Search

Your search keyword '"Johnström P"' showing total 153 results
Start Over Author "Johnström P"
153 results on '"Johnström P"'

1. Brain exposure of osimertinib in patients with epidermal growth factor receptor mutation non‐small cell lung cancer and brain metastases: A positron emission tomography and magnetic resonance imaging study

Author

Simon Ekman, Zsolt Cselényi, Andrea Varrone, Aurelija Jucaite, Heather Martin, Magnus Schou, Peter Johnström, Gianluca Laus, Rolf Lewensohn, Andrew P. Brown, Jasper van derAart, Karthick Vishwanathan, and Lars Farde

Subjects
Therapeutics. Pharmacology, RM1-950, Public aspects of medicine, RA1-1270
Abstract

Abstract Brain metastases (BMs) are associated with poor prognosis in epidermal growth factor receptor mutation‐positive (EGFRm) non‐small cell lung cancer (NSCLC). Osimertinib is a third‐generation, irreversible, EGFR‐tyrosine kinase inhibitor that potently and selectively inhibits EGFR‐sensitizing and T790M resistance mutations with efficacy in EGFRm NSCLC including central nervous system (CNS) metastases. The open‐label phase I positron emission tomography (PET) and magnetic resonance imaging (MRI) study (ODIN‐BM) assessed [11C]osimertinib brain exposure and distribution in patients with EGFRm NSCLC and BMs. Three dynamic 90‐min [11C]osimertinib PET examinations were acquired together with metabolite‐corrected arterial plasma input functions at: baseline, after first oral osimertinib 80 mg dose, and after greater than or equal to 21 days of osimertinib 80 mg q.d. treatment. Contrast‐enhanced MRI was performed at screening and after 25–35 days of osimertinib 80 mg q.d.; treatment effect was assessed per CNS Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and per volumetric changes in total BM using a novel analysis approach. Four patients (aged 51–77 years) completed the study. At baseline, ~1.5% injected radioactivity reached the brain (IDmax[brain]) 22 min (median, Tmax[brain]) after injection. Total volume of distribution (VT) in whole brain was numerically higher compared with the BM regions. After a single oral osimertinib 80 mg dose, there was no consistent decrease in VT in whole brain or BMs. After greater than or equal to 21 days' daily treatment, VT in whole brain and BMs were numerically higher versus baseline. MRI revealed 56%–95% reduction in total BMs volume after 25–35 days of osimertinib 80 mg q.d. treatment. The [11C]osimertinib crossed the blood–brain and brain‐tumor barriers and had a high, homogeneous brain distribution in patients with EGFRm NSCLC and BMs.

Published
2023
Full Text
View/download PDF

2. Radiosynthesis and Evaluation of 11C-Labeled Isoindolone-Based Positive Allosteric Modulators for Positron Emission Tomography Imaging of Metabotropic Glutamate Receptor 2.

Author

Li, Yinlong, Dahl, Kenneth, Johnström, Peter, Varnäs, Katarina, Farde, Lars, Halldin, Christer, Medd, Amy, Maier, Donna, Powell, Mark E., Chen, Jiahui, Van, Richard, Patel, Jimmy, Chaudhary, Ahmad, Gao, Yabiao, Song, Zhendong, Haider, Ahmed, Shao, Yihan, Elmore, Charles S., Liang, Steven, and Schou, Magnus

Published
2024
Full Text
View/download PDF

3. P014 First-time-in-human visualisation of CCR9 expression in the gut by positron emission tomography

Author

MacKay, J, primary, Jucaite, A, additional, Cselényi, Z, additional, Johnström, P, additional, Dahl, K, additional, Schou, M, additional, Stenkrona, P, additional, Sousa, V, additional, Cortes Gonzalez, M, additional, Giffen, P, additional, Bouma, G, additional, Nys, J, additional, Brülls, M, additional, Duncan, M, additional, Larsson, J, additional, Lundahl, A, additional, Les, K, additional, Bergare, J, additional, Elmore, C, additional, Kiraga, J, additional, Blé, F X, additional, Fowler, A, additional, Belvisi, M, additional, and Marks, D, additional

Published
2024
Full Text
View/download PDF

4. Quantification and reliability of [11C]VC - 002 binding to muscarinic acetylcholine receptors in the human lung — a test-retest PET study in control subjects

Author

Zsolt Cselényi, Aurelija Jucaite, Cecilia Kristensson, Per Stenkrona, Pär Ewing, Andrea Varrone, Peter Johnström, Magnus Schou, Ana Vazquez-Romero, Mohammad Mahdi Moein, Martin Bolin, Jonathan Siikanen, Pär Grybäck, Bengt Larsson, Christer Halldin, Ken Grime, Ulf G. Eriksson, and Lars Farde

Subjects
Muscarinic acetylcholine receptors, Positron emission tomography, [11C]VC-002, Test-retest, Lungs, Medical physics. Medical radiology. Nuclear medicine, R895-920
Abstract

Abstract Background The radioligand [11C]VC-002 was introduced in a small initial study long ago for imaging of muscarinic acetylcholine receptors (mAChRs) in human lungs using positron emission tomography (PET). The objectives of the present study in control subjects were to advance the methodology for quantification of [11C]VC-002 binding in lung and to examine the reliability using a test-retest paradigm. This work constituted a self-standing preparatory step in a larger clinical trial aiming at estimating mAChR occupancy in the human lungs following inhalation of mAChR antagonists. Methods PET measurements using [11C]VC-002 and the GE Discovery 710 PET/CT system were performed in seven control subjects at two separate occasions, 2–19 days apart. One subject discontinued the study after the first measurement. Radioligand binding to mAChRs in lung was quantified using an image-derived arterial input function. The total distribution volume (V T) values were obtained on a regional and voxel-by-voxel basis. Kinetic one-tissue and two-tissue compartment models (1TCM, 2TCM), analysis based on linearization of the compartment models (multilinear Logan) and image analysis by data-driven estimation of parametric images based on compartmental theory (DEPICT) were applied. The test-retest repeatability of V T estimates was evaluated by absolute variability (VAR) and intraclass correlation coefficients (ICCs). Results The 1TCM was the statistically preferred model for description of [11C]VC-002 binding in the lungs. Low VAR (< 10%) across analysis methods indicated good reliability of the PET measurements. The V T estimates were stable after 60 min. Conclusions The kinetic behaviour and good repeatability of [11C]VC-002 as well as the novel lung image analysis methodology support its application in applied studies on drug-induced mAChR receptor occupancy and the pathophysiology of pulmonary disorders. Trial registration ClinicalTrials.gov identifier: NCT03097380 , registered: 31 March 2017.

