whole-body imaging workup. Rates of induced changes of whole-body imaging modalities were compared by Cochran's Q test. RESULTS: One-hundred-one patients (27 at staging, 59 at first biochemical recurrence (BCR) and 15 at first episode of rising serum level of prostate-specific antigen during androgen-deprivation therapy) were included. The overall rate of management changes was 52%: 29% as a consequence of WBI, higher for FCH-PET/CT than for NaF-PET/CT or DW-MRI (p < 0.0001) and highest (41%) for FCH-PET/CT at BCR. Actual management was adequate in all patients but two. CONCLUSIONS: Whole-body imaging induced a change in management in approximately a third of PCa patients suspicious for metastasis. The impact rate was determined to be greatest at first BCR using FCH-PET/CT. NaF-PET/CT and DW-MRI seemed less useful in this context.

[Alveolar osteitis treatment using Holisal gel]. / Medikamentoznoe soprovozhdenie al'veolita cheliusti preparatom Kholisal.

The aim of the study was to estimate efficiency Holisal in treatment of the alveolar osteitis. 30 patients with the diagnosis of alveolar osteitis with clinics of dry socket, aged from 25 to 69 years entered a research. Patients were divided into 2 groups: in the 1st group (n=15) patients received treatment by a standard technique with the use of the iodoform gauze. In the 2nd group patients (n=15) after preliminary training used Holisal 4 times a day applying it in the socket. In both groups dynamics of clinical indicators, complaints, biochemical indicators on the 3, 5 and 10 day after the beginning of treatment were estimated. The use of Holisal for treatment of the alveolar osteitis presenting as a dry socket is effective and has advantages in comparison with a conventional technique of alveolar osteitis management.

Synthesis of Zwitterionic Pluronic Analogs.

Novel polymer amphiphiles with chemical structures designed as zwitterionic analogs of Pluronic block copolymers were prepared by controlled free radical polymerization of phosphorylcholine (PC) or choline phosphate (CP) methacrylate monomers from a difunctional poly(propylene oxide) (PPO) macroinitiator. Well-defined, water-dispersible zwitterionic triblock copolymers, or "zwitteronics", were prepared with PC content ranging from 5 to 47 mol percent and composition-independent surfactant characteristics in water, which deviate from the properties of conventional Pluronic amphiphiles. These PC-zwitteronics assembled into nanoparticles in water, with tunable sizes and critical aggregation concentrations (CACs) based on their hydrophilic-lipophilic balance (HLB). Owing to the lower critical solution temperature (LCST) miscibility of the hydrophobic PPO block in water, PC-zwitteronics exhibited thermoreversible aqueous solubility tuned by block copolymer composition. The chemical versatility of this approach was demonstrated by embedding functionality, in the form of alkyne groups, directly into the zwitterion moieties. These alkynes proved ideal for cross-linking the zwitteronic nanoparticles and for generating nanoparticle-cross-linked hydrogels using UV-initiated thiol-yne "click" chemistry.

Graphene Oxide and Lipid Membranes: Size-Dependent Interactions.

We have investigated the interaction of graphene oxide (GO) sheets with supported lipid membranes with focus on how the interaction depends on GO sheet size (three samples in the range of 90-5000 nm) and how it differs between small and large liposomes. The layer-by-layer assembly of these materials into multilamellar structures, as discovered in our previous research, is now further explored. The interaction processes were monitored by two complementary, real time, surface-sensitive analytical techniques: quartz crystal microbalance with dissipation monitoring (QCM-D, electroacoustic sensing) and indirect nanoplasmonic sensing (INPS, optical sensing). The results show that the sizes of each of the two components, graphene oxide and liposomes, are important parameters affecting the resulting multilayer structures. Spontaneous liposome rupture onto graphene oxide is obtained for large lateral dimensions of the graphene oxide sheets.

Immobilization of natural lipid biomembranes and their interactions with choline carboxylates. A nanoplasmonic sensing study.

