Final Report Summary - RADIOMI (Innovative Radiochemistry to Advance Molecular Imaging)
The main research objective of the RADIOMI ITN was to provide a coordinated first class training program and innovation in radiochemistry for molecular imaging. A collaborative network of early stage researchers (ESR) and experienced researchers (ER) was established at 8 partner institutions across Europe. In a comprehensive training program, in addition to the national PhD programs of each hosting institutions, young scientists were trained to develop and perform innovative radiolabeling with the short half-life positron emitting isotopes 18F (109.8 mins), 11C (20.4 mins) and 13N (10 mins). New and improved methods were tested in the synthesis of known and new radiotracers (small molecules, peptides, libraries of labeled compounds) notoriously difficult to prepare and/or to access in a pure form, with the required quality and in a reproducible manner. Preclinical evaluations were carried out on selected tracers.
Main goals of the RADIOMI network:
• High quality science
• High quality training
• Joint papers
• Leverage other grant applications
Key achievements:
- 18 fellows appointed (ESR - 15, ER – 3).
- Gender balance target reached (>60% women).
- Training completed – Synthesis, Catalysis, Radiochemistry, Radiopharmaceuticals, Nanotechnology, and Complementary skills.
- RADIOMI International Meetings – 6, Schools – 4, Workshops - 3.
- Secondments completed.
- Awarded - 4 prizes for oral presentations, 6 prizes for posters, 1 fellowship.
- 26 scientific papers published in leading international journals.
List of publications by institution:
UNIVERSITY OF OXFORD, UK (8):
- cic-Specific Hydrofluorination of Alkenylarenes under Palladium Catalysis by an Ionic Pathway. E. Emer, L. Pfeifer, J. M. Brown, V. Gouverneur. Angewandte Chemie International Edition (2014), 53 (16), 4181–4185
- Coordination Diversity in Hydrogen-Bonded Homoleptic Fluoride–Alcohol Complexes Modulates Reactivity. K. M. Engle, L. Pfeifer, G. W. Pidgeon, G. T. Giuffredi, A. L. Thompson, R. S. Paton, J. M. Brown, V. Gouverneur. Chemical science (2015), 6, 5293-5302 (Edge Article)
- [18F]Labeling of Aryl-SCF3, -OCF3 and -OCHF2 with [18F]Fluoride . T. Khotavivattana, S. Verhoog, M. Tredwell, L. Pfeifer, S. Calderwood, K. Wheelhouse, T. L. Collier, V. Gouverneur. Angewandte Chemie International Edition (2015), 54 (34), 9991-9995
- Cross-Coupling of [2-Aryl-1,1,2,2-tetrafluoroethyl]trimethylsilanes with Aryl Halides
M. O'Duill, E. Dubost, L. Pfeifer, V. Gouverneur. Organic Letters (2015), 17 (14), 3466-3469
- Ag-Mediated 18F-Labeling of Aryl-CF3 and Aryl-CHF2 with 18F-Fluoride. S. Verhoog, L. Pfeifer, T. Khotavivattana, S. Calderwood, T. L. Collier, K. Wheelhouse, M. Tredwell, V. Gouverneur. Synlett (2016), 27, 25-28. In celebration of Prof. Steven Ley’s 70th birthday
- Hydrogen-Bonded Homoleptic Fluoride–Diarylurea Complexes: Structure, Reactivity and Coordinating Power. L. Pfeifer, K. M. Engle, G. W. Pidgeon, H. A. Sparkes, A. L. Thompson, J. M. Brown, V. E. Gouverneur. J. Am. Chem. Soc. (2016), 138 (40), 13314-13325
- The Dual Role of Thiourea in the Thiotrifluoromethylation of Alkenes. P. Ricci, T. Khotavivattana, L. Pfeifer, M. Médebielle, J. R. Morphy, V. Gouverneur. Chem. Sci. 2016, DOI: 10.1039/C6SC02790C (In Print)
- Twisting the Ethano-Tröger’s Base: The Bisamide. J. Cvengros, R. Pereira, L. Pfeifer, J. Fournier, V. Gouverneur. Org. Biomol. Chem. (2016), DOI: 10.1039/C6OB02359B (In Print)
KING’S COLLEGE LONDON, UK (2):
- Synthesis of 11C-Labelled Symmetrical Ureas via the Rapid Incorporation of [11C]CO2 into Aliphatic and Aromatic Amines, A. K. Haji Dheere, S. Bongarzone, C. Taddei, R. Yan, A. D. Gee, Synlett, 2015, 26, 2257-2260.