Published
2020
Full Text
View/download PDF

5. The development of a GPR44 targeting radioligand [11C]AZ12204657 for in vivo assessment of beta cell mass

Author

Mahabuba Jahan, Peter Johnström, Ram K. Selvaraju, Marie Svedberg, Maria Sörhede Winzell, Jenny Bernström, Lee Kingston, Magnus Schou, Zhisheng Jia, Stanko Skrtic, Lars Johansson, Olle Korsgren, Lars Farde, Christer Halldin, and Olof Eriksson

Subjects
G-protein-coupled receptor 44 (GPR44), Beta cell imaging, Islet imaging, Beta cell mass, Diabetes, Medical physics. Medical radiology. Nuclear medicine, R895-920
Abstract

Abstract Background The G-protein-coupled receptor 44 (GPR44) is a beta cell-restricted target that may serve as a marker for beta cell mass (BCM) given the development of a suitable PET ligand. Methods The binding characteristics of the selected candidate, AZ12204657, at human GPR44 were determined using in vitro ligand binding assays. AZ12204657 was radiolabeled using 11C- or 3H-labeled methyl iodide ([11C/3H]CH3I) in one step, and the conversion of [11C/3H]CH3I to the radiolabeled product [11C/3H]AZ12204657 was quantitative. The specificity of radioligand binding to GPR44 and the selectivity for beta cells were evaluated by in vitro binding studies on pancreatic sections from human and non-human primates as well as on homogenates from endocrine and exocrine pancreatic compartments. Results The radiochemical purity of the resulting radioligand [11C]AZ12204657 was > 98%, with high molar activity (MA), 1351 ± 575 GBq/μmol (n = 18). The radiochemical purity of [3H]AZ12204657 was > 99% with MA of 2 GBq/μmol. Pancreatic binding of [11C/3H]AZ12204657 was co-localized with insulin-positive islets of Langerhans in non-diabetic individuals and individuals with type 2 diabetes (T2D). The binding of [11C]AZ12204657 to GPR44 was > 10 times higher in islet homogenates compared to exocrine homogenates. In human islets of Langerhans GPR44 was co-expressed with insulin, but not glucagon as assessed by co-staining and confocal microscopy. Conclusion We radiolabeled [11C]AZ12204657, a potential PET radioligand for the beta cell-restricted protein GPR44. In vitro evaluation demonstrated that [3H]AZ12204657 and [11C]AZ12204657 selectively target pancreatic beta cells. [11C]AZ12204657 has promising properties as a marker for human BCM.

Published
2018
Full Text
View/download PDF

6. Quantification and reliability of [11C]VC - 002 binding to muscarinic acetylcholine receptors in the human lung — a test-retest PET study in control subjects

Author

Cselényi, Zsolt, Jucaite, Aurelija, Kristensson, Cecilia, Stenkrona, Per, Ewing, Pär, Varrone, Andrea, Johnström, Peter, Schou, Magnus, Vazquez-Romero, Ana, Moein, Mohammad Mahdi, Bolin, Martin, Siikanen, Jonathan, Grybäck, Pär, Larsson, Bengt, Halldin, Christer, Grime, Ken, Eriksson, Ulf G., and Farde, Lars

Published
2020
Full Text
View/download PDF

7. Identification of Novel, Selective Ataxia-Telangiectasia Mutated Kinase Inhibitors with the Ability to Penetrate the Blood–Brain Barrier: The Discovery of AZD1390.

Author

Pike, Kurt G., Hunt, Thomas A., Barlaam, Bernard, Benstead, David, Cadogan, Elaine, Chen, Kan, Cook, Calum R., Colclough, Nicola, Deng, Chao, Durant, Stephen T., Eatherton, Andrew, Goldberg, Kristin, Johnström, Peter, Liu, Libin, Liu, Zhaoqun, Nissink, J. Willem M., Pang, Chengling, Pass, Martin, Robb, Graeme R., and Roberts, Caroline

Published
2024
Full Text
View/download PDF

10. 18th European Symposium on Radiopharmacy and Radiopharmaceuticals: Salzburg, Austria. 7-10 April 2016

