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4. Modal characteristics of structures considering dynamic soil-structure interaction effects

Author

Papadopoulos, M, Van Beeumen, R, François, S, Degrande, G, and Lombaert, G

Subjects
Dynamic soil-structure interaction, Perfectly matched layers, Modal characteristics of structures, Non-linear eigenvalue problem, Non-proportional damping, Strategic, Defence & Security Studies, Geophysics, Civil Engineering
Abstract

The modal characteristics of structures are usually computed disregarding any interaction with the soil. This paper presents a finite element-perfectly matched layers model to compute the modal characteristics of 2D and 3D coupled soil-structure systems while taking fully into account dynamic soil-structure interaction. The methodology can facilitate the interpretation of experimentally identified modal characteristics by assessing the importance of dynamic soil-structure interaction.

Published
2018

5. Early management of adult traumatic spinal cord injury in patients with polytrauma: a consensus and clinical recommendations jointly developed by the World Society of Emergency Surgery (WSES) & the European Association of Neurosurgical Societies (EANS)

Author

Picetti, E, Demetriades, A, Catena, F, Aarabi, B, Abu-Zidan, F, Alves, O, Ansaloni, L, Armonda, R, Badenes, R, Bala, M, Balogh, Z, Barbanera, A, Bertuccio, A, Biffl, W, Bouzat, P, Buki, A, Castano-Leon, A, Cerasti, D, Citerio, G, Coccolini, F, Coimbra, R, Coniglio, C, Costa, F, De Iure, F, Depreitere, B, Fainardi, E, Fehlings, M, Gabrovsky, N, Godoy, D, Gruen, P, Gupta, D, Hawryluk, G, Helbok, R, Hossain, I, Hutchinson, P, Iaccarino, C, Inaba, K, Ivanov, M, Kaprovoy, S, Kirkpatrick, A, Klein, S, Kolias, A, Konovalov, N, Lagares, A, Lippa, L, Loza-Gomez, A, Luoto, T, Maas, A, Maciejczak, A, Maier, R, Marklund, N, Martin, M, Melloni, I, Mendoza-Lattes, S, Meyfroidt, G, Munari, M, Napolitano, L, Okonkwo, D, Otomo, Y, Papadopoulos, M, Petr, O, Peul, W, Pudkrong, A, Qasim, Z, Rasulo, F, Reizinho, C, Ringel, F, Rizoli, S, Rostami, E, Rubiano, A, Russo, E, Sarwal, A, Schwab, J, Servadei, F, Sharma, D, Sharif, S, Shiban, E, Shutter, L, Stahel, P, Taccone, F, Terpolilli, N, Thomé, C, Toth, P, Tsitsopoulos, P, Udy, A, Vaccaro, A, Varon, A, Vavilala, M, Younsi, A, Zackova, M, Zoerle, T, Robba, C, Picetti, Edoardo, Demetriades, Andreas K., Catena, Fausto, Aarabi, Bizhan, Abu-Zidan, Fikri M., Alves, Oscar L., Ansaloni, Luca, Armonda, Rocco A., Badenes, Rafael, Bala, Miklosh, Balogh, Zsolt J., Barbanera, Andrea, Bertuccio, Alessandro, Biffl, Walter L., Bouzat, Pierre, Buki, Andras, Castano-Leon, Ana Maria, Cerasti, Davide, Citerio, Giuseppe, Coccolini, Federico, Coimbra, Raul, Coniglio, Carlo, Costa, Francesco, De Iure, Federico, Depreitere, Bart, Fainardi, Enrico, Fehlings, Michael J., Gabrovsky, Nikolay, Godoy, Daniel Agustin, Gruen, Peter, Gupta, Deepak, Hawryluk, Gregory W. J., Helbok, Raimund, Hossain, Iftakher, Hutchinson, Peter J., Iaccarino, Corrado, Inaba, Kenji, Ivanov, Marcel, Kaprovoy, Stanislav, Kirkpatrick, Andrew W., Klein, Sam, Kolias, Angelos, Konovalov, Nikolay A., Lagares, Alfonso, Lippa, Laura, Loza-Gomez, Angelica, Luoto, Teemu M., Maas, Andrew I. R., Maciejczak, Andrzej, Maier, Ronald V., Marklund, Niklas, Martin, Matthew J., Melloni, Ilaria, Mendoza-Lattes, Sergio, Meyfroidt, Geert, Munari, Marina, Napolitano, Lena