Therapeutic Radiopharmaceuticals Labelled with New Emerging Radionuclides (67Cu, 186Re, 47Sc)
Closed for Proposals
Project Type
Coordinated Research ProjectProject Code
F22053
CRP
2073
Approved Date
3 September 2015Project Status
ClosedStart Date
18 March 2016Expected End Date
17 March 2020Completed Date
5 August 2020Description
This Coordinated Research Project (CRP) will identify important technical issues related to the production and quality control of emerging new radionuclides for use in the development of therapeutic radiopharmaceuticals. 67Cu, 186Re and 47Sc radionuclides have been selected based on their theranostic potential and their dual production routes through reactors and cyclotrons, target availability, and high specific activity production. Based on potential demand of member states a collaborated research is needed for the establishment of standardized production, quality control and other important issues including preparation of technical protocols and guidelines for ultimate radiopharmaceutical development. The CRP is focused on production methods of the 67Cu, 186Re and 47Sc radioisotopes as Theranostic Radionuclides for possible radiopharmaceutical development as well as research purposes.The objectives for this CRP are to:Formulate guidelines to enhance and strengthen the expertise and capability of Member States in deploying emerging 67Cu, 186Re and 47Sc therapeutic radioisotopes with “Theranostic” properties from research reactors and accelerators for medical applications in order to meet MS needs as well as to assimilate new developments and research initiatives.
Objectives
Formulate guidelines to enhance and strengthen the expertise and capability of Member States in deploying emerging 67Cu, 186Re and 47Sc therapeutic radioisotopes with “Theranostic” properties from research reactors and accelerators for medical applications in order to meet national needs as well as to assimilate new developments.
Specific Objectives
Development of preliminary procedures for preparation of potential Radiopharmaceuticals of interest based on the mentioned radioisotopes and preclinical studies.
Production of 67Cu, 186Re and 47Sc radionuclides using research reactors and accelerators for some participants for research and clinical use.
Development of target recovery procedures for the future productions based on the production methods under unified bench-marking to optimize the production expenses;
Development of quality control procedures for the produced radionuclides based on the production methods under unified bench-marking at the CRP group.
Development of targetry procedures for the radionuclide production based on the production methods under unified bench-marking at the CRP group.
Impact
The participants have enabled highly collaborative efforts which leverages the expertise offered by each of the participants. For example: CRP participants from Australia, Egypt, India, Iran and Poland have significant experience with isotope production with reactors, CRP participants from France, Hungary, Iran, Italy and Malaysia have expertise related to cross section measurements and/or theoretical modelling, CRP participants from Korea, Iran, Poland, Syria and USA have expertise related to target preparation (including recycling), CRP participants from Egypt, France, Japan, India, Iran, Italy, Syria, Poland and USA have expertise related to isotope purification techniques and CRP participants from Egypt, India, Poland, Saudi Arabia and USA have experience in peptide chemistry and radiolabelling.
The technical impacts of CRP are:
? Explore efficient production methods of 67Cu, 186Re and 47Sc radionuclides using research reactors and in accelerators for research and clinical use.
? Development of targetry procedures for the radionuclide production
? Development of quality control procedures based on the production methods
? Development of target recovery procedures based on the production methods
? Development of preliminary procedures for preparation of potential radiopharmaceuticals based on the radioisotopes of interest and preclinical studies.
Relevance
The CRP was involved the development of standardized production, quality control and recovery procedures for new emerging beta emitter “Theranostic” radionuclides (67Cu, 186Re and 47Sc) for ultimate use in radiopharmaceutical development.
