Background / Aim. MDSCs suppress immune responses via a series of inhibitory mechanisms, which ultimately could lead to tumor growth. B7-H4 expression is significantly associated with poor outcome and promotion of tumor cell proliferation, invasion and migration in patients with various cancers. Data concerning B7-H4 expression in lung cancers, either on tumor or immunological cells, are still sporadically. To estimate and correlate the number of CD14+B7-H4+MDSC in blood and lung tumor microcirculation with clinical stage, histology type of tumor, TNM stadium, nodal status and disease outspread. Methods. 44 lung cancer patients (III and IV clinical stage) and 30 healthy controls. CD14+B7-H4+ MDSC number was estimated by flowcytometry in blood and tumor microcirculation samples of each patient. Results. CD14+B7-H4+MDSC number was significantly higher in patient’s samples comparing to controls. CD14+B7-H4+MDSC was significantly increased in tumor comparing to blood sample of same patient. Clinical stage III patients had increased number of the CD14+B7-H4+ MDSC comparing to stage IV, in both type of samples. According to histology SCLC patients had the highest average CD14+B7-H4+MDSC number, significantly increased comparing to patients with squamous and large cell LC histology in tumor. Tumor size was directly associated with the number of the CD14+B7-H4+MDSC, both in blood and tumor samples. Furthermore, nodal involvement was associated with gradual increase of the CD14+B7-H4+MDSC number, being the highest in the N3 group, again both in blood and tumor samples. Finally, we have detected higher CD14+ B7-H4+MDSC number in the samples of patients without metastases. Conclusion. CD14+B7-H4+MDSC number in LC patients is significantly associated with tumor histology type, lymph node involvement, disease extent degree and tumor size. Concerning their large number in LC tumor microenvironment together with immunosuppressive capacities, CD14+B7-H4+MDSC could represent important tumor promoting factor in LC pathophysiology.

It was reported that novel O,O′-diethyl-(S, S)-ethylenediamine-N,N′-di-2-(3-cyclohexyl) propanoate dihydrochloride (DE-EDCP) displayed in vitro antiproliferative activity on several human and mouse cancer cell lines, which was comparable to that of the prototypical anticancer drug cisplatin. In order to reveal its toxicity profile, acute and repeated-dose toxicity studies were performed in Naval Medical Research Institute (NMRI) Han mice. The intravenous LD50 values of DE-EDCP were found to be 95.3 and 101.3 mg/kg body weight in female and male mice, respectively. In the subacute toxicity study, DE-EDCP was administered intravenously at the doses of 15, 25, and 40 mg/kg/day for a period of 28 days. There were no adverse effects on general condition, growth, feed and water consumption, and hematological parameters. There was a significant increase in urea and alanine aminotransferase in female mice and aspartate aminotransferase and alkaline phosphatase in both genders in 40 mg/kg/day dose-treated group. The histopathological changes confined to the liver and kidney, but in other organs were not found. Satellite group revealed that changes in the kidney and liver were less pronounced, suggesting their reversibility. Interactions with DNA could also be of importance for understanding DE-EDCP toxic side effects. Hyperchromic effect obtained with ultraviolet–visible, suggested electrostatic interactions between DE-EDCP and calf thymus DNA. The toxicity testing of DE-EDCP was conducted to predict human outcomes.

A series of new (S,S)-ethylenediamine-N,N′-di-2-(3-cyclohexyl)propanoate esters has shown cytotoxic activity towards human leukemic cell lines. The aim of this study was to develop and validate a bioanalytical method for quantification of (S,S)-O,O-diethyl-ethylenediamine-N,N′-di-2-(3-cyclohexyl)propanoate dihydrochlorides (DE-EDCP) and its metabolite, substituted propanoic acid (EDCP), in mouse serum by ultra high-performance liquid chromatography—tandem mass spectrometry (UHPLC—MS/MS). Structural analog, derivative of 1,3-propanediamine, was used as an internal standard (IS). Sample preparation employed protein precipitation by acetonitrile and subsequent centrifugation. Optimal UHPLC separation conditions were set to achieve simultaneous determination of both compounds in a short run time of 6 min. Additionally, the selected reaction monitoring (SRM) mode developed in this method allowed a highly sensitive, accurate, and precise identification of compounds of interest. The lower limit of quantitation (...

