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5. Synthesis and preclinical evaluation of [11C]EAI045 as a PET tracer for imaging tumors expressing mutated epidermal growth factor receptor

Author

Högnäsbacka, Antonia A., Poot, Alex J., Plisson, Christophe, Bergare, Jonas, Bonsall, David R., McCluskey, Stuart P., Wells, Lisa A., Kooijman, Esther, Schuit, Robert C., Verlaan, Mariska, Beaino, Wissam, van Dongen, Guus A. M. S., Vugts, Danielle J., Elmore, Charles S., Passchier, Jan, and Windhorst, Albert D.

Published
2024
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16. Synthesis and preclinical evaluation of [11C]EAI045 as a PET tracer for imaging tumors expressing mutated epidermal growth factor receptor.

Author

Högnäsbacka, Antonia A., Poot, Alex J., Plisson, Christophe, Bergare, Jonas, Bonsall, David R., McCluskey, Stuart P., Wells, Lisa A., Kooijman, Esther, Schuit, Robert C., Verlaan, Mariska, Beaino, Wissam, van Dongen, Guus A. M. S., Vugts, Danielle J., Elmore, Charles S., Passchier, Jan, and Windhorst, Albert D.

Subjects
*EPIDERMAL growth factor receptors, *CETUXIMAB, *POSITRON emission tomography, *NON-small-cell lung carcinoma, *RADIOCHEMICAL purification, *PROTEIN-tyrosine kinase inhibitors
Abstract

Background: Mutations in the epidermal growth factor receptor (EGFR) kinase domain are common in non-small cell lung cancer. Conventional tyrosine kinase inhibitors target the mutation site in the ATP binding pocket, thereby inhibiting the receptor's function. However, subsequent treatment resistance mutations in the ATP binding site are common. The EGFR allosteric inhibitor, EAI045, is proposed to have an alternative mechanism of action, disrupting receptor signaling independent of the ATP-binding site. The antibody cetuximab is hypothesized to increase the number of accessible allosteric pockets for EAI045, thus increasing the potency of the inhibitor. This work aimed to gain further knowledge on pharmacokinetics, the EGFR mutation-targeting potential, and the influence of cetuximab on the uptake by radiolabeling EAI045 with carbon-11 and tritium. Results: 2-(5-fluoro-2-hydroxyphenyl)-2-((2-iodobenzyl)amino)-N-(thiazol-2-yl)acetamide and 2-(5-fluoro-2-hydroxyphenyl)-N-(5-iodothiazol-2-yl)-2-(1-oxoisoindolin-2-yl)acetamide were synthesized as precursors for the carbon-11 and tritium labeling of EAI045, respectively. [11C]EAI045 was synthesized using [11C]CO in a palladium-catalyzed ring closure in a 10 ± 1% radiochemical yield (decay corrected to end of [11C]CO2 production), > 97% radiochemical purity and 26 ± 1 GBq/µmol molar activity (determined at end of synthesis) in 51 min. [3H]EAI045 was synthesized by a tritium-halogen exchange in a 0.2% radiochemical yield, 98% radiochemical purity, and 763 kBq/nmol molar activity. The ability of [11C]EAI045 to differentiate between L858R/T790M mutated EGFR expressing H1975 xenografts and wild-type EGFR expressing A549 xenografts was evaluated in female nu/nu mice. The uptake was statistically significantly higher in H1975 xenografts compared to A549 xenografts (0.45 ± 0.07%ID/g vs. 0.31 ± 0.10%ID/g, P = 0.0166). The synergy in inhibition between EAI045 and cetuximab was evaluated in vivo and in vitro. While there was some indication that cetuximab influenced the uptake of [3H]EAI045 in vitro, this could not be confirmed in vivo when tumor-bearing mice were administered cetuximab (0.5 mg), 24 h prior to injection of [11C]EAI045. Conclusions: EAI045 was successfully labeled with tritium and carbon-11, and the in vivo results indicated [11C]EAI045 may be able to distinguish between mutated and non-mutated EGFR in non-small cell lung cancer mouse models. Cetuximab was hypothesized to increase EAI045 uptake; however, no significant effect was observed on the uptake of [11C]EAI045 in vivo or [3H]EAI045 in vitro in H1975 xenografts and cells. [ABSTRACT FROM AUTHOR]

Published
2024
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17. Sentinel lymph node detection in thyroid carcinoma using [68Ga]Ga-tilmanocept PET/CT: a proof-of-concept study.