M., Okonkwo, David O., Otomo, Yasuhiro, Papadopoulos, Marios C., Petr, Ondra, Peul, Wilco C., Pudkrong, Aichholz K., Qasim, Zaffer, Rasulo, Frank, Reizinho, Carla, Ringel, Florian, Rizoli, Sandro, Rostami, Elham, Rubiano, Andres M., Russo, Emanuele, Sarwal, Aarti, Schwab, Jan M., Servadei, Franco, Sharma, Deepak, Sharif, Salman, Shiban, Ehab, Shutter, Lori, Stahel, Philip F., Taccone, Fabio S., Terpolilli, Nicole A., Thomé, Claudius, Toth, Peter, Tsitsopoulos, Parmenion P., Udy, Andrew, Vaccaro, Alexander R., Varon, Albert J., Vavilala, Monica S., Younsi, Alexander, Zackova, Monika, Zoerle, Tommaso, Robba, Chiara, Picetti, E, Demetriades, A, Catena, F, Aarabi, B, Abu-Zidan, F, Alves, O, Ansaloni, L, Armonda, R, Badenes, R, Bala, M, Balogh, Z, Barbanera, A, Bertuccio, A, Biffl, W, Bouzat, P, Buki, A, Castano-Leon, A, Cerasti, D, Citerio, G, Coccolini, F, Coimbra, R, Coniglio, C, Costa, F, De Iure, F, Depreitere, B, Fainardi, E, Fehlings, M, Gabrovsky, N, Godoy, D, Gruen, P, Gupta, D, Hawryluk, G, Helbok, R, Hossain, I, Hutchinson, P, Iaccarino, C, Inaba, K, Ivanov, M, Kaprovoy, S, Kirkpatrick, A, Klein, S, Kolias, A, Konovalov, N, Lagares, A, Lippa, L, Loza-Gomez, A, Luoto, T, Maas, A, Maciejczak, A, Maier, R, Marklund, N, Martin, M, Melloni, I, Mendoza-Lattes, S, Meyfroidt, G, Munari, M, Napolitano, L, Okonkwo, D, Otomo, Y, Papadopoulos, M, Petr, O, Peul, W, Pudkrong, A, Qasim, Z, Rasulo, F, Reizinho, C, Ringel, F, Rizoli, S, Rostami, E, Rubiano, A, Russo, E, Sarwal, A, Schwab, J, Servadei, F, Sharma, D, Sharif, S, Shiban, E, Shutter, L, Stahel, P, Taccone, F, Terpolilli, N, Thomé, C, Toth, P, Tsitsopoulos, P, Udy, A, Vaccaro, A, Varon, A, Vavilala, M, Younsi, A, Zackova, M, Zoerle, T, Robba, C, Picetti, Edoardo, Demetriades, Andreas K., Catena, Fausto, Aarabi, Bizhan, Abu-Zidan, Fikri M., Alves, Oscar L., Ansaloni, Luca, Armonda, Rocco A., Badenes, Rafael, Bala, Miklosh, Balogh, Zsolt J., Barbanera, Andrea, Bertuccio, Alessandro, Biffl, Walter L., Bouzat, Pierre, Buki, Andras, Castano-Leon, Ana Maria, Cerasti, Davide, Citerio, Giuseppe, Coccolini, Federico, Coimbra, Raul, Coniglio, Carlo, Costa, Francesco, De Iure, Federico, Depreitere, Bart, Fainardi, Enrico, Fehlings, Michael J., Gabrovsky, Nikolay, Godoy, Daniel Agustin, Gruen, Peter, Gupta, Deepak, Hawryluk, Gregory W. J., Helbok, Raimund, Hossain, Iftakher, Hutchinson, Peter J., Iaccarino, Corrado, Inaba, Kenji, Ivanov, Marcel, Kaprovoy, Stanislav, Kirkpatrick, Andrew W., Klein, Sam, Kolias, Angelos, Konovalov, Nikolay A., Lagares, Alfonso, Lippa, Laura, Loza-Gomez, Angelica, Luoto, Teemu M., Maas, Andrew I. R., Maciejczak, Andrzej, Maier, Ronald V., Marklund, Niklas, Martin, Matthew J., Melloni, Ilaria, Mendoza-Lattes, Sergio, Meyfroidt, Geert, Munari, Marina, Napolitano, Lena M., Okonkwo, David O., Otomo, Yasuhiro, Papadopoulos, Marios C., Petr, Ondra, Peul, Wilco C., Pudkrong, Aichholz K., Qasim, Zaffer, Rasulo, Frank, Reizinho, Carla, Ringel, Florian, Rizoli, Sandro, Rostami, Elham, Rubiano, Andres M., Russo, Emanuele, Sarwal, Aarti, Schwab, Jan M., Servadei, Franco, Sharma, Deepak, Sharif, Salman, Shiban, Ehab, Shutter, Lori, Stahel, Philip F., Taccone, Fabio S., Terpolilli, Nicole A., Thomé, Claudius, Toth, Peter, Tsitsopoulos, Parmenion P., Udy, Andrew, Vaccaro, Alexander R., Varon, Albert J., Vavilala, Monica S., Younsi, Alexander, Zackova, Monika, Zoerle, Tommaso, and Robba, Chiara