Author

Radchenko, V., Engle, J. W., Roy, C., Griswold, J., Nortier, M. F., Birnbaum, E. R., Brugh, M., Mirzadeh, S., John, K. D., Fassbender, M. E., Zhai, Chuangyan, Franssen, Gerben M., Petrik, Milos, Laverman, Peter, Decristoforo, Clemens, Samia, Ait-Mohand, Véronique, Dumulon-Perreault, Brigitte, Guérin, Summer, D., Kroess, A., Rangger, C., Haas, H., Laverman, P., Gerben, F., von Guggenberg, E., Decristoforo, C., Bolzati, Cristina, Salvarese, Nicola, Refosco, Fiorenzo, Meléndez-Alafort, Laura, Carpanese, Debora, Rosato, Antonio, Saviano, Michele, Del Gatto, Annarita, Comegna, Daniela, Zaccaro, Laura, Billaud, Emilie, Ahamed, Muneer, Cleeren, Frederik, Shahbazali, Elnaz, Noël, Tim, Hessel, Volker, Verbruggen, Alfons, Bormans, Guy, Cleeren, F., Lecina, J., Koole, M., Verbruggen, A., Bormans, G., Lugatoa, B., Stucchia, S., Turollaa, E. A., Giulianoa, L., Toddea, S., Ferraboschib, P., Klok, R. P., Mooijer, M. P. J., Hendrikse, N. H., Windhorst, A. D., Collet, C., Petry, N., Chrétien, F., Karcher, G., Pellegrini-Moïse, N., Lamandé-Langle, S., Pfaff, Sarah, Philippe, Cecile, Mitterhauser, Markus, Hacker, Marcus, Wadsak, Wolfgang, Guérard, François, Lee, Yong-Sok, Gouard, Sébastien, Baidoo, Kwamena, Alliot, Cyrille, Chérel, Michel, Brechbiel, Martin W., Gestin, Jean-François, Lam, K., Chan, C., Reilly, R. M., Paillas, Salomé, Marshall, John, Pouget, Jean-Pierre, Sosabowski, Jane, Briard, Emmanuelle, Auberson, Yves P., Reilly, John, Healy, Mark, Sykes, David, Paulus, Andreas, Lichtenbelt, Wouter van Marken, Mottaghy, Felix, Bauwens, Matthias, Baranski, Ann-Christin, Schäfer, Martin, Bauder-Wüst, Ulrike, Haberkorn, Uwe, Eder, Matthias, Kopka, Klaus, Chaussard, M., Hosten, B., Vignal, N., Tsoupko-Sitnikov, V., Hernio, N., Hontonnou, F., Merlet, P., Poyet, J. L., Sarda-Mantel, L., Rizzo-Padoin, N., Cardinale, J., Schäfer, M., Benešová, M., Bauder-Wüst, U., Seibert, O., Giesel, F., Haberkorn, U., Eder, M., Kopka, K., Nematallah, Mansour, Michel, Paquette, Samia, Ait-Mohand, Véronique, Dumulon-Perreault, Roger, Lecomte, Brigitte, Guérin, Fernandez-Maza, L., Rivera-Marrero, S., Capote, A. Prats, Parrado-Gallego, A., Fernandez-Gomez, I., Balcerzyk, M., Sablon-Carrazana, M., Perera-Pintado, A., Merceron-Martinez, D., Acosta-Medina, E., Rodriguez-Tanty, C., Attili, Bala, Ahamed, Muneer, Bormans, Guy, Philippe, C., Zeilinger, M., Scherer, T., Fürnsinn, C., Dumanic, M., Wadsak, W., Hacker, M., Mitterhauser, M., Janssen, B., Vugts, D. J., Molenaar, G.T. T., Funke, U., Kruijer, P. S., Dollé, F., Bormans, G., Lammertsma, A. A., Windhorst, A. D., Vermeulen, Koen, Ahamed, Muneer, Schnekenburger, Michael, Froeyen, Mathy, Olberg, Dag Erlend, Diederich, Marc, Bormansa, Guy, Raaphorst, R. M., Luurtsema, G., Lammertsma, A. A., Elsinga, P. H., Windhorst, A D., Rotteveel, Lonneke, Funke, Uta, ten Dijke, Peter, Bogaard, Harm Jan, Lammertsma, Adriaan A., Windhorst, Albert D., Song, Lei, Able, Sarah, Falzone, Nadia, Kersemans, Veerle, Vallis, Katherine, Carta, Davide, Salvarese, Nicola, Sihver, Wiebke, Gao, Feng, Pietzsch, Hans Jürgen, Biondi, Barbara, Ruzza, Paolo, Refosco, Fiorenzo, Bolzati, Cristina, Haubner, Roland, Finkensted, Armin, Stegmair, Armin, Rangger, Christine, Decristoforo, Clemens, Zoller, Heinz, Virgolini, Irene J., Pooters, Ivo, Lotz, Maartje, Wierts, Roel, Mottaghy, Felix, Bauwens, Matthias, Forsback, Sarita, Jörgen, Bergman, Riikka, Kivelä, Karageorgou, M., Radović, M., Tsoukalas, C., Antic, B., Gazouli, M., Paravatou-Petsotas, M., Xanthopouls, S., Calamiotou, M., Stamopoulos, D., Vranješ-Durić, S., Bouziotis, P., Lunev, A. S., Larenkov, A. A., Petrosova, K. A., Klementyeva, O. E., Kodina, G. E., Kvernenes, O. H., Adamsen, T. C. H., Martin, René, Weidlich, Sebastian, Zerges, Anna-Maria, Gameiro, Cristiana, Lazarova, Neva, Müllera, Marco, Luurtsema, Gert, de Vries, Michèl, Ghyoot, Michel, van der Woude, Gina, Zijlma, Rolf, Dierckx, Rudi, Boersma, Hendrikus H., Elsinga, Philip H., Lambrecht, Fatma Yurt, Er, Ozge, Ince, Mine, Avci, Cıgır Biray, Gunduz, Cumhur, Sarı, Fatma Aslihan, Ocakoglu, Kasim, Er, Ozge, Ersoz, Onur Alp, Lambrecht, Fatma Yurt, Ince, Mine, Kayabasi, Cagla, Gunduz, Cumhur, Kniess, Torsten, Meister, Sebastian, Fischer, Steffen, Steinbach, Jörg, Ashfaq, Rabia, Iqbal, Saeed, ullah Khan, Irfan, Iglesias-Jerez, R., Martín-Banderas, L., Perera-Pintado, A., Borrego-Dorado, I., Farinha-Antunes, Ines, Kwizera, Chantal, Lacivita, Enza, Lucente, Ermelinda, Niso, Mauro, De Giorgio, Paola, Perrone, Roberto, Colabufo, Nicola A., Elsinga, Philip