CRP Publications
Poland
Conference Presentations
2018
D. Pawlak, W. Wojdowska, I. Cieszykowska, M. Zoltowska, Z. Tyminski, J.L. Parus, R. Mikolajczak. Production of 47Sc in Maria Reactor in Polatom. Annual Congress of the European Association of Nuclear Medicine, EANM 2018. 13-17 October 2018. Dusseldorf, Germany. Abstrakt published in Eur J Nucl Med Mol Imaging (2018)45 (Suppl.1)
Poland
Conference Presentations
2017
A. Bilewicz, R.Misiak, R.Walczak, M.Pruszynski, Cyclotron production of scandium radionuclides (43Sc, 44Sc and 47Sc) for theranostic application. Portuguese National Nuclear Medicine Congress, Lisbon, November 25-26, 2017
Italy
research paper
2020
Gaia Pupillo et al., New results on the natV(p,x)43Sc cross section: Analysis of the discrepancy with previous data, Nuclear Instruments and Methods in Physics Research Section B Beam Interactions with Materials and Atoms 464:32-35 · February 2020
Malaysia/Japan
Research paper
2018
Mayeen Uddin Khandaker, Kotaro Nagatsu, Honoka Obata, Katsuyuki Minegishi, Ming-Rong Zhang.Excitation functions of helion-induced nuclear reactions on natural titanium up to 55 MeV. Nucl. Inst. and Methods in Physics Research B 445 (2019) 69–76.
India
research paper
2017
Rubel Chakravarty et al. An electroamalgamation approach to separate 47Sc from neutron-activated 46Ca target for use in cancer theranostics. Journal Separation Science and Technology , Volume 52, 2017 - Issue 14
Japan
Conference Presentations
2017
Tomoyuki Ohya, Hisashi Suzuki, Masami Fukada, Kotaro Nagatsu, Katsuyuki Minegishi, Masayuki Hanyu, Ming-Rong Zhang. Co-precipitation method to separate 67Cu from a large amount of Zn target. ISRS (2017) P377
Iran
conference presentation
2018
N. Zandi, H. Afarideh, M. R. Aboudzadeeh, S. Rajabifar; “New design of neutron flux trap in Tehran Research Reactor for radionuclide production with fast neutron energy threshold by enhancing the fast neutron flux using MCNPX code”; 24th Iranian Nuclear conference, 21-21 Feb. 2018, Isfahan, Iran.
India
research paper
2019
Chakravarty R, Chakraborty S, Jadhav S, Jagadeesan KC, Thakare SV, Dash A., A facile method for electrochemical separation of 181-186Re from proton irradiated natural tungsten oxide target. Appl Radiat Isot. 2019 Dec;154:108885. doi: 10.1016/j.apradiso.2019.108885. Epub 2019 Sep 4.
Poland
Research paper
2017
Misiak, R. Walczak, R.; Was, B. A.Bilewicz, Sc-47 production development by cyclotron irradiation of Ca-48, J.Radioanal.Nucl.Chem. 313 (2017) 429-434
Poland
Proceedings
2017
I. Cieszykowska, D. Pawlak, W. Wojdowska, M. Zoltowska, T. Janiak, J.L. Parus, R. Mikolajczak. 47Sc and 67Cu as novel radioisotopes for radiopharmaceuticals. NUTECH-2017 Conference on Development and Application of Nuclear Technologies, 10-13 September 2017, Krakow, Poland, P118
Poland
Conference Presentations
2019
Walczak, R.; Sitarz, M.; Misiak, R.; Pruszynski, M.; Majkowska-Pilip, A.; Jastrzebski, J.; Haddad, F.; Bilewicz, A. Cyklotronowa produkcja 47Ca dla generatora 47Ca/47Sc. ChemSession’19, Warsaw, Poland (07.06.2019) – POSTER.
Japan
Research paper
2017
Zhao-Hui Jin, Takako Furukawa; Tomoyuki Ohya, Mélissa Degardin, Aya Sugyo, Atsushi B. Tsuji, Yasuhisa Fujibayashi, Ming-Rong Zhang, Tatsuya Higashi, Didier Boturyn, Pascal Dumy, Tsuneo Saga. 67Cu-Radiolabeling of a multimeric RGD peptide for V?3 integrin">aV?3 integrin-targeted radionuclide therapy – stability, therapeutic efficacy, and safety studies in mice. Nucl. Med. Commun. 38 (2017) 347–355
Italy
research paper
2019
Gaia Pupillo,Thomas Sounalet, Nathalie Michel, Liliana Mou, Juan Esposito, New production cross sections for the theranostic radionuclide 67Cu,Nuclear Inst, and Methods in Physics Research B 415 (2018) 41–47
Iran
research paper
2019
A. Jafari, M.R. Aboudzadeh, H. Azizakram, M. Sadeghi, B. Alirezapour, A. Rajabifar, K. Yousefi; “Investigations of proton and deuteron induced nuclear reactions on natural and enriched Titanium, Calcium and Vanadium targets, with special reference to the production of 47Sc” ; Appl. Radiat, Isot. , 152 (2019) 145-155.