Abstract

Background: The early management of polytrauma patients with traumatic spinal cord injury (tSCI) is a major challenge. Sparse data is available to provide optimal care in this scenario and worldwide variability in clinical practice has been documented in recent studies. Methods: A multidisciplinary consensus panel of physicians selected for their established clinical and scientific expertise in the acute management of tSCI polytrauma patients with different specializations was established. The World Society of Emergency Surgery (WSES) and the European Association of Neurosurgical Societies (EANS) endorsed the consensus, and a modified Delphi approach was adopted. Results: A total of 17 statements were proposed and discussed. A consensus was reached generating 17 recommendations (16 strong and 1 weak). Conclusions: This consensus provides practical recommendations to support a clinician’s decision making in the management of tSCI polytrauma patients.

Published
2024

10. Radiopaque marker colonic transit study in the pediatric population BSPGHAN Motility Working Group consensus statement.

Author

Papadopoulos, M., Mutalib, M., Nikaki, K., Volonaki, E., Rybak, A., Thapar, N., Lindley, K., Borrelli, O., Das, A., Crespi, D., Cleeve, S., and Athanasakos, E.

Subjects
*CHILD patients, *PEDIATRIC gastroenterology, *CONSTIPATION, *HEPATOLOGY, *COLON (Anatomy)
Abstract

Functional constipation (FC) is a common condition in childhood in the United Kingdom and worldwide. Various radiological approaches have been established for diagnostic purposes. The radiopaque marker study (ROMS) is universally accepted and used to assess colonic transit time (CTT) in children with FC. Despite being widely used, there is a lack of standardization with various technical protocols, reproducibility of different populations, the purpose for using investigation, variance in the number of markers used, the amount of study days and calculations, the need to empty the colon before performing the test, and whether to perform on medication or off, or the use of specific diets. As part of the British Society of Paediatric Gastroenterology, Hepatology and Nutrition (BSPGHAN) motility working group (MWG), we decided to explore further into the evidence, in order to provide guidance regarding the use of ROMS in dealing with FC in the pediatric population. [ABSTRACT FROM AUTHOR]

Published
2024
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11. Neonatal Stressors

Author

Delivoria-Papadopoulos, M., Kratimenos, P., Buonocore, Giuseppe, editor, and Bellieni, Carlo Valerio, editor

Published
2017
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17. Prospective, multicentre study of external ventricular drainage-related infections in the UK and Ireland