H., Leopoldo, Marcello, Vaulina, V. V., Fedorova, O. S., Orlovskaja, V. V., Chen, С. L., Li, G. Y., Meng, F. C., Liu, R. S., Wang, H. E., Krasikova, R. N., Meléndez-Alafort, Laura, Abozeid, Mohamed, Ferro-Flores, Guillermina, Negri, Anna, Bello, Michele, Uzunov, Nikolay, Paiusco, Martha, Esposito, Juan, Rosato, Antonio, Meléndez-Alafort, Laura, Bolzati, Cristina, Ferro-Flores, Guillermina, Salvarese, Nicola, Carpanese, Debora, Abozeid, Mohamed, Rosato, Antonio, Uzunov, Nikolay, Palmieri, L., Verbrugghen, T., Glassner, M., Hoogenboom, R., Staelens, S., Wyffels, L., Orlovskaja, V. V., Kuznetsova, O. F., Fedorova, O. S., Maleev, V. I., Belokon, Yu. N., Geolchanyan, A., Saghyan, A. S., Mu, L., Schibli, R., Ametamey, S. M., Krasikova, R. N., Revunov, Evgeny, Malmquist, Jonas, Johnström, Peter, Van Valkenburgh, Juno, Steele, Dalton, Halldin, Christer, Schou, Magnus, Osati, Samira, Paquette, Michel, Beaudoin, Simon, Ali, Hasrat, Guerin, Brigitte, Leyton, Jeffrey V., van Lier, Johan E., Di Iorio, V, Iori, M., Donati, C., Lanzetta, V., Capponi, P. C., Rubagotti, S., Dreger, T., Kunkel, F., Asti, M., Zhai, Chuangyan, Rangger, Christine, Summer, Dominik, Haas, Hubertus, Decristoforo, Clemens, Kijprayoon, Suphansa, Ruangma, Ananya, Ngokpol, Suthatip, Tuamputsha, Samart, Filp, Ulrike, Pees, Anna, Taddei, Carlotta, Pekošak, Aleksandra, Gee, Antony D., Poot, Alex J., Windhorst, Albert D., Gunay, Mine Silindir, Ozer, A. Yekta, Erdogan, Suna, Baysal, Ipek, Guilloteau, Denis, Chalon, Sylvie, Galli, Filippo, Artico, Marco, Taurone, Samanta, Bianchi, Enrica, Weintraub, Bruce D., Skudlinski, Mariusz, Signore, Alberto, Lepareur, Nicolas, Noiret, Nicolas, Hindré, François, Lacœuille, Franck, Benoist, Eric, Garin, Etienne, Trejo-Ballado, F., Zamora-Romo, E., Manrique-Arias, J. C., Gama-Romero, H M, Contreras-Castañon, G., Tecuapetla-Chantes, R. G., Avila-Rodriguez, M. A., Kvaternik, H., Hausberger, D., Zink, C., Rumpf, B., Aigner, R. M., Kvaternik, H., Hausberger, D., Rumpf, B., Aigner, R. M., Janković, Drina, Lakić, Mladen, Savić, Aleksandar, Ristić, Slavica, Nikolić, Nadežda, Vukadinović, Aleksandar, Sabo, Tibor J., Vranješ-Đurić, Sanja, Vranješ-Đurić, S., Radović, M., Janković, D., Nikolić, N., Goya, G. F., Calatayud, P., Spasojević, V., Antić, B., Goblet, David, Gameiro, Cristiana, Lazarova, Neva, Gameiro, Cristiana, Oxley, Ian, Abrunhosa, Antero, Kramer, Vasko, Vosjan, Maria, Spaans, Arnold, Vats, Kusum, Satpati, Drishty, Sarma, Haladhar D., Banerjee, Sharmila, Wojdowska, W., Pawlak, D. W., Parus, L. J., Garnuszek, P., Mikołajczak, R., Pijarowska-Kruszyna, J., Jaron, A., Kachniarz, A., Malkowski, B., Garnuszek, P., Mikolajczak, R., Ilem-Ozdemir, Derya, Caglayan-Orumlu, Oya, Asikoglu, Makbule, Ilem-Ozdemir, Derya, Caglayan-Orumlu, Oya, Asikoglu, Makbule, Eveliina, Arponen, Semi, Helin, Timo, Saarinen, Simo, Vauhkala, Esa, Kokkomäki, Pertti, Lehikoinen, De Simone, Mariarosaria, Pascali, Giancarlo, Carzoli, Ludovica, Quaglierini, Mauro, Telleschi, Mauro, Salvadori, Piero A., Lam, Phoebe, Aistleitner, Martina, Eichinger, Reinhard, Artner, Christoph, Nakka, Surendra, MC, Hemantha Kumara, Al-Qahtani, Mohammed, Al-Qahtani, Mohammed, Al-Malki, Yousif, Mambilima, N., Rubow, S. M., Berroterán-Infante, N., Hacker, M., Mitterhauser, M., Wadsak, W., Funke, Uta, Cleeren, Frederik, Lecina, Joan, Gallardo, Rodrigo, Verbruggen, Alfons M., Bormans, Guy, Ramos-Membrive, Rocío, Brotons, Ana, Quincoces, Gemma, Inchaurraga, Laura, de Redín, Inés Luis, Morán, Verónica, García-García, Berta, Irache, Juan Manuel, Peñuelas, Iván, Trabelsi, M., Cooper, M. S., Abella, Alejandra, Fuente, Teodomiro, Montellano, Antonio Jesús, Martínez, Teresa, Rabadan, Ruben, Meseguer-Olmo, Luis, Lehtiniemi, P., Yim, C., Mikkola, K., Nuutila, P., Solin, O., von Guggenberg, E., Rangger, C., Mair, C., Balogh, L., Pöstényi, Z., Pawlak, D., Mikołajczak, R., Socan, A., Peitl, P. Kolenc, Krošelj, M., Rangger, C., Decristoforo, C., Collet, C., Remy, S., Didier, R., Vergote, T., Karcher, G., Véran, N., Pawlak, D., Maurin, M., Garnuszek, P., Karczmarczyk, U., Mikołajczak, R., Fredericia, Pil, Severin, Gregory, Groesser, Torsten, Köster, Ulli, Jensen, Mikael, Leonte, R., Puicea, F. D., Raicu, A., Min, E. A., Serban, R., Manda, G., Niculae, D., Zerna, Marion, Schieferstein, Hanno, Müller, Andre, Berndt, Mathias, Yim, Cheng-Bin, Mikkola, Kirsi, Nuutila, Pirjo, Solin, Olof, Seifert, D., Ráliš, J., Lebeda, O., Selivanova, Svetlana V., Senta, Helena, Lavallée, Éric, Caouette, Lyne, Turcotte, Éric, Lecomte, Roger, Kochovska, Marina Zdraveska, Ivanovska, Emilija Janjevik, Jokic, Vesna Spasic, Ackova, Darinka Gjorgieva, Smilkov, Katarina, Makreski, Petre, Stafilov, Trajče, Janevik-Ivanovska, Emilija, Alemu, Aschalew, Muchira, Joel Munene, Wanjeh, David Mwanza, Janevik-Ivanovska, Emilija, Janevik-Ivanovska, Emilija, Zdravev, Zoran, Bhonsle, Uday, Alberto, Osso Júnior João, Duatti, Adriano, Angelovska, Bistra, Stojanovska, Zdenka, Sarafinovska, Zorica Arsova, Bosnakovski, Darko, Gorgieva-Ackova, Darinka, Smilkov, Katarina, Drakalska, Elena, Venkatesh, Meera, Gulaboski, Rubin, Colin, Didier J., Inkster, James A. H., Germain, Stéphane, Seimbille, Yann, Atiq-ur-Rehman, and Cayero-Otero