Author

de Vries, Lisa H., Lodewijk, Lutske, Ververs, Tessa, Poot, Alex J., van Rooij, Rob, Brosens, Lodewijk A. A., de Krijger, Ronald R., Rinkes, Inne H. M. Borel, Vriens, Menno R., and de Keizer, Bart

Subjects
SENTINEL lymph nodes, POSITRON emission tomography, THYROID cancer, LYMPH node cancer, MEDULLARY thyroid carcinoma, PROOF of concept
Abstract

Purpose: Sentinel lymph node (SLN) biopsy is rarely used for thyroid carcinoma staging. This is due to challenges associated with conventional Tc-99m-labeled tracers, often producing a large hotspot at the injection site, potentially hiding nearby SLNs (shine-through effect). The aim of this study was to demonstrate the feasibility and effectiveness of SLN visualization using the new PET tracer [68Ga]Ga-tilmanocept. Methods: Patients with thyroid carcinoma underwent ultrasound-guided peritumoral injection of [68Ga]Ga-tilmanocept and ICG-[99mTc]Tc-nanocolloid. [68Ga]Ga-tilmanocept PET/CT scans were conducted at 15 min and 60 min post-injection to visualize the SLNs. SLN biopsy was performed using ICG-[99mTc]TC-nanocolloid for intraoperative identification. The corresponding lymph node level was resected for reference. Results: Seven differentiated thyroid carcinoma (DTC) and 3 medullary thyroid carcinoma (MTC) patients were included, of which 6 were clinically node-negative. The median number of SLNs detected on [68Ga]Ga-tilmanocept PET/CT and resected was 3 (range 1–4) and 3 (range 1–5), respectively. Eight SLNs were found on PET/CT in the central compartment and 19 in the lateral compartment. The SLN procedure detected (micro)metastases in all patients except one. Seventeen of 27 pathologically assessed SLNs were positive, 8 negative, and 2 did not contain lymph node tissue, which led to upstaging in 5 out of 6 clinically node-negative patients. Conclusions: [68Ga]Ga-tilmanocept PET/CT identified SLNs in all patients, mainly in the lateral neck. The SLNs were successfully surgically detected and resected using ICG-[99mTc]Tc-nanocolloid. This technique has the potential to improve neck staging, enabling more personalized treatment of thyroid cancer according to the lymph node status. Trial registration: 2021–002470-42 (EudraCT). [ABSTRACT FROM AUTHOR]

Published
2024
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18. Synthesis and Preclinical Evaluation of [Methylpiperazine-11C]brigatinib as a PET Tracer Targeting Both Mutated Epidermal Growth Factor Receptor and Anaplastic Lymphoma Kinase

Author

Högnäsbacka, Antonia A., primary, Poot, Alex J., additional, Kooijman, Esther, additional, Schuit, Robert C., additional, Schreurs, Maxime, additional, Verlaan, Mariska, additional, Beaino, Wissam, additional, van Dongen, Guus A. M. S., additional, Vugts, Danielle J., additional, and Windhorst, Albert D., additional

Published
2023
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22. Correction to:[18F]mFBG PET‑CT for detection and localisation of neuroblastoma: a prospective pilot study (European Journal of Nuclear Medicine and Molecular Imaging, (2023), 50, 4, (1146-1157), 10.1007/s00259-022-06063-6)