Poland
Proceedings
2018
I.Cieszykowska, D. Pawlak, W. Wojdowska, T. Janiak, M. Zoltowska, T. Barcikowski, J.L. Parus, R. Mikolajczak. Production of medical Sc radioisotopes: 44Sc and 47Sc. 17-th Workshop on Targetry and Target Chemistry. 27-31 August 2018, Coimbra, Portugal.
Egypt
research paper
2019
Gizawy MA, Aydia MI, Abdel Monem IM, Shamsel-Din HA, Siyam T.Radiochemical separation of reactor produced Sc-47 from natural calcium target using Poly(acrylamide-acrylic acid)/multi-walled carbon nanotubes composite. Appl Radiat Isot. 2019 Aug;150:87-94. doi: 10.1016/j.apradiso.2019.05.022. Epub 2019 May 17.
Poland
Proceedings
2018
M. Zoltowska, W. Wojdowska, D. Pawlak, I. Cieszykowska, T. Janiak, T. Barcikowski, J.L. Parus, P. Garnuszek, R. Mikolajczak. Production of medical Sc radioisotopes: 44Sc and 47Sc. Radiopharmaceutical developments CERAD/NOMATEN. Young investigators. Symposium. 16 May 2018. Otwock-Swierk, Poland
Poland
Conference Presentations
2019
R. Walczak, R. Misiak, M. Pruszynski, A. Majkowska-Pilip, M. Sitarz, J.Jastrzebski, A. Bilewicz, Cyclotron production of 47Ca for 47Ca/47Sc generator. International Symposium of Radiopharmaceutical Sciences (ISRS 2019), Beijing, China, 26-31.05.2019. oral presentation
Italy
research paper
2020
Gaia Pupillo et al. Production of 67Cu by enriched 70Zn targets: first measurements of formation cross sections of 67Cu, 64Cu, 67Ga, 66Ga, 69mZn and 65Zn in interactions of 70Zn with protons above 45 MeV, Radiochimica Acta · February 2020
Poland
PhD Thesis
2016-2019
Rafal Walczak, PhD Thesis “Scandium radionuclides for theragnostic radiopharmaceuticals” Thesis defended in Institute of Nuclear Chemistry and Technology, 20.11. 2019.
Japan
Research paper
2018
Tomoyuki Ohya, Kotaro Nagatsu, Hisashi Suzuki, Masami Fukada, Katsuyuki Minegishi, Masayuki Hanyu, Ming-Rong Zhang. Small-scale production of 67Cu for a preclinical study via the 64Ni(a,p)67Cu channel. Nucl. Med. Biol. 59 (2018) 56 – 60
Iran
research paper
2017
S.F. Hosseini, M. Sadeghi, M. R. Aboudzadeh; “Theoretical assessment and targeted modeling of TiO2 in reactor towards the scandium radioisotopes estimation”; Appl. Radiat, Isot., 127 (2017) 116-121.
Poland
PhD Thesis
2019
Mateusz Sitarz, PhD Thesis “Research on production of new medical radioisotopes with cyclotron” Thesis defended in Dept. of Physics, Warsaw University, 23.09. 2019.
Japan
Research paper
2016
Katsuyuki Minegishi, Kotaro Nagatsu, Masami Fukada, Hisashi Suzuki, Tomoyuki Ohya, Ming-Rong Zhang. Production of scandium-43 and -47 from a powdery calcium oxide target via the nat/44Ca(a,x)-channel. Appl. Radiat. Isot. 116 (2016) 8 – 12
Poland
Proceedings
2018
D. Pawlak, W. Wojdowska, I. Cieszykowska, M. Zoltowska, Z. Tyminski, J.L. Parus, R. Mikolajczak. Production of 47Sc in nuclear reactor. XVI Congress of Polish Society of Nuclear Medicine 23-26 May 2018, Szczecin, Poland.