Published
2016
Full Text
View/download PDF

17. Sa2018 FIRST-TIME-IN-HUMAN VISUALISATION OF CCR9 EXPRESSION IN THE GUT BY POSITRON EMISSION TOMOGRAPHY.

Author

MacKay, James, Jucaite, Aurelija, Cselényi, Zsolt, Johnström, Peter, Dahl, Kenneth, Schou, Magnus, Stenkrona, Per, Sousa, Vasco C., Högnäsbacka, Antonia, Gonzalez, Miguel A. Cortes, Giffen, Paul, Bouma, Gerben, Nys, Josquin, Brülls, Mikael, Duncan, Marnie, Larsson, Julia, Lundahl, Anna, Les, Karolina A., Bergare, Jonas, and Elmore, Charles S.

Published
2024
Full Text
View/download PDF

18. P2.14-33 An Open-Label PET-MRI Study to Determine Brain Exposure of Osimertinib in Patients with EGFR Mutant NSCLC and CNS Metastases

Author

Ekman, S., primary, Varrone, A., additional, Jucaite, A., additional, Vishwanathan, K., additional, Brown, A., additional, Cselényi, Z., additional, Martin, H., additional, Lewensohn, R., additional, Schou, M., additional, Laus, G., additional, Van Der Aart, J., additional, Johnström, P., additional, Singh, N., additional, and Farde, L., additional

Published
2019
Full Text
View/download PDF

19. Preclinical comparison of the blood brain barrier (BBB) permeability of osimertinib (AZD9291) with other irreversible next generation EGFR TKIs

Author

Colclough, N., primary, Ballard, P.G., additional, Barton, P., additional, Chen, K., additional, Cross, D.A.E., additional, Finlay, M.R.V., additional, Han, L., additional, Janefeldt, A., additional, Johnström, P., additional, Ward, R.A., additional, Wrigley, G.L., additional, Yan, Y., additional, Yates, J.W.T., additional, Zhang, D., additional, and Zhang, Z., additional

Published
2016
Full Text
View/download PDF

20. Integrated strategy for use of positron emission tomography in nonhuman primates to confirm multitarget occupancy of novel psychotropic drugs : An example with AZD3676

Author

Varnäs, K., Juréus, A., Johnström, P., Ahlgren, C., Schött, Pär, Schou, M., Gruber, S., Jerning, E., Malmborg, J., Halldin, C., Afzelius, L., Farde, L., Varnäs, K., Juréus, A., Johnström, P., Ahlgren, C., Schött, Pär, Schou, M., Gruber, S., Jerning, E., Malmborg, J., Halldin, C., Afzelius, L., and Farde, L.

Abstract

Positron emission tomography (PET) is widely applied in central nervous system (CNS) drug development for assessment of target engagement in vivo. As the majority of PET investigations have addressed drug interaction at a single binding site, findings of multitarget engagement have been less frequently reported and have often been inconsistent with results obtained in vitro. AZD3676 [N,N-dimethyl-7-(4-(2-(pyridin-2-yl)ethyl)piperazin-1-yl) benzofuran-2-carboxamide] is a novel combined serotonin (5- hydroxytryptamine) 5-HT1A and 5-HT1B receptor antagonist that was developed for the treatment of cognitive impairment in Alzheimer's disease. Here, we evaluated the properties of AZD3676 as a CNS drug by combining in vitro and ex vivo radioligand binding techniques, behavioral pharmacology in rodents, and PET imaging in nonhuman primates. Target engagement in the nonhuman primate brain was assessed in PET studies by determination of drug-induced occupancy using receptorselective radioligands. AZD3676 showed preclinical properties consistent with CNS drug potential, including nanomolar receptor affinity and efficacy in rodent models of learning and memory. In PET studies of the monkey brain, AZD3676 inhibited radioligand binding in a dose-dependent manner with similar affinity at both receptors. The equally high affinity at 5-HT1A and 5-HT1B receptors as determined in vivo was not predicted from corresponding estimates obtained in vitro, suggestingmore than 10-fold selectivity for 5-HT1A versus 5-HT1B receptors. These findings support the further integrated use of PET for confirmation of multitarget occupancy of CNS drugs. Importantly, earlier introduction of PET studies in nonhuman primates may reduce future development costs and the requirement for animal experiments in preclinical CNS drug development programs., QC 20161207

Published
2016
Full Text
View/download PDF

26. 145. Translocator protein (TSPO) as a biomarker of microglia activation: PET imaging using [11C]PBR28 in Parkinson’s disease

Author

Jucaite, A., primary, Cselényi, Z., additional, Varrone, A., additional, Varnäs, K., additional, Johnström, P., additional, Halldin, C., additional, Salter, H., additional, McLoughlin, M.J., additional, Rinne, J., additional, Svenningsson, P., additional, Alexander, R., additional, Kugler, A., additional, and Farde, L., additional

Published
2013
Full Text
View/download PDF

29. Discovery of AZD4747, a Potent and Selective Inhibitor of Mutant GTPase KRASG12Cwith Demonstrable CNS Penetration

Author

Kettle, Jason G., Bagal, Sharan K., Barratt, Derek, Bodnarchuk, Michael S., Boyd, Scott, Braybrooke, Erin, Breed, Jason, Cassar, Doyle J., Cosulich, Sabina, Davies, Michael, Davies, Nichola L., Deng, Chao, Eatherton, Andrew, Evans, Laura, Feron, Lyman J., Fillery, Shaun, Gleave, Emma S., Goldberg, Frederick W., Cortés González, Miguel A., Guerot, Carine, Haider, Afreen, Harlfinger, Stephanie, Howells, Rachel, Jackson, Anne, Johnström, Peter, Kemmitt, Paul D., Koers, Alex, Kondrashov, Mikhail, Lamont, Gillian M., Lamont, Scott, Lewis, Hilary J., Liu, Libin, Mylrea, Megan, Nash, Samuel, Niedbala, Michael J., Peter, Alison, Phillips, Christopher, Pike, Kurt, Raubo, Piotr, Robb, Graeme R., Ross, Sarah, Sanders, Matthew G., Schou, Magnus, Simpson, Iain, and Steward, Oliver