The cell membrane is mainly composed of lipid bilayers with inserted proteins and carbohydrates. Lipid bilayers made of purified or synthetic lipids are widely used for estimating the effect of target compounds on cell membranes. However, the composition of such biomimetic membranes is much simpler than the composition of biological membranes. Interactions between compounds and simple composition biomimetic membranes might not demonstrate the effect of target compounds as precisely as membranes with compositions close to real organisms. Therefore, the aim of our study is to construct biomimetic membrane closely mimicking the state of natural membranes. Liposomes were prepared from lipids extracted from L-α-phosphatidylcholine, Escherichia coli, yeast (Saccharomyces cerevisiae) and bovine liver cells through agitation and sonication. They were immobilized onto silicon dioxide (SiO2) sensor surfaces using N-(2-hydroxyethyl)piperazine-N'-2-ethanesulfonic acid buffer with calcium chloride. The biomimetic membranes were successfully immobilized onto the SiO2 sensor surface and detected by nanoplasmonic sensing. The immobilized membranes were exposed to choline carboxylates. The membrane disruption effect was, as expected, more pronounced with increasing carbohydrate chain length of the carboxylates. The results correlated with the toxicity values determined using Vibrio fischeri bacteria. The yeast extracted lipid membranes had the strongest response to introduction of choline laurate while the bovine liver lipid extracted liposomes were the most sensitive towards the shorter choline carboxylates. This implies that the composition of the cell membrane plays a crucial role upon interaction with choline carboxylates, and underlines the necessity of testing membrane systems of different origin to obtain an overall image of such interactions.

Chitin-glucan complex - Based biopolymeric structures using biocompatible ionic liquids.

This work explores the novelty of dissolving chitin-glucan complex (CGC), from two fungal strains, Komagataella pastoris (CGCP) and Aspergillus niger (CGCKZ) (KiOnutrime-CG™), using biocompatible ionic liquids (ILs). Three cholinium-based ILs were tested, choline acetate, choline propionate and choline hexanoate. Although all tested ILs resulted in the dissolution of the co-polymer at a concentration of 5 % (w/w), distinct polymeric structures, films or gels, were obtained from CGCP and CGCKZ, respectively. CGCP films were dense, flexible and elastic, with high swelling capacity (> 200 %). The IL anion alkyl chain length influenced the polymeric structures' properties, namely, the CGCP films elongation at break and swelling degree. CGCKZ resulted in weak gels. For both polymeric structures, exposure to the ILs under the dissolution conditions caused significant changes in the co-polymers' chemical structure, namely, reduction of their glucan moiety and reduction of the degree of acetylation, thus yielding chitosan-glucan complexes (ChGC) enriched in glucosamine (53.4 ± 0.3-60.8 ± 0.3 %).

Chitosan-reinforced cellulosic bionogels: Viscoelastic and antibacterial properties.

New chitosan-reinforced cellulosic bionogels were successfully formulated with different chitosan loadings (0.25, 0.5, 0.75, and 1 wt/wt. %). These materials were developed using cholinium lysinate, a bio-ionic liquid, being an ecological alternative to conventional ionogels. The rheological properties of these materials showed that all the studied viscoelastic properties were higher (elastic moduli, G'; loss moduli, G"; and complex viscosity, η*) as the chitosan loading increased. The reinforced bionogels were physical weak gels, and the proposed mechanism of formation was by hydrogen bonds. The bionogel with 1 wt/wt. % chitosan loading exhibited the highest viscoelastic properties (for 4 Hz, G': 552 kPa, G": 99 kPa, and η*: 22 kPa·s). Regarding the antibacterial properties, these gels showed a good inhibitory capacity to S. aureus and E. coli, especially against the latter bacterium. For these reasons, these novel ecofriendly gels are promising in the pharmaceutical/medical and biosensors sectors to develop new functional materials.

[Antimicrobial activity determination of the preparations used in comprehensive treatment of patients with parodontitis].