Italy
research paper
2019
Gaia Pupillo et al. Cyclotron production of 67Cu: A new measurement of the 68Zn(p,2p)67Cu, 68Zn(p,2n)67Ga and 68Zn(p,3n)66Ga nuclear cross sections,
Iran
research paper
2017
S.F. Hosseini, M.R. Aboudzadeh, M. Sadeghi, A. Ahmadi , M. Rostampour; “Assessment and estimation of 67Cu production yield via deuteron induced reactions on natZn and 70Zn” ; Appl. Radiat, Isot. , 127 (2017) 137-141.
Iran
Research paper
2015
Esmail Mollarazi, Amir R. Jalilian, Fariba Johari-daha, Fatemeh Atyabi, Development of 153Sm-folatepolyethyleneimine-conjugated chitosannanoparticles for targeted therapy, J. Label Compd. Radiopharm 2015, 58 327–335 Copyright ? 2015 John Wiley & Sons, Ltd
Italy
research paper
2019
Gaia Pupillo et al., Preliminary results of the PASTA project, Il Nuovo Cimento C 42:139 · December 2019 with 37 Reads
Poland
Conference Presentations
2019
Walczak, R.; Sitarz, M.; Misiak, R.; Pruszynski, M.; Majkowska-Pilip, A.; Jastrzebski, J.; Haddad, F.; Bilewicz, A. Cyclotron production of 47Ca for 47Ca/47Sc generator. International Symposium on Trends in Radiopharmaceuticals (ISTR-2019), Vienna, Austria (28.10-01.11.2019) – oral presentation.
Poland
Research paper
2019
R. Walczak, W.Gaweda, J. Dudek, J. Choinski, A.Bilewicz, Influence of metal ions on the 44Sc-labeling of DOTATATE. J. Radioanal.Nucl.Chem. 322 (2019) 249-254
Poland
Research paper
2018
M.Sitarz, K.Szkliniarz, J.Jastrzebski, J.Choinski, A.Guertine, F.Haddad, A.Jakubowski, K.Kapinos, M.Kisielinski, A.Majkowska, E.Nigrone, M.Rostampour, A.Stolarz, A.Trzcinska, R.Walczak, J.Wojtkowska, W.Zipper, A.Bilewicz, Production of Sc medical radioisotopes with proton and deuteron beams. Appl. Radiat. Isot. 142 (2018) 104–112.
Malaysia
research paper
2018
Ali SKI, Khandaker MU, Kassim HA. Evaluation of production cross-sections for 186Re theranostic radionuclide via charged-particle induced reactions on Tungsten. Appl Radiat Isot. 2018 May;135:239-250. doi: 10.1016/j.apradiso.2018.01.035. Epub 2018 Jan 31.
Poland
Patent
2017
D. Pawlak, W. Wojdowska, J.L. Parus, R. Mikolajczak, Patent application P.421758 (2017) Method of separation of microamounts of scandium from macroamounts of calcium.
Poland
Conference Presentations
2017
M. Pruszynski, R. Walczak, A. Bilewicz. Scandium radionuclides in nuclear medicine application. 2nd Jagiellonian Symposium on Fundamental and Applied Subatomic Physics; 04-09.06.2017, Cracow, Poland
Poland
Proceedings
2018
R. Mikolajczak, W. Wojdowska, D. Pawlak, I. Cieszykowska, M. Zoltowska, J.L. Parus. Prospects for Sc-47c production in nuclear reactor. The Third International Symposiumon Technetium and other Radiometals in Chemistry and Medicine, TERACHEM 2018, 26-29 September 2018, Bressanone, Italy.
Poland
Conference Presentations
2019
Walczak, R.; Sitarz, M.; Misiak, R.; Pruszynski, M.; Majkowska-Pilip, A.; Jastrzebski, J.; Haddad, F.; Bilewicz, A. Cyclotron production of 47Ca for 47Ca/47Sc generator. The 14th CYCLEUR Workshop, Dresden, Germany (09-10.05.2019) – oral presentation.
Poland
Conference Presentations
2018
A. Bilewicz, R.Walczak, M.Pruszynski, Theranostic radionuclides: from production to radiochemistry. VII CONGRESSO NAZIONALE GICR, Università degli Studi di Ferrara 11-12.05.2018, invited lecture.