Abstract

The glycine to cysteine mutation at codon 12 of Kirsten rat sarcoma (KRAS) represents an Achilles heel that has now rendered this important GTPase druggable. Herein, we report our structure-based drug design approach that led to the identification of 14, AZD4747, a clinical development candidate for the treatment of KRASG12C-positive tumors, including the treatment of central nervous system (CNS) metastases. Building on our earlier discovery of C5-tethered quinazoline AZD4625, excision of a usually critical pyrimidine ring yielded a weak but brain-penetrant start point which was optimized for potency and DMPK. Key design principles and measured parameters that give high confidence in CNS exposure are discussed. During optimization, divergence between rodent and non-rodent species was observed in CNS exposure, with primate PET studies ultimately giving high confidence in the expected translation to patients. AZD4747 is a highly potent and selective inhibitor of KRASG12Cwith an anticipated low clearance and high oral bioavailability profile in humans.

Published
2023
Full Text
View/download PDF

31. Dynamic In Vivo Imaging of Receptors in Small Animals Using Positron Emission Tomography.

Author

Walker, John M., Johnström, Peter, Fryer, Tim D., Richards, Hugh K., Barret, Olivier, and Davenport, Anthony P.

Abstract

Positron emission tomography (PET) is a functional imaging technique that is used to study biological processes in vivo. Data obtained in a PET scan can provide information regarding tissue physiology or pathophysiology, as well as pharmacokinetic and pharmacodynamic information. It is the most sensitive technique available to image and quantify receptor distributions in vivo, and it has been used extensively to study major neurotransmitter systems such as the dopamine, serotonin, benzodiazepine, opiate, and cholinergic systems (1). Over the years, PET has increasingly been recognized as a very powerful tool to accelerate development and assessment of existing and novel drugs (6-7). [ABSTRACT FROM AUTHOR]

Published
2005
Full Text
View/download PDF

32. Imaging and Characterization of Radioligands for Positron Emission Tomography Using Quantitative Phosphor Imaging Autoradiography.

Author

Walker, John M., JohnstrÖm, Peter, and Davenport, Anthony P.

Abstract

Quantification of radioligand binding by exposing labeled tissue sections to phosphor screens in cassettes is similar to autoradiography using radiation sensitive film (1) (see Chapters 5 and 77}). The major advantage of phosphor screens over film is the greatly increased sensitivity with exposure times reduced by at least one order of magnitude (2,3). This is essential for short-lived radionuclides—such as (su18)F and (su11)1C, with half-lives of 109.8 and 20.4 min, respectively—that are used to label peptide or drug ligands to image receptors noninvasively in vivo by positron emission tomography (PET) (see Chapter 11). Phosphor imaging can also considerably reduce exposure times for weak β-particle emitters such as (su3)H from months to days (3). A second advantage is the increased linear dynamic range of five orders of magnitude (2,3). This increased dynamic range makes it less likely that screens will be saturated. This is important for PET radioligands in which, owing to the short half-life of the radionuclide, it is only possible to image once, whereas re-exposure is possible for isotopes with longer half-lives. [ABSTRACT FROM AUTHOR]

Published
2005
Full Text
View/download PDF

36. The labelling of 2-oxoquazepam with electrophilic 18F

Author

Duelfer, T., primary, Johnström, P., additional, Stone-Elander, S., additional, Holland, A., additional, Halldin, C., additional, Haaparanta, M., additional, Solin, O., additional, Bergman, J., additional, Steinman, M., additional, and Sedvall, G., additional

Published
1991
Full Text
View/download PDF

39. The normal pituitary examined with positron emission tomography and (methyl-C)-L-methionine and (methyl-C)-D-methionine.

Author

Bergström, M., Muhr, C., Ericson, K., Lundqvist, H., Lilja, A., Eriksson, L., Blomquist, G., Långström, B., and Johnström, P.

Abstract

Four patients with radiologically normal pituitary gland were examined with positron emission tomography after the administration of (methyl-C)-L-methionine. On a following day the examination was repeated with (methyl-c)-D-methionine. The accumulation rate of L-methionine in the pituitary was measured, giving a value that was about twice that of normal brain tissue. The accumulation rate of D-methionine in the pituitary was almost a factor of 10 lower than that of L-methionine. In the normal brain tissue that ratio was 2.3. The study clearly indicates that the methionine uptake in the pituitary is stereospecific. C-D-methionine is freely distributed in the tissue without entrapment, whereas C-L-methionine is irreversibly bound. It is concluded that PET with C-L-methionine can be used to study amino acid utilization in the pituitary. [ABSTRACT FROM AUTHOR]

Published
1987
Full Text
View/download PDF

41. In Vivo Imaging of Cardiovascular Endothelin Receptors Using the Novel Radiolabelled Antagonist [18F]-SB209670 and Positron Emission Tomography (microPET)

Author

Johnström, Peter, Fryer, Tim D., Richards, Hugh K., Barret, Olivier, Clark, John C., Ohlstein, Eliot H., Pickard, John D., and Davenport, Anthony P.

Abstract

The aim of this study was to develop an 18F-labelled analogue of SB209670 with subnanomolar affinity for the endothelin receptor and to test whether it would have the required pharmacokinetic properties to permit binding and imaging of endothelin receptors in rat heart in vivo using small animal positron emission tomography (PET) imaging. [18F]-SB209670 could be produced in a total radiochemical yield of 14.9 ± 3.8% in 162 ± 7 minutes (n = 6). The radiochemical purity of the isolated radioligand was 99% and the specific activity was 100-150 GBq/μmol. In vitro characterization using ligand-binding assays demonstrated that [18F]-SB209670 bound with a single subnanomolar affinity to human heart tissue (n = 3) with a KD= 0.67 ± 0.14 nMand a Bmax = 168.3 ± 29.3 fmol/mg protein. The binding was time-dependent with a half-time (t½) for association of 3.8 minutes and an association rate constant (kobs) of 0.182 ± 0.032/min. In vivo distribution in the rat was studied using microPET. Dynamic imaging revealed a fast clearance of [18F]-SB209670 from the circulation by the liver, indicative of a high degree of metabolism. However, visualization of uptake in the rat heart was achievable and dynamic PET data together with the in vitro results suggest that [18F]-SB209670 binds rapidly and primarily to endothelin-A receptors in the heart.