BACKGROUND Benzodiazepines have a direct bronchodilatory effect. Methacholine is a non-selective muscarinic receptor agonist causing bronchoconstriction. AIM To examine the effects of inhaled benzodiazepines, modulating bronchoconstriction induced by methacholine in patients with asthma. PATIENTS AND METHODS Twelve patients with well controlled asthma were studied. On the first day, after determining the initial values of pulmonary function, a dose response curve was carried out with progressive doses of methacholine. After the last dose, when at least a 20% drop of the initial forced expiratory volume in the first second (FEV1) was achieved, vital capacity (VC) and FEV1 were measured at 7, 15 and 30 minutes after provocation. On the second day a diazepam aerosol was inhaled by the patients prior to the same protocol with methacholine. RESULTS In the first day of testing, methacholine inhalation (6 mg/mL) led to a significant drop in FEV1 from 2.98 to 1.69 L. On the second day of study, in the same patients, previous inhalation with diazepam reduced the changes of FEV1 after inhalation of methacholine. This parameter decreased from 2.48 to 2.21 L. CONCLUSIONS Inhalation of benzodiazepines reduce bronchoconstriction after a methacholine challenge in patients with asthma.

Table of contents OP03 Selective extraction of medically-related radionuclides from proton-irradiated thorium targets V. Radchenko, J.W. Engle, C. Roy, J. Griswold, M.F. Nortier, E.R. Birnbaum, M. Brugh, S. Mirzadeh, K. D. John, M.E. Fassbender OP04 Comparison of [68Ga]FSC(succ-RGD)3 and [68Ga]NODAGA-RGD for PET imaging of αvβ3 integrin expression Chuangyan Zhai, Gerben M. Franssen, Milos Petrik, Peter Laverman, Clemens Decristoforo OP05 A new NPY-Y1R targeting peptide for breast cancer PET imaging Ait-Mohand Samia, Dumulon-Perreault Véronique, Guérin Brigitte OP06 The influence of multivalency on CCK 2 receptor targeting D. Summer, A. Kroess, C. Rangger, H. Haas, P. Laverman, F. Gerben, E. von Guggenberg, C.Decristoforo OP07 SPECT Imaging of αvβ3 Expression by [99mTc(N)PNP43]- Bifunctional Chimeric RGD Peptide not Cross-Reacting with αvβ5 Cristina Bolzati, Nicola Salvarese, Fiorenzo Refosco, Laura Meléndez-Alafort, Debora Carpanese, Antonio Rosato, Michele Saviano, Annarita Del Gatto, Daniela Comegna, Laura Zaccaro OP09 New dienophiles for the inverse-electron-demand Diels-Alder reaction and for pretargeted PET imaging Emilie Billaud, Muneer Ahamed, Frederik Cleeren, Elnaz Shahbazali, Tim Noël, Volker Hessel, Alfons Verbruggen and Guy Bormans OP10 New complexing agent for Al18F-labelling of heat-sensitive biomolecules: Synthesis and preclinical evaluation of Al18F-RESCA1-HAS Cleeren F, Lecina J, Koole M, Verbruggen A and Bormans G OP11 A novel versatile precursor efficient for F-18 radiolabelling via click-chemistry B. Lugatoa, S. Stucchia, E.A. Turollaa, L. Giulianoa, S.Toddea, P. Ferraboschib OP12 A general applicable method to quantify unidentified UV impurities in radiopharmaceuticals R.P. Klok, M.P.J. Mooijer, N.H. Hendrikse, A.D. Windhorst OP13 Development of [18F]Fluoro-C-glycosides to radiolabel peptides Collet C., Petry N., Chrétien F., Karcher G., Pellegrini-Moïse N., Lamandé-Langle S. OP14 A Microfluidic Approach for the 68Ga-labeling of PSMAHBED-CC and NODAGA-RGD