Determination of antimicrobic activity of the preparations of Metrogyl denta, Cholisal and Solcoseryl on the complex culture of microorganisms employing the developed procedure was carried out. Degree of the antimicrobic action manifestation of each preparation was revealed.

Viscoelastic properties of physical cellulosic bionogels of cholinium lysinate.

Novel ionogels with different cellulose contents, namely, 0.5, 1, 1.5 and 2 wt%, were formulated with cholinium lysinate (ChLys), and the rheological properties were evaluated at 3 and 7 days postgelation. Because of the biobased compounds contained in these ionogels, in this work, they are denoted as bionogels. These materials have great potential to yield functional biomaterials for use in the medical/pharmacological sector. Some knowledge of how cellulose is dissolved in ChLys was necessary to formulate the bionogels. The dissolution time was studied for each bionogel, with the dissolution times being 3, 4, 4.5, and 6.5 h for 0.5, 1, 1.5, and 2% cellulose, respectively. The bionogel with a 2% cellulose load had the highest rheological properties, i.e. elastic modulus (G'), loss modulus (G″) and complex viscosity (η*), on the studied postgelation days: G' (3 days): 0.7-50 kPa, G' (7 days): 1-100 kPa, G″ (3 days): 0.1-10 kPa, and G″ (7 days): 0.2-20 kPa, η* (3 days): 0.2-200 kPa s and η* (7 days): 0.4-300 kPa s. The postgelation time is an important parameter in the formulation of bionogels, since at 3 days postgelation, the networks continued to be constituted. Regarding classification, these bionogels were weak physical gels.

Choline supported poly(ionic liquid) graft copolymers as novel delivery systems of anionic pharmaceuticals for anti-inflammatory and anti-coagulant therapy.

New type of carriers based on grafted poly(ionic liquid)s was designed for delivery of ionically attached salicylates (Sal). Choline derived ionic liquid monomeric units were successfully introduced with various content in the side chains by the controlled radical polymerization. Properly high amounts of ionic pharmaceutics in the polymer systems were achieved by the well-fitted length and grafting degree of the side chains. In aqueous solution the graft copolymers were self-assembled into the spherical superstructures with sizes up to 73 nm. Delivery studies showed "burst" release within 4 h, after that it was slower yielding ~70% of released drug within 80 h. Proposed nanocarriers supported low toxicity against human cells (NHDF and BEAS-2B), anti-inflammation activity evaluated with the use of pro-inflammatory interleukins (IL-6 and IL-8) and antibacterial activities towards E. coli. Adjustment of ionic drug content by structural parameters of graft copolymers, including grafting degree and graft length, are advantageous to tailor nanocarriers with self-assembly properties in aqueous media. Effective release process by ionic exchange and biological activity with low toxicity are promising for further development of this type of drug delivery (DDS).

[Holisal in the complex treatment of periodontal disease].

The aim of our research was to evaluate efficiency of medicine Cholisal in complex treatment of periodontitis. During the research 36 patients with periodontitis (from 18 to 36 years old) were examined and treated. The patients were divided into 3 groups according to severity of periodontitis. Each group included 12 patients. For studying the efficiency of treatment both objective and subjective data was used. In case of mild severity of disease clinical indices were: HI=2,1+/-0,75; Ghi=1,4+/-0,67; Gi=1,7+/-0,78, PI=0,8+/-0,34. In case of moderate severity of disease clinical indices were: HI=2,57+/-1,02; GHI=2,18+/-0,81; GI=1,95+/-0,8, PI=3,9+/-1,1. In case of severe disease - HI=3,9+/-1,25, GHI=2,5+/-0,8, GI=2,9+/-1,2, PI=7,8+/-1,62. Clinical study has shown that Cholisal enables successful treatment of periodontitis. It has prolonged, antiinflamatory, deodorant and analgesic effect. Our investigation revealed that xolisale can be recommended in complex treatment of periodontal disease.