Published
2004
Full Text
View/download PDF

42. Abstracts of the 12th IIS (UK Group) Symposium

Author

Staunton, J, Gates, Paul, Kearney, Gordon, Fonseca, Tatiana, Anderson, J.C., Broughton, S., Glaser, M., Booker-Milburn, Kevin I., Caroll, M. A., Rzepa, H. S., Pike, V. W., Widdowson, D. A., Ellames, George J., Gibson, Jennifer S., Herbert, John M., Smith, David I., Wilkinson, D J, Mather, A N, Hickey, M J, Kingston, L P, Lockley, W J S, Hollis, Stephen, Johnston, Grant, Bloom, A. Jon, Johnström, Peter, and Davenport, Anthony P.

Abstract

“Synthesis & Application of Labelled Compounds 2002” Isotopes and Mass Spectrometry Carbon-13 Labelling to Aid the Development of the Catalytic Alkenation of Carbonyls Production and Applications of 124I for Positron Emission Tomography Organic Photochemistry: Synthetic Approaches to Alkaloids in a Reagentless Environment Fluorinaion for Positron Emission Tomography Synthetic Consequences of Kinetic Isotopes Effects: Synthesis of [13 C6]-SR31742A For Human Trail Purposes Tritio-Dehalogenation: New Variants on an Old Theme The Synthesis of BOC-L-Proline-[14C2] Benzyl Ester Peptide Labelling with Fluorine-18

Published
2003
Full Text
View/download PDF

43. 18F-Endothelin-1, a positron emission tomography (PET) radioligand for the endothelin receptor system: radiosynthesis and in vivo imaging using microPET

Author

JOHNSTRÖM, Peter, HARRIS, Neil G., FRYER, Tim D., BARRET, Olivier, CLARK, John C., PICKARD, John D., and DAVENPORT, Anthony P.

Abstract

Positron emission tomography (PET) is a powerful technique with the sensitivity to image and quantify receptor-bound radioligands in vivo. Recent progress in PET scanner technology has resulted in the development of dedicated tomographs designed for small animals, with resolution that allows the delineation of discrete organs and their larger substructures in rats and mice. Our aim was to determine whether endothelin-1 (ET-1) could be labelled with 18F, and whether the resulting 18F-ET-1 would have the required pharmacokinetic properties to permit binding and imaging of ET receptors in vivo. 18F-ET-1 could be produced in a total radiochemical yield of 5.9±0.7% in 207±3min (n = 20). Specific radioactivities were in the range 220–370GBq/µmol, and the radiochemical purity of the isolated 18F-ET-1 was >95%. In vivo distribution in the rat was studied using microPET. High levels of 18F-ET-1 uptake were found in lung and kidney, whereas liver showed moderate levels of uptake. The resolution of the microPET scanner was sufficient to differentiate heterogeneous uptake in subrenal structures in the rat.

Published
2002
Full Text
View/download PDF

44. Labeling of human C-peptide by conjugation with <TOGGLE>N</TOGGLE>-succinimidyl-4-[<SUP>18</SUP>F]fluorobenzoate

Author

Fredriksson, Anna, Johnström, Peter, Stone-Elander, Sharon, Jonasson, Per, Nygren, Per-Åke, Ekberg, Karin, Johansson, Bo-Lennart, and Wahren, John

Abstract

We have labeled proinsulin connecting peptide (C-peptide) with fluorine-18 (t½=109.7 min) in order to perform in vivo biodistribution and pharmacokinetic studies with position emission tomography (PET). This study reports the optimization of the conjugation labeling in the N-terminal with N-succinimidyl-4-[18F]fluorobenzoate ([18F]SFB). In preparative runs N-4-[18F]fluorobenzoyl-C-peptide ([18F]FB-C-peptide) was produced in 8–12% decay-corrected yields, counted from resolubilized [18F]F−, in less than 5 h. The specific radioactivity of [18F]FB-C-peptide, determined using ELISA for one of the preparations, was around 70 GBq/μmol at end of synthesis. Copyright © 2001 John Wiley & Sons, Ltd.

Published
2001

45. Synthesis of [methoxy-<SUP>11</SUP>C]PD153035, a selective EGF receptor tyrosine kinase inhibitor

Author

Johnström, Peter and Fredriksson, Anna

Abstract

[Methoxy-11C]PD153035, a potent and specific inhibitor of the EGF receptor tyrosine kinase, was prepared by O-alkylation of O-desmethyl PD153035 with [11C]methyl iodide in DMF. The radiochemical incorporation of [11C]CH3I was on the order of 45%. The mean specific activity obtained at end-of-synthesis (EOS) was 26 GBq/μmol (n=3; range 20–36 GBq/μmol) and total synthesis time was 45–50 minutes including formulation. © 1998 John Wiley & Sons, Ltd.

Published
1998
Full Text
View/download PDF

46. PET Study of Methionine Accumulation in Glioma and Normal Brain Tissue

Author

Bergström, Mats, Ericson, Kaj, Hagenfeldt, Lars, Mosskin, Mikael, von Holst, Hans, Norén, Georg, Eriksson, Lars, Ehrin, Erling, and Johnström, Peter

Abstract

Five patients with glioma were examined with positron emission tomography using ([11C]methyl)-L-methionine. The study was repeated while the patient was being infused with branched chain amino acids (BCAA), 250 μmol/min. The accumulation rates of methionine in tumor tissue and in normal brain tissue were compared without and with the infusion of amino acids. Both tumor tissue and normal brain tissue showed a reduction in the methionine accumulation by 35 while the patient received the infusion. In one patient with a severe blood-tissue barrier disruption the tumor accumulation rate was unaffected. It is concluded that in gliomas without severe blood-tissue barrier disruption, the accumulation of methionine is governed by processes exhibiting similar properties regarding competition with BCAA as in normal brain tissue.