Author

Samim, Atia, Blom, Thomas, Poot, Alex J., Windhorst, Albert D., Fiocco, Marta, Tolboom, Nelleke, Braat, Arthur J. A. T., Viol, Sebastiaan L. Meyer, van Rooij, Rob, van Noesel, Max M., Lam, Marnix G. E. H., Tytgat, Godelieve A. M., de Keizer, Bart, Radiology and nuclear medicine, Amsterdam Neuroscience - Brain Imaging, and CCA - Imaging and biomarkers

Abstract

The article [ 18F]mFBG PET‑CT for detection and localisation of neuroblastoma: a prospective pilot study, written by Atia Samim, Thomas Blom, Alex J. Poot, Albert D. Windhorst, Marta Fiocco, Nelleke Tolboom, Arthur J. A. T. Braat, Sebastiaan L. Meyer Viol, Rob van Rooij, Max M. van Noesel, Marnix G. E. H. Lam, Godelieve A. M. Tytgat, and Bart de Keizer, was originally published Online First without Open Access. After publication in volume 50, issue 4, page 1146 - 1157 the author decided to opt for Open Choice and to make the article an Open Access publication.

Published
2023

26. Evaluating the Targeting of a Staphylococcus-aureus-Infected Implant with a Radiolabeled Antibody In Vivo

Author

van Dijk, Bruce, primary, Hooning van Duyvenbode, J. Fred F., additional, de Vor, Lisanne, additional, Nurmohamed, F. Ruben H. A., additional, Lam, Marnix G. E. H., additional, Poot, Alex J., additional, Ramakers, Ruud M., additional, Koustoulidou, Sofia, additional, Beekman, Freek J., additional, van Strijp, Jos, additional, Rooijakkers, Suzan H. M., additional, Dadachova, Ekaterina, additional, Vogely, H. Charles, additional, Weinans, Harrie, additional, and van der Wal, Bart C. H., additional

Published
2023
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27. [18F]mFBG PET-CT for detection and localisation of neuroblastoma: a prospective pilot study

Author

Samim, Atia, primary, Blom, Thomas, additional, Poot, Alex J., additional, Windhorst, Albert D., additional, Fiocco, Marta, additional, Tolboom, Nelleke, additional, Braat, Arthur J. A. T., additional, Viol, Sebastiaan L. Meyer, additional, van Rooij, Rob, additional, van Noesel, Max M., additional, Lam, Marnix G. E. H., additional, Tytgat, Godelieve A. M., additional, and de Keizer, Bart, additional

Published
2022
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29. [18F]mFBG PET-CT for detection and localisation of neuroblastoma: a prospective pilot study.

Author

Samim, Atia, Blom, Thomas, Poot, Alex J., Windhorst, Albert D., Fiocco, Marta, Tolboom, Nelleke, Braat, Arthur J. A. T., Viol, Sebastiaan L. Meyer, van Rooij, Rob, van Noesel, Max M., Lam, Marnix G. E. H., Tytgat, Godelieve A. M., and de Keizer, Bart

Subjects
NEUROBLASTOMA, NORADRENALINE, POSITRON emission tomography, SOFT tissue infections, PEDIATRIC oncology
Abstract