Author

Jamjoom, Aimun A B, Joannides, Alexis J, Poon, Michael Tin-Chung, Chari, Aswin, Zaben, Malik, Abdulla, Mutwakil A H, Roach, Joy, Glancz, Laurence J, Solth, Anna, Duddy, John, Brennan, Paul M, Bayston, Roger, Bulters, Diederik O, Mallucci, Conor L, Jenkinson, Michael D, Gray, William P, Kandasamy, Jothy, Hutchinson, Peter J, Kolias, Angelos G, Ahmed, Aminul I, Alalade, A, Bailey, M, Basu, S, Baudracco, I, Bhattacharya, A, Bodkin, Pa, Boissaud-cooke, M, Bojanic, S, Buxton, N, Corns, R, Coulter, C, Coulter, I, Critchley, G, Dando, A, Dardis, R, Dyson, E, Edwards, R, Garnett, M, Gatcher, S, Georges, H, Hallet, J, Harte, J, Haylock-vize, P, Humphreys, H, Kitchen, J, Lawson Mclean, A, Loan, JJM, Ma, R, Madder, H, Manning, A, Mcelligott, S, Mukerji, N, Narayanamurthy, H, O’brien, D, Okasha, M, Papadopoulos, M, Phan, V, Phang, I, Poots, J, Rajaraman, C, Ross, N, Sharouf, F, Shastin, D, Simms, N, Steele, L, Tajsic, T, Talibi, S, Thanabalasundaram, G, Vintu, M, Wan, Y, Wang, D, Watkins, L, Whitehouse, K, Whitfield, PC, and Williams, A

Published
2018
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18. Neonatal Stressors

Author

Delivoria-Papadopoulos, M., Mishra, O. P., Buonocore, Giuseppe, editor, and Bellieni, Carlo V., editor

Published
2008
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21. Synthesis and preclinical evaluation of rhenium and technetium-99m “4 + 1” mixed-ligand complexes bearing quinazoline derivatives as potential EGFR imaging agents

Author

Kiritsis, C., Shegani, A., Makrypidi, K., Roupa, I., Lazopoulos, A., Panagiotopoulou, A., Triantopoulou, S., Paravatou-Petsotas, M., (0000-0001-5286-4319) Pietzsch, H.-J., Pelecanou, M., Papadopoulos, M., Pirmettis, I., Kiritsis, C., Shegani, A., Makrypidi, K., Roupa, I., Lazopoulos, A., Panagiotopoulou, A., Triantopoulou, S., Paravatou-Petsotas, M., (0000-0001-5286-4319) Pietzsch, H.-J., Pelecanou, M., Papadopoulos, M., and Pirmettis, I.

Abstract

Epidermal growth factor receptors (EGFR) of tyrosine kinase (TK) have shown high expression levels in most cancers and are considered a promising target for cancer diagnosis and therapy. Expanding the investigation for novel targeted radiopharmaceuticals, an EGFR inhibitor such as 4-aminoquinazoline derivatives along with a radionuclide such as technetium-99m (99mTc) could be ideal. Thus, we report herein the synthesis, characterization, and biological evaluation of new “4 + 1” mixed-ligand ReIII- and 99mTcIII-complexes of the general formula [99mTc][Tc(NS3)(CN-R)] bearing tris(2-mercaptoethyl)-amine (NS3) as the tetradentate tripodal ligand and a series of isocyanide derivatives (CN-R) of tyrosine kinase inhibitor (3-bromophenyl)quinazoline-4,6-diamine as the monodentate ligand. The quinazoline isocyanide derivatives 4a-d were prepared in two steps and reacted with the [Re(NS3)PMe2Ph] precursor leading to the final complexes 5a-d in high yield. All compounds were characterized by elemental analysis, IR, and NMR spectroscopies. In vitro studies, for their potency to inhibit the cell growth, using intact A431 cells indicate that the quinazoline derivatives 4a-d and the Re complexes 5a-d significantly inhibit the A431 cell growth. In addition, the EGFR autophosphorylation study of complex 5b shows an IC50 value in the nanomolar range. The corresponding “4 + 1” 99mTc-complexes 6a-d were prepared by employing the [99mTc]TcEDTA intermediate and the appropriate monodentate 4a-d in a two-step synthetic procedure with a radiochemical yield (RCY) from 63 to 77 % and a radiochemical purity (RCP) > 99 % after HPLC purification. Their structures have been established by HPLC comparative studies using the well-characterized Re-complexes 5a-d as reference. All 99mTc-complexes remain stable for at least 6 h, and their logD7.4 values confirmed their anticipated lipophilic character. Biodistribution studies in healthy Swiss albino mice of 99mTc-complexes showed hepatobiliary excreti