- [11C]CO2 to [11C]CO conversion mediated by [11C]silanes: a novel route for [11C]carbonylation reactions, C. Taddei, S. Bongarzone, A. K. Haji Dheere, A. D. Gee, Chem. Commun., 2015,51, 11795-11797.
TURUN YLIOPISTO, FINLAND (4):
- Organomediated Enantioselective 18F-Fluorination for PET Applications. F. Buckingham, A. K. Kirjavainen, S. Forsback, A. Krzyczmonik, T. Keller, I. M. Newington, M. Glaser, S. K. Luthra, O. Solin, V. Gouverneur. Angewandte Chemie International Edition (2015), 54 (45), 13366-13369
- Oxidative Fluorination of N-Arylsulfonamides. F. Buckingham, S. Calderwood, B. Checa, T. Keller, M. Tredwell, T. L. Collier, I. M. Newington, R. Bhalla, M. Glaser, V. Gouverneur. Journal of Fluorine Chemistry (2015), 180, 33-39
- Ultrafast Click Chemistry with Fluorosydnones. H. Liu, D. Audisio, L. Plougastel, E. Decuypere, D.-A. Buisson, O. Koniev, S. Kolodych, A. Wagner, M. Elhabiri, A. Krzyczmonik, S. Forsback, O. Solin, V. Gouverneur, F. Taran. Angewandte Chemie International Edition (2016), 55 (39), 12073-12077
- Brain energy metabolism and neuroinflammation in ageing APP/PS1-21 mice using longitudinal 18F-FDG and 18F-DPA-714 PET imaging. J. S. Takkinen, F. R. López-Picón, R. Al Majidi, O. Eskola, A. Krzyczmonik, T. Keller, E. Löyttyniemi, O. Solin, J. O. Rinne, M. Haaparanta-Solin. J. Cereb. Blood Flow Metab. (2016), DOI: 10.1177/0271678X16677990 (In Print)
STICHTING VUMC, THE NETHERLANDS (3):
- Improved synthesis and application of [11C]benzyl iodide in positron emission tomography radiotracer production. A. Pekošak, U. Filp, L. Rotteveel, A. J. Poot, A. D. Windhorst. Journal of Labelled Compounds and Radiopharmaceuticals (2015), 58 (8), 342-348
- Enantioselective synthesis of carbon-11 labeled L-alanine using phase transfer catalysis of Schiff bases. U. Filp, A. Pekošak, A. J. Poot, A. D. Windhorst. Tetrahedron (2016), 72 (41), 6551-6557
- A rapid and highly enantioselective C–11C bond formation of L-[11C]phenylalanine via chiral phase-transfer catalysis. A. Pekošak, U. Filp, J. Škrinjar, A. J. Poot, A. D. Windhorst. Org. Biomol. Chem. (2017), Advance Article, DOI: 10.1039/C6OB02633H (In Print)
UNIVERSITE LYON 1 CLAUDE BERNARD, FRANCE (4):
- Acid-Catalyzed Synthesis of α-Trifluoromethylthiolated Carbonyl Compounds. S. Alazet, E. Ismalaj, Q. Glenadel, D. Le Bars, T. Billard. European Journal of Organic Chemistry (2015), 21, 4607-4610