Purpose: Meta-[18F]fluorobenzylguanidine ([18F]mFBG) is a positron emission tomography (PET) radiotracer that allows for fast and high-resolution imaging of tumours expressing the norepinephrine transporter. This pilot study investigates the feasibility of [18F]mFBG PET-CT for imaging in neuroblastoma. Methods: In a prospective, single-centre study, we recruited children with neuroblastoma, referred for meta-[123I]iodobenzylguanidine ([123I]mIBG) scanning, consisting of total body planar scintigraphy in combination with single-photon emission computed tomography-CT (SPECT-CT). Within two weeks of [123I]mIBG scanning, total body PET-CTs were performed at 1 h and 2 h after injection of [18F]mFBG (2 MBq/kg). Detected tumour localisations on scan pairs were compared. Soft tissue disease was quantified by number of lesions and skeletal disease by SIOPEN score. Results: Twenty paired [123I]mIBG and [18F]mFBG scans were performed in 14 patients (median age 4.9 years, n = 13 stage 4 disease and n = 1 stage 4S). [18F]mFBG injection was well tolerated and no related adverse events occurred in any of the patients. Mean scan time for [18F]mFBG PET-CT (9.0 min, SD 1.9) was significantly shorter than for [123I]mIBG scanning (84.5 min, SD 10.5), p < 0.01. Most tumour localisations were detected on the 1 h versus 2 h post-injection [18F]mFBG PET-CT. Compared to [123I]mIBG scanning, [18F]mFBG PET-CT detected a higher, equal, and lower number of soft tissue lesions in 40%, 55%, and 5% of scan pairs, respectively, and a higher, equal, and lower SIOPEN score in 55%, 30%, and 15% of scan pairs, respectively. On average, two more soft tissue lesions and a 6-point higher SIOPEN score were detected per patient on [18F]mFBG PET-CT compared to [123I]mIBG scanning. Conclusion: Results of this study demonstrate feasibility of [18F]mFBG PET-CT for neuroblastoma imaging. More neuroblastoma localisations were detected on [18F]mFBG PET-CT compared to [123I]mIBG scanning. [18F]mFBG PET-CT shows promise for future staging and response assessment in neuroblastoma. Trial registration: Dutch Trial Register NL8152. [ABSTRACT FROM AUTHOR]

Published
2023
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30. 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
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32. Hyperpolarized [5- 13 C,4,4- 2 H 2 ,5- 15 N]-L-glutamine provides a means of annotating in vivo metabolic utilization of glutamine

Author

Eskandari, Roozbeh, primary, Kim, Nathaniel, additional, Mamakhanyan, Arsen, additional, Saoi, Michelle, additional, Zhang, Guannan, additional, Berishaj, Marjan, additional, Granlund, Kristin L., additional, Poot, Alex J., additional, Cross, Justin, additional, Thompson, Craig B., additional, and Keshari, Kayvan R., additional

Published
2022
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34. [18F]mFBG PET/CT imaging outperforms MRI and [68 Ga]Ga-DOTA-TOC PET/CT in identifying recurrence pheochromocytoma.

Author

Suurd, Diederik P. D., Poot, Alex J., van Leeuwaarde, Rachel S., Windhorst, Albert D., Vriens, Menno R., and de Keizer, Bart

Subjects
*ADRENALECTOMY, *NEUROENDOCRINE system, *TUMORS, *MAGNETIC resonance imaging, *PHEOCHROMOCYTOMA
Abstract

The article presents a case study of a 27-year-old woman with biochemical evidence of recurrence of disease after bilateral total adrenalectomy. Topics include pheochromocytomas being neuroendocrine tumors with highly variable clinical presentation; and functional imaging being used to confirm suspicious lesions found through CT or MRI after biochemical evidence of a pheochromocytoma.

Published
2023
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35. Additional file 1 of Performance of nanoScan PET/CT and PET/MR for quantitative imaging of 18F and 89Zr as compared with ex vivo biodistribution in tumor-bearing mice

Author

Chomet, Marion, Schreurs, Maxime, Vos, Ricardo, Verlaan, Mariska, Kooijman, Esther J., Poot, Alex J., Boellaard, Ronald, Windhorst, Albert D., van Dongen, Guus AMS, Vugts, Danielle J., Huisman, Marc C., and Beaino, Wissam

Abstract

Additional file 1. Additional information on phantoms experiments, supplementary tables and figures regarding phantom experiments and in vivo studies.

Published
2021
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39. Hyperpolarized [5-13C,4,4-²H2,5-15N]-L-glutamine provides a means of annotating in vivo metabolic utilization of glutamine.

Author

Eskandari, Roozbeh, Kim, Nathaniel, Mamakhanyan, Arsen, Saoi, Michelle, Zhang, Guannan, Berishaj, Marjan, Granlund, Kristin L., Poot, Alex J., Cross, Justin, Thompson, Craig B., and Keshari, Kayvan R.