Sarah Pfaff, Cecile Philippe, Markus Mitterhauser, Marcus Hacker, Wolfgang Wadsak OP16 Surprising reactivity of astatine in the nucleophilic substitution of aryliodonium salts: application to the radiolabeling of antibodies François Guérard, Yong-Sok Lee, Sébastien Gouard, Kwamena Baidoo, Cyrille Alliot, Michel Chérel, Martin W. Brechbiel, Jean-François Gestin OP17 64Cu-NOTA-pertuzumab F(ab')2 fragments, a second-generation probe for PET imaging of the response of HER2-positive breast cancer to trastuzumab (Herceptin) Lam K, Chan C, Reilly RM OP18 Development of radiohalogenated analogues of a avb6-specific peptide for high LET particle emitter targeted radionuclide therapy of cancer Salomé Paillas, John Marshall, Jean-Pierre Pouget, Jane Sosabowski OP19 Ligand Specific Efficiency (LSE) as a guide in tracer optimization Emmanuelle Briard, Yves P. Auberson, John Reilly, Mark Healy, David Sykes OP23 The radiosynthesis of an 18F-labeled triglyceride, developed to visualize and quantify brown adipose tissue activity Andreas Paulus, Wouter van Marken Lichtenbelt,Felix Mottaghy, Matthias Bauwens OP24 Influence of the fluorescent dye on the tumor targeting properties of dual-labeled HBED-CC based PSMA inhibitors Baranski, Ann-Christin, Schäfer, Martin, Bauder-Wüst, Ulrike, Haberkorn, Uwe, Eder, Matthias, Kopka, Klaus OP25 [18F]MEL050 as a melanin PET tracer : fully automated radiosynthesis and evaluation for the detection of pigmented melanoma in mice pulmonary metastases Chaussard M, Hosten B, Vignal N, Tsoupko-Sitnikov V, Hernio N, Hontonnou F, Merlet P, Poyet JL, Sarda-Mantel L, Rizzo-Padoin N OP26 Design and Preclinical Evaluation of Novel Radiofluorinated PSMA Targeting Ligands Based on PSMA-617 J. Cardinale, M. Schäfer, M. Benešová, U. Bauder-Wüst, O. Seibert, F. Giesel, U. Haberkorn, M. Eder, K. Kopka OP27 A novel radiolabeled peptide for PET imaging of prostate cancer: 64Cu-DOTHA2-PEG-RM26 Mansour Nematallah, Paquette Michel, Ait-Mohand Samia, Dumulon-Perreault Véronique, Lecomte Roger, Guérin Brigitte OP29 Biodistribution of [18F]Amylovis®, a new radiotracer PET imaging of β-amyloid plaques Fernandez-Maza L, Rivera-Marrero S, Prats Capote A, Parrado-Gallego A, Fernandez-Gomez I, Balcerzyk M, Sablon-Carrazana M, Perera-Pintado A, Merceron-Martinez D, Acosta-Medina E, Rodriguez-Tanty C OP30 Synthesis and preclinical evaluation of [11C]-BA1 PET tracer for the imaging of CSF-1R Bala Attili, Muneer Ahamed, Guy Bormans OP31 In vivo imaging of the MCHR1 in the ventricular system via [18F]FE@SNAP C. Philippe, M. Zeilinger, T. Scherer, C. Fürnsinn, M. Dumanic, W. Wadsak, M. Hacker, M. Mitterhauser OP32 Synthesis of the first carbon-11 labelled P2Y12 receptor antagonist for imaging the anti-inflammatory phenotype of activated microglia B. Janssen, D.J. Vugts, G.T. Molenaar, U. Funke, P.S. Kruijer, F. Dollé, G. Bormans, A.A. Lammertsma, A.D. Windhorst OP33 Radiosynthesis of a selective HDAC6 inhibitor [11C]KB631 and in vitro and ex vivo evaluation Koen Vermeulen, Muneer Ahamed, Michael Schnekenburger, Mathy Froeyen, Dag Erlend Olberg, Marc Diederich, Guy Bormansa OP34 Improving metabolic stability of fluorine-18 labelled verapamil analogues Raaphorst RM, Luurtsema G, Lammertsma AA, Elsinga PH, Windhorst AD OP36 Development of a novel PET tracer