Poland
Proceedings
2020
D. Pawlak, W. Wojdowska, T. Dziel, U. K?ster, P. Saganowski, M. Sitarz, Z. Tyminski, M. Zoltowska, R. Mikolajczak. Research on radioisotopic impurities and DGA extraction methods for reactor produced 47Sc. 10th International Conference on Isotopes (10ICI), 03-07 February 2020, Kuala Lumpur, Malaysia (abstract accepted).
Italy
research paper
2019
Gaia Pupillo et al. Production of 47Sc with natural vanadium targets: results of the PASTA project, Journal of Radioanalytical and Nuclear Chemistry · October 2019 with 61 Reads
Japan
Research paper
2019
Tomoyuki Ohya, Kotaro Nagatsu, Masayuki Hanyu, Katsuyuki Minegishi, Ming-Rong Zhang. Simple separation of 67Cu from bulk zinc by coprecipitation using hydrogen sulfide gas and silver nitrate. Radiochim. Acta (2019) doi.org/10.1515/ract-2019-3168
Poland
Conference Presentations
2017
R. Walczak, A. Bilewicz, R. Misiak, A. Majkowska, M. Pruszynski, J. Choinski, M. Sitarz, A. Stolarz, J.Jastrzebski, Cyclotron production of theranostic pair 43Sc - 47Sc on calcium targets. 22th International Symposium on Radiopharmaceutical Sciences, ISRS 2017, 14-19 , Drezden, Germany.
Malayisa/Japan/Austria
Proceedings
2020
Cyclotron production of no carrier added 186gRe radionuclide for theranostic applications, Mayeen Uddin Khandaker, Kotaro Nagatsu, Katsuyuki Minegishi, Ming-Rong Zhang, A.R. Jalilian, Radiation Physics and Chemistry
Poland
Proceedings
2019
R. Mikolajczak, D. Pawlak, W. Wojdowska, I. Cieszykowska, M. Zoltowska, J.L. Parus. Scandium-47 separation by extraction chromatography using TBP resin. 23rd International Symposium on Radiopharmaceutical Sciences, ISRS 2019, Beijing, China, 26-31 May 2019. P-402, abstract published in Journal of Labelled Compounds and Radiopharmaceuticals. 2019;62:suppl 1, S571
Egypt
research paper
2020
Gizawy, Mohamed A./ Mohamed, Nader M. A./ Aydia, Mohamed I./ Soliman, Mohamed A./ Shamsel-Din, Hesham A. Feasibility study on production of Sc-47 from neutron irradiated Ca target for cancer theranostics applications. Volume 108, Issue 3 (Mar 2020)
Poland
Conference Presentations
2019
Walczak, R.; Misiak, R.; Pruszynski, M.; Majkowska-Pilip, A.; Sitarz, M.; Jastrzebski, J.; Haddad, F.; Bilewicz, A. Cyclotron production of 47Ca for 47Ca/47Sc generator. The 23rd International Symposium on Radiopharmaceutical Sciences, Beijing, China (26-31.05.2019) – POSTER
Poland
Conference Presentations
2018
R. Walczak, R. Misiak, M. Pruszynski, A. Majkowska-Pilip, M. Sitarz, J. Jastrzebski, A. Bilewicz, Production of 47Sc on 48Ca targets. Technetium and other Radiometals in Chemistry and Medicine (TERACHEM 2018) Bressanone, Italy, poster
Poland
research Paper
2019
D. W. Pawlak, W. Wojdowska, L. J. Parus, I. Cieszykowska, M. Zoltowska, P. Garnuszek, R. Mikolajczak. Comparison of separation methods for 47Ca/47Sc radionuclide generator. Applied Radiation and Isotopes. 2019 Volume 151, September 2019, Pages 140-144 https://doi.org/10.1016/j.apradiso.2019.05.020
Iran
research paper
2018
N. Zandi, H. Afarideh, M. R. Aboudzadeeh, S. Rajabifar; “Study on a new design of Tehran Research Reactor for radionuclide production based on fast neutrons using MCNPX code”; Appl. Radiat, Isot. , 132 (2018) 61-71.
Japan
Conference Presentations
2017
Kotaro Nagatsu, Katsuyuki Minegishi, Hisashi Suzuki, Masami Fukada, Tomoyuki Ohya, Mayeen Uddin Khandaker, Ming-Rong Zhang. A feasibility study on the production of 186Re from 186W powder target. ISRS (2017) P072