Published
2022

23. Sustainable Ecotourism through Cutting-Edge Technologies

Author

Pavlidis, G. Solomou, A. Stamouli, S. Papavassiliou, V. Kritsis, K. Kiourt, C. Sevetlidis, V. Karetsos, G. Trigas, P. Kougioumoutzis, K. Goula, K. Proutsos, N. Pistikos, G. Theodoridis, Y. Galanopoulos, E. Paraskevas, N. Foskolou, U. Papadopoulos, M.

Abstract

Tourism is a phenomenon that dates back to ancient times. Ancient Greek philosophers recognised, adopted, and promoted the concept of rest-based tourism. Ecotourism is a particular type of tourism that connects with activities that take place in nature, without harming it, along with the herbal and animal wealth. According to estimates, the global ecotourism industry is currently booming due to various reasons, and it is becoming an important factor of sustainable regional development. This article presents the vision, work, and outcomes of project AdVENt, a project focusing natively in sustainable ecotourism through natural science and technological innovation. AdVENt’s study area includes the National Parks of Oiti (or Oeta) and Parnassus in Central Greece, where there is a remarkable native flora with a high endemism rate integrated with areas of cultural value and national and European hiking routes and paths of varying difficulty. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.

Published
2022

27. Study of Optimal Perimetric Testing In Children (OPTIC): developing consensus and setting research priorities for perimetry in the management of children with glaucoma

Author

Patel, D. E., Cumberland, P. M., Walters, B. C., Abbott, J., Brookes, J., Edmunds, B., Khaw, P. T., Lloyd, I. C., Papadopoulos, M., Sung, V., Cortina-Borja, M., Rahi, J. S., Walters, B., Cumberland, P., Russell-Eggitt, I., Timms, C., Moore, A., Garway-Heath, D., Viswanathan, A., Liasis, A., Crabb, D. P., Patel, D., and Rahi, J.

Subjects
RJ, RE
Abstract

Background: Perimetry is important in the management of children with glaucoma, but there is limited evidence-based guidance on its use. We report an expert consensus-based study to update guidance and identify areas requiring further research. \ud \ud Methods: Experts were invited to participate in a modified Delphi consensus process. Panel selection was based on clinical experience of managing children with glaucoma and UK-based training to minimise diversity of view due to healthcare setting. Questionnaires were delivered electronically, and analysed to establish ‘agreement’. Divergence of opinions was investigated and resolved where possible through further iterations. \ud \ud Results: 7/9 experts invited agreed to participate. Consensus (≥5/7 (71%) in agreement) was achieved for 21/26 (80.8%) items in 2 rounds, generating recommendations to start perimetry from approximately 7 years of age (IQR: 6.75–7.25), and use qualitative methods in conjunction with automated reliability indices to assess test quality. There was a lack of agreement about defining progressive visual field (VF) loss and methods for implementing perimetry longitudinally. Panel members highlighted the importance of informing decisions based upon individual circumstances—from gauging maturity/capability when selecting tests and interpreting outcomes, to accounting for specific clinical features (e.g. poor IOP control and/or suspected progressive VF loss) when making decisions about frequency of testing. \ud \ud Conclusions: There is commonality of expert views in relation to implementing perimetry and interpreting test quality in the management of children with glaucoma. However, there remains a lack of agreement about defining progressive VF loss, and utilising perimetry over an individuals’ lifetime, highlighting the need for further research.

Published
2021

35. Synthesis and in vitro evaluation of gold nanoparticles functionalized with thiol ligands for robust radiolabeling with99mTc

Author

Apostolopoulou, A. Chiotellis, A. Salvanou, E.-A. Makrypidi, K. Tsoukalas, C. Kapiris, F. Paravatou-Petsotas, M. Papadopoulos, M. Pirmettis, I.C. Koźmiński, P. Bouziotis, P.