- Direct [11C]Methylation of Amines from [11C]CO2 for the Synthesis of PET Radiotracers. F. Liger, T. Eijsbouts, F. Cadarossanesaib, C. Tourvieille, D.Le Bars, T. Billard. European Journal of Organic Chemistry (2015), 29, 6434-6438
- Direct Electrophilic (Benzenesulfonyl)Difluoromethylthiolation with a Shelf-Stable Reagent. E. Ismalaj, D. Le Bars, T. Billard. Angewandte Chemie International Edition (2016), 55 (15), 4790-4793
- Benzyltrifluoromethyl (or Fluoroalkyl) Selenide: Reagent for Electrophilic Trifluoromethyl (or Fluoroalkyl) Selenolation. Q. Glenadel, E. Ismalaj, T. Billard. J. Org. Chem. (2016), 81 (18), 8268–8275
ASOCIACION CENTRO DE INVESTIGACION COOPERATIVA EN BIOMATERIALES - CIC biomaGUNE (5):
- Synthesis and Evaluation of 13N-Labelled Azo Compounds for β-Amyloid Imaging in Mice. V. Gaja, V. Gómez-Vallejo, M. Puigivila, C. Pérez-Campaña, A. Martin, A. García-Osta, T. Calvo-Fernández, M. Cuadrado-Tejedor, R. Franco, J. Llop. Molecular Imaging and Biology, (2014), 16 (4), 538-549
- Efficient Nitrogen-13 radiochemistry catalyzed by a highly stable immobilized biocatalyst. E. da Silva, V. Gómez-Vallejo, J. Llop, F. López Gallego. Catalysis Science and Technology (2015), 15, 2705-2713
- Synthesis of Radiolabelled Aryl Azides from Diazonium Salts: Experimental and Computational Results Permit to Identify the Preferred Mechanism. S. M. Joshi, A. de Cózar, V. Gómez-Vallejo, J. Koziorowski, J. Llop, F. P. Cossío. Chemical Communications (2015), 51, 8954-8957
- Efficient Enzymatic Preparation of 13N-Labelled Amino Acids: Towards Multipurpose Synthetic Systems. E. S. da Silva; V. Gómez-Vallejo; Z. Baz; J. Llop, F. López-Gallego. Chemistry - A European Journal (2016), 22 (38), 13619-13626
- Synthesis of 13N-labelled polysubstituted triazoles via Huisgen cycloaddition. S. M. Joshi, V. Gómez-Vallejo, V. Salinas, J. Llop. RSC Adv. (2016), 6, 109633-109638.
Main goals of the RADIOMI network:
• High quality science
• High quality training
• Joint papers
• Leverage other grant applications
Key achievements:
- 18 fellows appointed (ESR - 15, ER – 3).
- Gender balance target reached (>60% women).
- Training completed – Synthesis, Catalysis, Radiochemistry, Radiopharmaceuticals, Nanotechnology, and Complementary skills.
- RADIOMI International Meetings – 6, Schools – 4, Workshops - 3.
- Secondments completed.
- Awarded - 4 prizes for oral presentations, 6 prizes for posters, 1 fellowship.
- 26 scientific papers published in leading international journals.