for the activin receptor-like kinase 5 Lonneke Rotteveel, Uta Funke, Peter ten Dijke, Harm Jan Bogaard, Adriaan A. Lammertsma, Albert D. Windhorst OP37 SPECT imaging and biodistribution studies of 111In-EGF-Au-PEG nanoparticles in vivo Lei Song, Sarah Able, Nadia Falzone, Veerle Kersemans, Katherine Vallis OP38 Melanoma targeting with [99mTc(N)(PNP3)]-labeled NAPamide derivatives: preliminary pharmacological studies Davide Carta, Nicola Salvarese, Wiebke Sihver, Feng Gao, Hans Jürgen Pietzsch, Barbara Biondi, Paolo Ruzza, Fiorenzo Refosco, Cristina Bolzati OP39 [68Ga]NODAGA-RGD: cGMP synthesis and data from a phase I clinical study Roland Haubner, Armin Finkensted, Armin Stegmair, Christine Rangger, Clemens Decristoforo, Heinz Zoller, Irene J. Virgolin OP44 Implementation of a GMP-grade radiopharmacy facility in Maastricht Ivo Pooters, Maartje Lotz, Roel Wierts, Felix Mottaghy, Matthias Bauwens OP45 Setting up a GMP production of a new radiopharmaceutical Forsback, Sarita, Bergman Jörgen, Kivelä Riikka OP48 In vitro and in vivo evaluation of 68-gallium labeled Fe3O4-DPD nanoparticles as potential PET/MRI imaging agents M. Karageorgou, M. Radović, C. Tsoukalas, B. Antic, M. Gazouli, M. Paravatou-Petsotas, S. Xanthopouls, M. Calamiotou, D. Stamopoulos, S. Vranješ-Durić, P. Bouziotis OP49 Fast PET imaging of inflammation using 68Ga-citrate with Fe-containing salts of hydroxy acids A. S. Lunev, A. A. Larenkov, K.A. Petrosova, O. E. Klementyeva, G. E. Kodina PP01 Installation and validation of 11C-methionine synthesis Kvernenes, O.H., Adamsen, T.C.H. PP02 Fully automated synthesis of 68Ga-labelled peptides using the IBA Synthera® and Synthera® Extension modules René Martin, Sebastian Weidlich, Anna-Maria Zerges, Cristiana Gameiro, Neva Lazarova, Marco Müllera PP03 GMP compliant production of 15O-labeled water using IBA 18 MeV proton cyclotron Gert Luurtsema, Michèl de Vries, Michel Ghyoot, Gina van der Woude, Rolf Zijlma, Rudi Dierckx, Hendrikus H. Boersma, Philip H. Elsinga PP04 In vitro Nuclear Imaging Potential of New Subphthalocyanine and Zinc Phthalocyanine Fatma Yurt Lambrecht, Ozge Er, Mine Ince, Cıgır Biray Avci, Cumhur Gunduz, Fatma Aslihan Sarı PP05 Synthesis, Photodynamic Therapy Efficacy and Nuclear Imaging Potential of Zinc Phthalocyanines Kasim Ocakoglu, Ozge Er, Onur Alp Ersoz, Fatma Yurt Lambrecht, Mine Ince, Cagla Kayabasi, Cumhur Gunduz PP06 Radio-U(H)PLC – the Search on the Optimal Flow Cell for the γ-Detector Torsten Kniess, Sebastian Meister, Steffen Fischer, Jörg Steinbach PP07 Radiolabeling, characterization & biodistribution study of cysteine and its derivatives with Tc99m Rabia Ashfaq, Saeed Iqbal, Atiq-ur-Rehman, Irfan ullah Khan PP08 Radiolabelling of poly (lactic-co.glycolic acid) (PLGA) nanoparticles with 99mTC R Iglesias-Jerez, Cayero-Otero, L. Martín-Banderas, A. Perera-Pintado, I. Borrego-Dorado PP09 Development of [18F]PD-410 as a non-peptidic PET radiotracer for gastrin releasing peptide receptors Ines Farinha-Antunes, Chantal Kwizera, Enza Lacivita, Ermelinda Lucente, Mauro Niso, Paola De Giorgio, Roberto Perrone, Nicola A. Colabufo, Philip H. Elsinga, Marcello Leopoldo PP10 An improved nucleophilic synthesis of 2-(3,4-dimethoxyphenyl)-6-(2-[18F]fluoroethoxy) benzothiazole ([18F]FEDMBT), potential diagnostic agent