Abstract

Radiolabeled gold nanoparticles (AuNPs) have been widely used for cancer diagnosis and therapy over recent decades. In this study, we focused on the development and in vitro evaluation of four new Au nanoconjugates radiolabeled with technetium-99m (99m Tc) via thiol-bearing ligands attached to the NP surface. More specifically, AuNPs of two different sizes (2 nm and 20 nm, referred to as Au(2) and Au(20), respectively) were functionalized with two bifunctional thiol ligands (referred to as L1H and L2H). The shape, size, and morphology of both bare and ligand-bearing AuNPs were characterized by transmission electron microscopy (TEM) and dynamic light scattering (DLS) techniques. In vitro cytotoxicity was assessed in 4T1 murine mammary cancer cells. The AuNPs were successfully radiolabeled with99mTc-carbonyls at high radiochemical purity (>95%) and showed excellent in vitro stability in competition studies with cysteine and histidine. Moreover, lipophilicity studies were performed in order to determine the lipophilicity of the radiolabeled con-jugates, while a hemolysis assay was performed to investigate the biocompatibility of the bare and functionalized AuNPs. We have shown that the functionalized AuNPs developed in this study lead to stable radiolabeled nanoconstructs with the potential to be applied in multimodality imaging or for in vivo tracking of drug-carrying AuNPs. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Published
2021

36. Copyright Through the Prism of the Law and Economics Movement: A Scientific Approach

Author

Koutras, Nikos, Papadopoulos, M., Koutras, Nikos, and Papadopoulos, M.

Abstract

This paper discusses aspects of economic analysis of law developed because of the status quo existing on the Internet and of the evolution of legal theory on copyright. It also explores the massive increase of interest in the law and economics of intellectual property during the first decade of twenty-first century. The paper argues that law and economics discourse on copyright foregrounds policymaking with a focus on copyright’s economic ramifications. This paper also examines Coase’s theorem and its influence on considerations about copyright regulatory frameworks and potential reform to keep abreast of ongoing technological advancements and their impact on copyright protection in the digital age.

Published
2021

37. Openness Through the Lenses of the Three-Step-Test: International Perspectives on Copyright Protection

Author

Papadopoulos, M., Koutras, Nikos, Papadopoulos, M., and Koutras, Nikos

Abstract

This paper is focused on openness movement and the principles that said movement declared regarding the use of works set under copyright protection to enable for open access works. The three-step-test legal edifice is deeply rooted in international copyright law; its meaning and application is of vital importance for any consideration of amending copyright law with the aim to include provisions for openness. Unless a provision for openness passes the three-step-test there can be no sustainable amendment of copyright law in favour of openness.

Published
2021

40. Biological evaluation of complexes of cyclopentadienyl M(CO)3+ (M = Re, 99mTc) with high blood–brain barrier penetration potential as brain cancer agents.

Author

Mavroidi, B., Kaminari, A., Makrypidi, K., Shegani, A., Bouziotis, P., Pirmettis, I., Papadopoulos, M., Sagnou, M., and Pelecanou, M.

Subjects
BLOOD-brain barrier, GLIOMAS, APOPTOSIS, BRAIN tumors, REACTIVE oxygen species, MOLECULAR structure
Abstract

Summary: To address the major medical need for effective chemotherapeutics/diagnostics for brain cancer, in this work three cyclopentadienyl M(CO)3+ (M = Re, 99mTc) complexes, which cross the blood-brain barrier (BBB) in high % and are designed to mimic the anticancer agent 2-phenylbenzothiazole, are in vitro and in vivo evaluated for anticancer action. The study includes cytotoxicity and uptake studies in cancer and healthy neuronal cell lines, mechanistic investigation of potential anticancer pathways, and biodistribution studies in mice bearing glioblastoma xenografts. The stable Re complexes exhibit selective uptake and significant antiproliferative effect, particularly against U-251 MG glioblastoma cells, with no significant toxicity in healthy neurons, demonstrating the suitability of this type of complexes to serve as selective therapeutic/imaging agents for brain cancer. Furthermore, they result in the generation of elevated Reactive Oxygen Species (ROS) levels, and lead to significant G2/M arrest followed by apoptosis. Biodistribution studies in U-251 MG xenograft bearing mice with the radioactive 99mTc complex that exhibits the highest BBB penetration, show retention at the tumor-site offering a diagnostic prospect and, in addition, indicating the capability of the Re analogue to accumulate at the tumor site for therapeutic action. Overall, the complexes demonstrate significant anticancer properties that, combined with their high BBB penetration potential, render them strong candidates for further evaluation as brain cancer agents. [ABSTRACT FROM AUTHOR]