Subjects
GLUTAMINE, NUCLEAR magnetic resonance, MAGNETIC resonance, PANCREATIC cancer, ENZYME inhibitors
Abstract

Glutamine is consumed by rapidly proliferating cells and can provide the carbon and nitrogen required for growth through various metabolic pathways. However, delineating the metabolic fate of glutamine is challenging to interrogate in vivo. Hyperpolarized magnetic resonance, by providing high transient nuclear magnetic resonance signals, provides an approach to measure fast biochemical processes in vivo. Aminohydrolysis of glutamine at carbon-5 plays an important role in providing nitrogen and carbon for multiple pathways. Here, we provide a synthetic strategy for isotope-enriched forms of glutamine that prolongs glutamine-C5 relaxation times and thereby reveals in vivo reactions involving carbon-5. We investigate multiple enrichment states, finding [5-13C,4,4-²H2,5-15N]-L-glutamine to be optimal for hyperpolarized measurement of glutamine conversion to glutamate in vivo. Leveraging this compound, we explore pancreatic cancer glutamine metabolism in vivo. Taken together, this work provides a means for studying glutamine metabolic flux in vivo and demonstrates on-target effects of metabolic enzyme inhibitors. [ABSTRACT FROM AUTHOR]

Published
2022
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40. The Development of Positron Emission Tomography Tracers for In Vivo Targeting the Kinase Domain of the Epidermal Growth Factor Receptor.

Author

Högnäsbacka, Antonia, Poot, Alex J., Vugts, Danielle J., van Dongen, Guus A. M. S., and Windhorst, Albert D.

Subjects
*POSITRON emission tomography, *PROTEIN-tyrosine kinases, *NON-small-cell lung carcinoma, *SMALL molecules, *EPIDERMAL growth factor receptors
Abstract

Multiple small molecule PET tracers have been developed for the imaging of the epidermal growth factor receptor (EGFR). These tracers target the tyrosine kinase (TK) domain of the receptor and have been used for both quantifying EGFR expression and to differentiate between EGFR mutational statuses. However, the approaches for in vivo evaluation of these tracers are diverse and have resulted in data that are hard to compare. In this review, we analyze the historical development of the in vivo evaluation approaches, starting from the first EGFR TK PET tracer [11C]PD153035 to tracers developed based on TK inhibitors used for the clinical treatment of mutated EGFR expressing non-small cell lung cancer like [11C]erlotinib and [18F]afatinib. The evaluation of each tracer has been compiled to allow for a comparison between studies and ultimately between tracers. The main challenges for each group of tracers are thereafter discussed. Finally, this review addresses the challenges that need to be overcome to be able to efficiently drive EGFR PET imaging forward. [ABSTRACT FROM AUTHOR]

Published
2022
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43. Head-to-head comparison of DFO* and DFO chelators: selection of the best candidate for clinical 89Zr-immuno-PET

Author

Chomet, Marion, primary, Schreurs, Maxime, additional, Bolijn, Maria J., additional, Verlaan, Mariska, additional, Beaino, Wissam, additional, Brown, Kari, additional, Poot, Alex J., additional, Windhorst, Albert D., additional, Gill, Herman, additional, Marik, Jan, additional, Williams, Simon, additional, Cowell, Joseph, additional, Gasser, Gilles, additional, Mindt, Thomas L., additional, van Dongen, Guus A. M. S, additional, and Vugts, Danielle J., additional

Published
2020
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45. Stereocontrolled [11C]Alkylation of N-Terminal Glycine Schiff Bases To Obtain Dipeptides

Author

Filp, Ulrike, Pekošak, Aleksandra, Poot, Alex J., Windhorst, Albert D., Radiology and nuclear medicine, and Amsterdam Neuroscience - Brain Imaging

Abstract

The use of various quaternary ammonium salts as chiral phase-transfer catalysts allowed effective and stereoselective radiochemical [11C]alkylation to obtain functionalized dipeptides. We herein report a broadly applicable procedure for the asymmetric [11C]alkylation of dipeptides to give labeled N-terminal peptides by using different [11C]alkyl halides. Contended stereoselectivities of the reactions were observed by using 11C-labeled alkyl halides, [11C]methyl iodide and [11C]benzyl iodide, and diastereomeric ratios with different specialized catalysts of 95:5 and 90:10 were achieved, respectively. Accordingly, the straightforward synthesis of enantioenriched compounds should play a vital role in peptide-based radiopharmaceutical development and positron emission tomography imaging.