A cationic conjugated polymer and graphene oxide: Application to amplified fluorescence detection of sinapine.

An amplified fluorescence strategy is described for the detection of sinapine (SP) by using a cationic conjugated polymer (PFP) and graphene oxide (GO). It is observed that the fluorescein (FAM)-labeled single-stranded DNA (FAM-DNA) is absorbed on the surface of GO if SP is absent. This causes that fluorescence resonance energy transfer (FRET) from PFP to FAM is inefficient when adding PFP into FAM-DNA/GO complex. If SP is added to FAM-DNA/GO complex, FAM-DNA is desorbed from GO surface due to the competitive binding of SP and FAM-DNA toward GO. In this case, FAM-DNA is close to PFP in the presence of PFP through strong electrostatic interaction, leading to the occurrence of efficient FRET. Based on the above phenomenon, we demonstrate a method to amplify fluorescence signal of traditional GO-based SP assay by introducing PFP. In comparison to the use of single GO, the combination of PFP with GO-based strategy displays high turn-on ratio and enhanced sensitivity with a limit of detection as low as 7.3 ng mL-1 for SP detection. Satisfactory results in practical samples are also obtained by the recovery experiments, demonstrating the potential application of cationic conjugated polymer in plant-derived small molecule.

[Superiority of 18F-FNa PET/CT for Detecting Bone Metastases in Comparison with Other Diagnostic Imaging Modalities]. / Superioridade da PET/CT com FNa-F18 na Deteção de Metástases Ósseas quando Comparada com Outros Métodos de Diagnóstico por Imagem.

INTRODUCTION: The 18F-NaF positron emission tomography/computed tomography is being considered as an excellent imaging modality for bone metastases detection. This ability was compared with other imaging techniques. MATERIAL AND METHODS: We retrospectively evaluated 114 patients who underwent 18F-NaF positron emission tomography/ computed tomography. Of these, 49 patients also had bone scintigraphy, 61 18F-FDG positron emission tomography/computed tomography and 10 18F-FCH positron emission tomography/computed tomography. We identified the technique that detected the largest number of bone metastases. For the detection of skeletal metastases with the 18F-NaF positron emission tomography/computed tomography study, the contribution of the positron emission tomography component was compared with the contribution of the computed tomography component. Cases in which 18F-NaF positron emission tomography/computed tomography and bone scintigraphy required further additional tests for diagnosis clarification were registered. RESULTS: The 18F-NaF positron emission tomography/computed tomography was superior to bone scintigraphy in 49% of the patients (p < 0.001); it was superior to 18F-FDG positron emission tomography/computed tomography in 59% of the patients (p < 0.001) and it was superior to 18F-FCH positron emission tomography/computed tomography in 40% of the patients (p < 0.001). None of the compared imaging techniques were superior to 18F-NaF positron emission tomography/computed tomography. The positron emission tomography component was superior to computed tomography in 35% of the cases (p < 0.001). Further investigation was suggested in only 3.5% of patients who underwent 18F-NaF positron emission tomography/computed tomography (45% for bone scintigraphy) (p < 0.001). DISCUSSION: As with other authors, our experience also confirms that 18F-NaF positron emission tomography/computed tomography is an excellent imaging modality for the detection of bone metastases, detecting lesions in more patients and more lesions per patient. CONCLUSION: The 18F-NaF positron emission tomography/computed tomography showed a superior ability for the detection of bone metastases when compared with bone scintigraphy, 18F-FDG positron emission tomography/computed tomography and 18F-FCH positron emission tomography/computed tomography.