Published
2022
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41. Synthesis, characterization and evaluation of 68Ga labelled monomeric and dimeric quinazoline derivatives of the HBED-CC chelator targeting the epidermal growth factor receptor

Author

Liolios, C. Shegani, A. Roupa, I. Kiritsis, C. Makarem, A. Paravatou-Petsotas, M. Pelecanou, M. Bouziotis, P. Papadopoulos, M. Kopka, K. Pirmettis, I.

Abstract

Tyrosine kinase (TK) receptors including epidermal growth factor receptors (EGFRs) are known to be overexpressed in a wide variety of solid tumors associated with poor prognosis. The HBED-CC chelator N,N′-bis[2-hydroxy-5-(carboxyethyl)benzyl]ethylenediamine-N,N′-diacetic acid 1 was coupled via one or both its propionic acid moieties with the quinazoline EGFR-TK inhibiting pharmacophore 4-amino-N-(4-((3-bromophenyl)amino)quinazolin-6-yl)butanamide 3 resulting in either a monomeric 4 or a dimeric 5 species. Ligands 4 and 5 reacted with Ga3+ generating the corresponding complexes Ga4 and Ga5. Both ligands and complexes were characterized with mass spectrometry and NMR spectroscopy and evaluated in vitro with MTT assays in A431 cells, where they showed IC50 values in the range 51.6 to 68.8 μM. Labeling of ligands 4 and 5 with the PET radionuclide 68Ga was quantitative and resulted in tracers [68Ga]Ga4 and [68Ga]Ga5 with radiochemical purities greater than 98%, which were also characterised by comparative RP-HPLC studies with Ga4 and Ga5 respectively. Radiotracers [68Ga]Ga4 and [68Ga]Ga5 were stable (intact tracer over 98%) in the reaction mixture (120 min) and in human serum (30 min). Both tracers were evaluated in vivo with biodistribution experiments in SCID mice bearing A431 tumors presenting tumor uptake of 1.34 for [68Ga]Ga4 and 1.01 %ID/g for [68Ga]Ga5 at 5 min, which was slightly decreased at 60 min p.i. and then remained stable until 120 min p.i. To the best of our knowledge, this is the first report of monomeric and dimeric quinazoline conjugates with the chelator HBED-CC, which can serve as a basis for further development of EGFR-TKI targeting tracers. © 2020 Elsevier Inc.

Published
2020

43. (S)-(2-(2'-pyridyl)ethyl)cysteamine and (S)-(2-(2'-pyridyl)ethyl)-D,L-homocystenine as ligands for the 'fac-[M(CO)3](super +)' (M=Re, (super 99m) Tc) core

Author

Karagiorgou O., Patsis, G., Pelecanou, M., Raptopoulou, C. P., Terzis, A., Siatra-Papastaikoudi, T., Alberto, R., Pirmettis, I., and Papadopoulos, M.

Subjects
Cysteamine -- Chemical properties, Homocysteine -- Chemical properties, Ligands (Biochemistry) -- Research, Chemistry
Abstract

The products obtained by the reaction of fac-[NEt4]2[Re(CO)3Br3] and fac-[(super 99m)Tc(CO)3(H2O)3](super +) with the (S)-(2-(2'-pyridyl)ethyl)cysteamine, L1, and (S)-(2-(2'-pyridyl)ethyl)-D,L-homocysteine, L2, ligands are described. It is concluded that (S)-(2-(2'-pyridyl)ethyl)cysteamine and homocysteine could be easily N- or S-derivatized by a bioactive molecule of interest, both the NSN or NSO ligand systems could be used to develop target-specific radiopharmaceuticals or diagnosis and therapy.

Published
2005

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