List of publications by institution:
UNIVERSITY OF OXFORD, UK (8):
- cic-Specific Hydrofluorination of Alkenylarenes under Palladium Catalysis by an Ionic Pathway. E. Emer, L. Pfeifer, J. M. Brown, V. Gouverneur. Angewandte Chemie International Edition (2014), 53 (16), 4181–4185
- Coordination Diversity in Hydrogen-Bonded Homoleptic Fluoride–Alcohol Complexes Modulates Reactivity. K. M. Engle, L. Pfeifer, G. W. Pidgeon, G. T. Giuffredi, A. L. Thompson, R. S. Paton, J. M. Brown, V. Gouverneur. Chemical science (2015), 6, 5293-5302 (Edge Article)
- [18F]Labeling of Aryl-SCF3, -OCF3 and -OCHF2 with [18F]Fluoride . T. Khotavivattana, S. Verhoog, M. Tredwell, L. Pfeifer, S. Calderwood, K. Wheelhouse, T. L. Collier, V. Gouverneur. Angewandte Chemie International Edition (2015), 54 (34), 9991-9995
- Cross-Coupling of [2-Aryl-1,1,2,2-tetrafluoroethyl]trimethylsilanes with Aryl Halides
M. O'Duill, E. Dubost, L. Pfeifer, V. Gouverneur. Organic Letters (2015), 17 (14), 3466-3469
- Ag-Mediated 18F-Labeling of Aryl-CF3 and Aryl-CHF2 with 18F-Fluoride. S. Verhoog, L. Pfeifer, T. Khotavivattana, S. Calderwood, T. L. Collier, K. Wheelhouse, M. Tredwell, V. Gouverneur. Synlett (2016), 27, 25-28. In celebration of Prof. Steven Ley’s 70th birthday
- Hydrogen-Bonded Homoleptic Fluoride–Diarylurea Complexes: Structure, Reactivity and Coordinating Power. L. Pfeifer, K. M. Engle, G. W. Pidgeon, H. A. Sparkes, A. L. Thompson, J. M. Brown, V. E. Gouverneur. J. Am. Chem. Soc. (2016), 138 (40), 13314-13325
- The Dual Role of Thiourea in the Thiotrifluoromethylation of Alkenes. P. Ricci, T. Khotavivattana, L. Pfeifer, M. Médebielle, J. R. Morphy, V. Gouverneur. Chem. Sci. 2016, DOI: 10.1039/C6SC02790C (In Print)
- Twisting the Ethano-Tröger’s Base: The Bisamide. J. Cvengros, R. Pereira, L. Pfeifer, J. Fournier, V. Gouverneur. Org. Biomol. Chem. (2016), DOI: 10.1039/C6OB02359B (In Print)
KING’S COLLEGE LONDON, UK (2):
- Synthesis of 11C-Labelled Symmetrical Ureas via the Rapid Incorporation of [11C]CO2 into Aliphatic and Aromatic Amines, A. K. Haji Dheere, S. Bongarzone, C. Taddei, R. Yan, A. D. Gee, Synlett, 2015, 26, 2257-2260.
- [11C]CO2 to [11C]CO conversion mediated by [11C]silanes: a novel route for [11C]carbonylation reactions, C. Taddei, S. Bongarzone, A. K. Haji Dheere, A. D. Gee, Chem. Commun., 2015,51, 11795-11797.
TURUN YLIOPISTO, FINLAND (4):
- Organomediated Enantioselective 18F-Fluorination for PET Applications. F. Buckingham, A. K. Kirjavainen, S. Forsback, A. Krzyczmonik, T. Keller, I. M. Newington, M. Glaser, S. K. Luthra, O. Solin, V. Gouverneur. Angewandte Chemie International Edition (2015), 54 (45), 13366-13369
- Oxidative Fluorination of N-Arylsulfonamides. F. Buckingham, S. Calderwood, B. Checa, T. Keller, M. Tredwell, T. L. Collier, I. M. Newington, R. Bhalla, M. Glaser, V. Gouverneur. Journal of Fluorine Chemistry (2015), 180, 33-39
- Ultrafast Click Chemistry with Fluorosydnones. H. Liu, D. Audisio, L. Plougastel, E. Decuypere, D.-A. Buisson, O. Koniev, S. Kolodych, A. Wagner, M. Elhabiri, A. Krzyczmonik, S. Forsback, O. Solin, V. Gouverneur, F. Taran. Angewandte Chemie International Edition (2016), 55 (39), 12073-12077