Introdução: A tomografia por emissão de positrões/tomografia computorizada - FNa-F18 vem sendo considerada como uma modalidade imagiológica com vantagens na pesquisa de metastização óssea. Comparámos a sua capacidade para deteção de metástases ósseas com a de outras técnicas imagiológicas.Material e Métodos: Avaliámos retrospetivamente 114 doentes que realizaram tomografia por emissão de positrões/tomografia computorizada - FNa-F18. Destes, 49 realizaram também cintigrafia óssea, 61 tomografia por emissão de positrões/tomografia computorizada - FDG-F18 e 10 tomografia por emissão de positrões/tomografia computorizada - FCH-F18. Identificámos a técnica que detetou um maior número de metástases ósseas. Comparámos ainda a tomografia por emissão de positrões com a componente tomografia computorizada da tomografia por emissão de positrões/tomografia computorizada - FNa-F18. Registámos as situações  nas quais a tomografia por emissão de positrões/tomografia computorizada FNa-F18 e a cintigrafia óssea necessitaram de exames adicionais para esclarecimento complementar.Resultados: A tomografia por emissão de positrões/tomografia computorizada - FNa-F18 foi superior à cintigrafia óssea em 49% dos doentes (p < 0,001); foi superior à tomografia por emissão de positrões/tomografia computorizada - FDG-F18 em 59% dos doentes (p < 0,001) e foi superior à tomografia por emissão de positrões/tomografia computorizada - FCH-F18 em 40% dos doentes (p < 0,001). Nenhuma das técnicas imagiológicas avaliadas lhe foi superior. Na tomografia por emissão de positrões/tomografia computorizada -FNa-F18 a componente tomografia por emissão de positrões foi superior à tomografia computorizada em 35% dos casos (p < 0,001). Foi sugerida investigação complementar em apenas 3,5% dos doentes que realizaram tomografia por emissão de positrões/ tomografia computorizada - FNa-F18 (45% para a cintigrafia óssea) (p < 0,001).Discussão: Em conformidade com o referido por outros autores, a nossa experiência confirma que a tomografia por emissão de positrões/tomografia computorizada - FNa-F18 tem excelente desempenho na deteção de metástases ósseas, sendo capaz de identificar lesões em mais doentes, e em maior número, quando comparada com outras técnicas imagiológicas.Conclusão: A tomografia por emissão de positrões/tomografia computorizada - FNa-F18 revelou superioridade na deteção de metástases ósseas comparativamente à cintigrafia óssea, à tomografia por emissão de positrões/tomografia computorizada - FDG-F18 e à tomografia por emissão de positrões/tomografia computorizada - FCH- F18.

Ferritin-supported lipid bilayers for triggering the endothelial cell response.

Hybrid nanoassemblies of ferritin and silica-supported lipid bilayers (ferritin-SLBs) have been prepared and tested for the adhesion, spreading and proliferation of retinal microvascular endothelial cells (ECs). Lipid membranes with varying surface charge were obtained by mixing cationic 1-palmitoyl-2-oleoyl-sn-glycero-3-ethylphosphocholine (POEPC) with zwitterionic 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) at increasing POPC/POEPC ratios. The supported bilayer formation and their subsequent interaction processes with ferritin were studied at the pH of 7.4 at different protein concentrations, by using the quartz crystal microbalance with dissipation monitoring and by atomic force microscopy. Both kinetics and viscoelastic parameters of the protein-lipid membrane interface were scrutinized, as well as surface coverage. Phase-contrast optical microscopy analyses of the ferritin-SLBs substrates after their interaction with endothelial cells evidenced the highest cell adhesion (2-4h of incubation time) and proliferation (from 24h to 5 days) for the membranes of POPC/POEPC (75:25 ratio). Moreover, ferritin increased both cell adhesion and proliferation in comparison to control glass (respectively 1.5- and 1.75-fold) as well as proliferation in comparison to bare POPC/POEPC (95:5 ratio) (2 fold). Results are very promising in the goal of modulating the endothelial cell response through the interplay of viscoelastic/charge properties of the solid-supported membranes and the SLB-conditioned ferritin activity.

The quest for biocompatible phthalocyanines for molecular imaging: Photophysics, relaxometry and cytotoxicity studies.