Published
2017

46. Efficient Synthesis of 11C-Acrylesters, 11C-Acrylamides and Their Application in Michael Addition Reactions for PET Tracer Development

Author

Filp, Ulrike, Pees, Anna L., Taddei, Carlotta, Pekošak, Aleksandra, Gee, Antony D., Windhorst, Albert D., Poot, Alex J., Amsterdam Neuroscience - Brain Imaging, and Radiology and nuclear medicine

Abstract

Here we present a new Michael addition reaction utilizing carbon-11 labeled acrylic esters and amides. Subsequently, reactions of these synthons with commercially available Schiff base precursors are performed to produce [11C]glutamate and [11C]glutamine. This methodology is especially useful for the development of positron emission tomography (PET) imaging agents as it offers a new array of potential carbon-11 labeled compounds with this original 11C–C bond forming strategy.

Published
2017

48. Synthesis and Preclinical Evaluation of the First Carbon-11 Labeled PET Tracers Targeting Substance P1–7

Author

Pekošak, Aleksandra, primary, Bulc, Janez Ž., additional, Korat, Špela, additional, Schuit, Robert C., additional, Kooijman, Esther, additional, Vos, Ricardo, additional, Rongen, Marissa, additional, Verlaan, Mariska, additional, Takkenkamp, Kevin, additional, Beaino, Wissam, additional, Poot, Alex J., additional, and Windhorst, Albert D., additional

Published
2018
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49. Stereoselective 11C Labeling of a 'Native' Tetrapeptide by Using Asymmetric Phase-Transfer Catalyzed Alkylation Reactions

Author

Pekošak, Aleksandra, Rotstein, Benjamin H., Collier, Thomas L., Windhorst, Albert D., Vasdev, Neil, Poot, Alex J., Amsterdam Neuroscience - Brain Imaging, and Radiology and nuclear medicine

Abstract

The first 11C-labeled unmodified (“native”) peptide is described by alkylation of a tetrapeptide Schiff base, which was achieved by an automated five-step radiochemical reaction. In a proof-of-concept study, [11C]Phe-d-Trp-Lys-Thr was synthesized. This tetrapeptide is the essential pharmacophore of octreotide, an antagonist of somatostatin receptors. The asymmetric alkylation with chiral phase-transfer catalysts enabled direct labeling of a variety of isolated 11C-peptides in a highly stereoselective manner (94 % de) with acceptable radiochemical yields (9–10 %) and practical specific activities (15–35 GBq µmol–1 or 405–945 mCi µmol–1) at the end of synthesis. This novel methodology provides a powerful new radiosynthetic method to access novel, stereochemically pure carbon-11-labeled native small peptides ready for in vivo studies.

Published
2017

50. Whole body PD-L1 PET in patients with NSCLC and melanoma.

Author

Leung, David K., primary, De Langen, Joop, additional, Raunig, David, additional, Niemeijer, Anna-Larissa N., additional, Smit, Egbert F., additional, Boellaard, Ronald, additional, Vallez-Garcia, David, additional, Dongen, G.a.M.S. van, additional, Windhorst, A.D., additional, Huisman, Marc C., additional, Glaudemans, Andor W. J. M., additional, Hendrikse, N. Harry, additional, Smith, Ralph Adam, additional, Poot, Alex J., additional, Lipovsek, Dasa, additional, Donnelly, David J., additional, Bonacorsi, Samuel J., additional, Velasquez, Linda M., additional, Du, Shuyan, additional, and Hayes, Wendy, additional

Published
2018
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