Published
1987

47. Positron Emission Tomography Compared with Magnetic Resonance Imaging and Computed Tomography in Supratentorial Gliomas Using Multiple Stereotactic Biopsies as Reference

Author

Mosskin, M., Ericson, K., Hindmarsh, T., von Holst, H., Collins, V. P., Bergström, M., Eriksson, L., and Johnström, P.

Abstract

Ten patients with findings at computed tomography (CT) suggesting intracranial supratentorial glioma were investigated to compare the diagnostic efficacy of this technique with that of positron emission tomography (PET) using 11C-methionine and exminations with magnetic resonance (MR). The findings were related to histopathologic examination of serial stereotactic biopsies, which were guided by the appearance of the lesions on PET examination. To obtain corresponding slice orientation with the different examination techniques, an individually shaped helmet fixation was used. However, in 3 cases this fixation device could not be used for MR. Histopathologic diagnosis, obtained in all cases from multiple target stereotactic biopsies, included glioma in 9 patients and reactive gliosis in one case. A detailed comparison of the three imaging techniques and the findings at stereotactic biopsies was possible in 7 patients, while in 3 patients comparison with MR was less exact due to the patient's refusal to wear the helmet during this examination. MR was the most accurate method for outlining the total extent of a lesion, i.e. the tumor and the edema surrounding it. Four lesions had homogeneous signal characteristics and in 6 lesions two (or more) compartments could be distinguished with MR. In 5 cases the MR findings were in complete agreement with the histopathologic findings. However, a thorough correlation between signal characteristics and histology was not possible. Using PET the occurrence and the extent of tumor tissue was correctly predicted in 7 patients. The PET was normal in one case. Findings at CT were in agreement with the histopathologic diagnosis in 5 patients. MR was the most sensitive method for the detection of lesions. PET using methionine appeared to have a somewhat higher capacity to outline correctly the true extent of a tumor. The combination of CT and PET was superior to MR for determining the type and grade of the tumors.

Published
1989
Full Text
View/download PDF

48. The normal pituitary examined with positron emission tomography and (methyl-11C)-L-methionine and (methyl-11C)-D-methionine

Author

Bergström, M., Muhr, C., Ericson, K., Lundqvist, H., Lilja, A., Eriksson, L., Blomquist, G., Långström, B., and Johnström, P.

Abstract

Four patients with radiologically normal pituitary gland were examined with positron emission tomography after the administration of (methyl-11C)-L-methionine. On a following day the examination was repeated with (methyl-11c)-D-methionine. The accumulation rate of L-methionine in the pituitary was measured, giving a value that was about twice that of normal brain tissue. The accumulation rate of D-methionine in the pituitary was almost a factor of 10 lower than that of L-methionine. In the normal brain tissue that ratio was 2.3. The study clearly indicates that the methionine uptake in the pituitary is stereospecific. 11C-D-methionine is freely distributed in the tissue without entrapment, whereas 11C-L-methionine is irreversibly bound. It is concluded that PET with 11C-L-methionine can be used to study amino acid utilization in the pituitary.

Published
1987
Full Text
View/download PDF

49. Positron Emission Tomography with 11C-Methionine and Computed Tomography of Intracranial Tumours Compared with Histopathologic Examination of Multiple Biopsies

Author

Mosskin, M., von Holst, H., Bergström, M., Collins, V. P., Eriksson, L., Johnström, P., and Norén, G.

Abstract

A selected group of 36 patients with suspected supratentorial gliomas were investigated with positron emission tomography (PET) using 11C-methionine and transmission computed tomography (CT) before and after intravenous injection of contrast medium. Every examination was performed with the head fixed in a plastic helmet and a baseplate to guarantee that the slice orientation was the same at examinations with the two modalities and over time. Guided by the examinations, multiple stereotactic biopsies were performed with the biopsy instrument mounted on the baseplate. Regional accumulation of methionine was compared with histology of the corresponding samples and with attenuation before and after injection of contrast medium as well as mass effect on CT. Typically, there was a low attenuating lesion with a slight mass effect on CT. There was an increased accumulation compared with normal brain tissue in 31 cases of tumours and ordinary or decreased accumulation in 3 cases of tumours. In 22 cases with increased accumulation of methionine the extension of the tumour judged by PET corresponded with that of histology. In 4 cases tumour cells were found outside the area with pathologic methionine uptake. In 5 patients there were areas with increased methionine accumulation where no tumour cells were found. In 22 cases PET using methionine was more accurate than CT in defining the tumour boundaries as determined from the histologic findings. Four groups of biopsy specimens with different amounts of methionine accumulation are described. The uptake in a single biopsy gives good but not exact information about the histology of the specimen.

Published
1987
Full Text
View/download PDF

50. 11C-2-Deoxy-d-glucose: synthesis and preliminary comparison with 11C-d-glucose as a tracer for cerebral energy metabolism in PET studies

Author

Stone-Elander, Sharon, Nilsson, J. Lars G., Blomqvist, Gunnar, Ehrin, Erling, Eriksson, Lars, Garmelius, Birgit, Greitz, Torgny, Johnström, Peter, Sjögren, Irene, and Widén, Lennart

Abstract

11C-2-Deoxy-D-glucose has been prepared by the reaction of 11C-hydrogen cyanide with a stable precursor, 1-deoxy-2,3:4,5-di-O-isopropylidine-1-iodo-D-arabitol, thereby avoiding the synthesis of starting material immediately prior to labeling. Fast, efficient, and reproducible solvent change from dimethyl sulfoxide to ether by flash chromatography enabled the use of diisobutylaluminium hydride in the reduction of the intermediate nitrile. Hydrolysis of the imine-aluminum complex with sulfuric acid, removal of the isopropylidine protecting groups with formic acid, and HPLC purification with an Aminex HPX-87P column yielded 11C-2-deoxy-D-glucose in an aqueous solution, sterile, pyrogen-free, and ready for use in human studies. The radiochemical yield was ~20% after a synthesis time of 50 min. The 11C-2-deoxy-D-glucose thus obtained is presently being compared with photosynthetically prepared 11C-D-glucose in PET studies of cerebral metabolism. A preliminary report of the regional cerebral metabolic rate of glucose obtained with the two tracers in a healthy subject with visual stimulation is presented.

Published
1985
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results