for breast cancer imaging by PET V.V. Vaulina, O.S. Fedorova, V.V. Orlovskaja, С.L. Chen, G.Y. Li, F.C. Meng, R.S. Liu, H.E. Wang, R.N. Krasikova PP11 Internal radiation dose assessment of radiopharmaceuticals prepared with accelerator-produced 99mTc Laura Meléndez-Alafort, Mohamed Abozeid, Guillermina Ferro-Flores, Anna Negri, Michele Bello, Nikolay Uzunov, Martha Paiusco, Juan Esposito, Antonio Rosato PP12 A specialized five-compartmental model software for pharmacokinetic parameters calculation Laura Meléndez-Alafort, Cristina Bolzati, Guillermina Ferro-Flores, Nicola Salvarese, Debora Carpanese, Mohamed Abozeid, Antonio Rosato, Nikolay Uzunov PP13 Molecular imaging of the pharmacokinetic behavior of low molecular weight 18F-labeled PEtOx in comparison to 89Zr-labeled PEtOx Palmieri L, Verbrugghen T, Glassner M, Hoogenboom R, Staelens S, Wyffels L PP14 Towards nucleophilic synthesis of the α-[18F]fluoropropyl-L-dihydroxyphenylalanine V. V. Orlovskaja, O. F. Kuznetsova, O. S. Fedorova, V. I. Maleev, Yu. N. Belokon, A. Geolchanyan, A. S. Saghyan, L. Mu, R. Schibli, S. M. Ametamey, R. N. Krasikova PP15 A convenient one-pot synthesis of [18F]clofarabine Revunov, Evgeny, Malmquist, Jonas, Johnström, Peter, Van Valkenburgh, Juno, Steele, Dalton, Halldin, Christer, Schou, Magnus PP16 BODIPY-estradiol conjugates as multi-modality tumor imaging agents Samira Osati,Michel P

BACKGROUND/AIM The cell line C6 is a continuous cell line of rat glioma and, as a transplantable line, is frequently used for induction into in vivo model of primary brain tumor. It is believed that, pursuant to its histological traits and biological behavior, this experimental tumor corresponds to human anaplastic astrocytoma of grade II/III, which is characterized by proliferative and invasive potency, and marked cell differentiation. The aim of this study was to determine macroscopic analysis of rat brain with implanted tumor during tumorigenesis, histological features of tumor cells of induced brain tumor and markers of proliferation (proliferation cell nuclear antigen - PCNA, cytokeratin - CK 19) and differentiation (glial fibrillary acidic protein -GFAP) in rat brain with implanted tumor. METHODS To determine histological structure of the brain with implanted C6 cells, we used brain sections stained for hematoxylin-eosin or kresyl violet, whereas other sections were immunohistochemically stained for GFAP, CK 19 and PCNA. RESULTS A statistically significant difference in weights of the left and right brain hemispheres with implanted tumors during tumorigenesis in as soon as 7 days from the day of inducing tumors was revealed. The tumor was of cellular type, with distinct pleomorphism of cells and frequent hyperchromasia of the nucleus. Immunohistochemical staining for PCNA revealed a significant number of positive cells on the days 7, 14 and 21 day following the implantation of C6 cells. CK 19 positive cells were present in both brain hemispheres, and numerous GFAP positive astrocytes were found around the puncture lesion. CONCLUSIONS Within the experimental conditions of the present research, C6 glioma did not demonstrate any relevant deviations concerning development, clinical symptomatology and macroscopic anatomy relative to those already described in the literature.