- Brain energy metabolism and neuroinflammation in ageing APP/PS1-21 mice using longitudinal 18F-FDG and 18F-DPA-714 PET imaging. J. S. Takkinen, F. R. López-Picón, R. Al Majidi, O. Eskola, A. Krzyczmonik, T. Keller, E. Löyttyniemi, O. Solin, J. O. Rinne, M. Haaparanta-Solin. J. Cereb. Blood Flow Metab. (2016), DOI: 10.1177/0271678X16677990 (In Print)
STICHTING VUMC, THE NETHERLANDS (3):
- Improved synthesis and application of [11C]benzyl iodide in positron emission tomography radiotracer production. A. Pekošak, U. Filp, L. Rotteveel, A. J. Poot, A. D. Windhorst. Journal of Labelled Compounds and Radiopharmaceuticals (2015), 58 (8), 342-348
- Enantioselective synthesis of carbon-11 labeled L-alanine using phase transfer catalysis of Schiff bases. U. Filp, A. Pekošak, A. J. Poot, A. D. Windhorst. Tetrahedron (2016), 72 (41), 6551-6557
- A rapid and highly enantioselective C–11C bond formation of L-[11C]phenylalanine via chiral phase-transfer catalysis. A. Pekošak, U. Filp, J. Škrinjar, A. J. Poot, A. D. Windhorst. Org. Biomol. Chem. (2017), Advance Article, DOI: 10.1039/C6OB02633H (In Print)
UNIVERSITE LYON 1 CLAUDE BERNARD, FRANCE (4):
- Acid-Catalyzed Synthesis of α-Trifluoromethylthiolated Carbonyl Compounds. S. Alazet, E. Ismalaj, Q. Glenadel, D. Le Bars, T. Billard. European Journal of Organic Chemistry (2015), 21, 4607-4610
- Direct [11C]Methylation of Amines from [11C]CO2 for the Synthesis of PET Radiotracers. F. Liger, T. Eijsbouts, F. Cadarossanesaib, C. Tourvieille, D.Le Bars, T. Billard. European Journal of Organic Chemistry (2015), 29, 6434-6438
- Direct Electrophilic (Benzenesulfonyl)Difluoromethylthiolation with a Shelf-Stable Reagent. E. Ismalaj, D. Le Bars, T. Billard. Angewandte Chemie International Edition (2016), 55 (15), 4790-4793
- Benzyltrifluoromethyl (or Fluoroalkyl) Selenide: Reagent for Electrophilic Trifluoromethyl (or Fluoroalkyl) Selenolation. Q. Glenadel, E. Ismalaj, T. Billard. J. Org. Chem. (2016), 81 (18), 8268–8275
ASOCIACION CENTRO DE INVESTIGACION COOPERATIVA EN BIOMATERIALES - CIC biomaGUNE (5):
- Synthesis and Evaluation of 13N-Labelled Azo Compounds for β-Amyloid Imaging in Mice. V. Gaja, V. Gómez-Vallejo, M. Puigivila, C. Pérez-Campaña, A. Martin, A. García-Osta, T. Calvo-Fernández, M. Cuadrado-Tejedor, R. Franco, J. Llop. Molecular Imaging and Biology, (2014), 16 (4), 538-549
- Efficient Nitrogen-13 radiochemistry catalyzed by a highly stable immobilized biocatalyst. E. da Silva, V. Gómez-Vallejo, J. Llop, F. López Gallego. Catalysis Science and Technology (2015), 15, 2705-2713
- Synthesis of Radiolabelled Aryl Azides from Diazonium Salts: Experimental and Computational Results Permit to Identify the Preferred Mechanism. S. M. Joshi, A. de Cózar, V. Gómez-Vallejo, J. Koziorowski, J. Llop, F. P. Cossío. Chemical Communications (2015), 51, 8954-8957
- Efficient Enzymatic Preparation of 13N-Labelled Amino Acids: Towards Multipurpose Synthetic Systems. E. S. da Silva; V. Gómez-Vallejo; Z. Baz; J. Llop, F. López-Gallego. Chemistry - A European Journal (2016), 22 (38), 13619-13626
- Synthesis of 13N-labelled polysubstituted triazoles via Huisgen cycloaddition. S. M. Joshi, V. Gómez-Vallejo, V. Salinas, J. Llop. RSC Adv. (2016), 6, 109633-109638.