Water soluble phthalocyanines bearing either four PEG500 or four choline substituents in the macrocyclic structure, as well as their Zn(II) and Mn(III) complexes were synthesized. The metal-free and Zn(II) complexes present relatively high fluorescence quantum yields (up to 0.30), while the Mn(III) complexes show no fluorescence as a consequence of rapid non-radiative deactivation of the Mn(III) phthalocyanine excited states through low-lying metal based or charge-transfer states. The effect of DMSO on the aggregation of the phthalocyanines was studied. It was not possible to obtain the Mn(II) complexes by reduction of the corresponding Mn(III) complexes due to the presence of electron donating substituents at the periphery of the phthalocyanines. The (1)H NMRD plots of the PEG500 and choline substituted Mn(III)-phthalocyanine complexes are typical of self-aggregated Mn(III) systems with r1 relaxivities of 4.0 and 5.7mM(-1)s(-1) at 20MHz and 25°C. The Mn(III)-phthalocyanine-PEG4 complex shows no significant cytotoxicity to HeLa cell cultures after 2h of incubation up to 2mM concentration. After 24h of cell exposure to the compound, significant toxicity was observed for all the concentrations tested with IC50 of 1.105mM.

Evaluation of Prostate Cancer Bone Metastases with 18F-NaF and 18F-Fluorocholine PET/CT.

18F-fluorocholine is a specific promising agent for imaging tumor cell proliferation, particularly in prostate cancer, using PET/CT. It is a beneficial tool in the early detection of marrow-based metastases because it excludes distant metastases and evaluates the response to hormone therapy. In addition, 18F-fluorocholine has the potential to differentiate between degenerative and malignant osseous abnormalities because degenerative changes are not choline-avid; however, the agent may accumulate in recent traumatic bony lesions. On the other hand, 18F-NaF PET/CT can indicate increased bone turnover and is generally used in the assessment of primary and secondary osseous malignancies, the evaluation of response to treatment, and the clarification of abnormalities on other imaging modalities or clinical data. 18F-NaF PET/CT is a highly sensitive method in the evaluation of bone metastases from prostate cancer, but it has problematic specificity, mainly because of tracer accumulation in degenerative and inflammatory bone diseases. In summary, 18F-NaF PET/CT is a highly sensitive method, but 18F-fluorocholine PET/CT can detect early bone marrow metastases and provide greater specificity in the detection of bone metastases in patients with prostate cancer. However, the difference seems not to be significant.

Location and orientation relative to the micelle surface for glucagon in mixed micelles with dodecylphosphocholine: EPR and NMR studies.

The spin labels, 5-doxylstearate, 12-doxylstearate, 16-doxylstearate and 1-oxyl-2,2,6,6-tetramethyl-4-dodecylphosphopiperidine, have been incorporated into dodecylphosphocholine micelles and mixed dodecylphosphocholine glucagon micelles. The EPR spectral parameters for the different spin labels and the 1H- and 13C-NMR relaxation rates for nuclei of the detergent molecules indicated that inclusion of up to one spin label molecule per micelle had little influence on the spatial organization of the micelles. Furthermore, the location and environment of the spin labels in the dodecylphosphocholine micelles were not noticeably affected by the addition of glucagon and the 1H-NMR spectra observed for glucagon in mixed spin label/deuterated dodecylphosphocholine/glucagon micelles showed that the different spin labels had essentially no effect on the conformation of glucagon. Approximate spatial locations within the micelle for the nitroxide moieties of the different spin labels were determined from the NMR relaxation rates observed for different nuclei of dodecylphosphocholine. On this basis, the line broadening of individually assigned glucagon 1H-NMR lines by the different spin labels was used to determine the approximate orientation of the polypeptide chain with respect to the micelle surface. Overall, the data indicate that the glucagon backbone runs roughly parallel to the micelle surface, with the depth of immersion adjusted so that polar and apolar side chains can be oriented towards the surface or interior of the micelle, respectively.