Journal of Flow Chemistry
Volume/Issue:
Volume 6: Issue 2
Multiparametric labeling optimization and synthesis of 68Ga-labeled compounds applying a continuous-flow microfluidic methodology
Authors:
Gábor Máté University of Debrecen, Nagyerdei krt. 98 H-4032 Debrecen, Hungary

Search for other papers by Gábor Máté in
Current site
Google Scholar
PubMed Close
,
Dezső Szikra University of Debrecen, Nagyerdei krt. 98 H-4032 Debrecen, Hungary

Search for other papers by Dezső Szikra in
Current site
Google Scholar
PubMed Close
,
Jakub Šimeček Technische Universität München, Walther-Meissner Strasse 3, D-85748 Garching, Germany

Search for other papers by Jakub Šimeček in
Current site
Google Scholar
PubMed Close
,
Szandra Szilágyi University of Debrecen, Nagyerdei krt. 98 H-4032 Debrecen, Hungary

Search for other papers by Szandra Szilágyi in
Current site
Google Scholar
PubMed Close
,
György Trencsényi University of Debrecen, Nagyerdei krt. 98 H-4032 Debrecen, Hungary

Search for other papers by György Trencsényi in
Current site
Google Scholar
PubMed Close
,
Hans-Jürgen Wester Technische Universität München, Walther-Meissner Strasse 3, D-85748 Garching, Germany

Search for other papers by Hans-Jürgen Wester in
Current site
Google Scholar
PubMed Close
,
István Kertész University of Debrecen, Nagyerdei krt. 98 H-4032 Debrecen, Hungary

Search for other papers by István Kertész in
Current site
Google Scholar
PubMed Close
, and
László Galuska University of Debrecen, Nagyerdei krt. 98 H-4032 Debrecen, Hungary

Search for other papers by László Galuska in
Current site
Google Scholar
PubMed Close
Pages:
86–93
Online Publication Date:
Jun 2016
Publication Date:
01 Jun 2016
Article Category:
Research Article
DOI:
https://doi.org/10.1556/1846.2016.00004
Restricted access

The synthesis and functional evaluation of a wide variety of radiolabeled chelator–biomolecule conjugates with high specific activity and radiochemical purity are crucial to development of personalized nuclear medicine. An excellent platform technology for achieving this objective involves use of generator-produced positron emission tomography (PET)-radionuclide 68Ga. Currently, applied manual methodology for optimization and development for new labeling techniques offers only slow screening with relatively high precursor consumption. A capillary-based microfluidic synthesis module with online high-performance liquid chromatography (HPLC) was constructed for the optimization of reaction parameters of 68Ga-PET tracers. This approach enables performance of 68Ga-labeling reactions in 10 μL volumes, followed by sample analysis. The high-throughput capacity of the system allows very rapid optimization. The optimal pH and ligand concentration from the experiments were utilized directly to the production of 68Ga-NODAGA-(RGD)2 and 68Ga-NOPO-RGD. Applying optimal parameters to production of these aforementioned radiopharmaceuticals allowed their synthesis with high radiochemical purity (over 95%) and with surprisingly negligible retention of residual activity in the system.

  • 1.

    Elizarov, A. M.; van Dam, R. M.; Shin ,Y. S.; Kolb, H. C.; Padgett, H. C.; Stout, D.; Shu, J.; Huang, J.; Daridon, A.; Heath, J. R. J. Nucl. Med. 2010, 51, 282–287.

    • Search Google Scholar
    • Export Citation
  • 2.

    Boschi, S.; Malizia, C.; Lodi, F. Recent Results Cancer Res. 2013, 194, 17–31.

  • 3.

    Boschi, S.; Lodi, F.; Malizia, C.; Cicoria, G.; Marengo M. Appl. Radiat. Isot. 2013, 76, 38–45

  • 4.

    Fuchtner, F.; Preusche, S.; Mading, P.; Zessin, J.; Steinbach, J. Nuklearmedizin. Nucl. Med. 2008, 47, 116–119

  • 5.

    Lee, C. C.; Sui, G.; Elizarov, A.; Shu, C. J.; Shin, Y. S.; Dooley, A. N.; Huang, J.; Daridon, A.; Wyatt, P.; Stout, D.; Kolb, H. C.; Witte, O. N.; Satyamurthy, N.; Heath, J. R.; Phelps, M. E.; Quake, S. R., Tseng, H. R. Science 2005, 310, 1793–1796.

    • Search Google Scholar
    • Export Citation
  • 6.

    Roberge, D. M.; Ducry, L.; Bieler, N.; Cretton, P.; Zimmerman, B. Chem. Eng. Technol. 2005, 28, 318–323.

  • 7.

    Lu, S. Y.; Pike, V. W. The Driving Force in Molecular Imaging; Schubiger, P. A.; Lehmann, L.; Friebe, M., Eds.; Springer-Verlag: Heidelberg, 2006; pp. 271–289.

    • Search Google Scholar
    • Export Citation
  • 8.

    Watts, P.; Haswell, S. J. Chem. Eng. Technol. 2005, 28, 290–301.

  • 9.

    Kang, L.; Chung, B. G.; Langer, R.; Khademhosseini, A. Drug Discov. Today 2008, 13, 1–13.

  • 10.

    Huebner, A.; Sharma, S.; Srisa-Art, M.; Hollfelder, F.; Edel, J. B.; de Mello, A. J. Lab Chip 2008, 8, 1244–1254.

  • 11.

    Miller, P. W. J. Chem. Technol. Biotechnol. 2009, 84, 309–315.

  • 12.

    Fortt, R.; Gee, A. Future Med. Chem. 2013, 5, 241–244.

  • 13.

    Pascali, G.; Watts, P.; Salvadori, P. A. Nucl. Med. Biol. 2013, 40, 776–787, 8–323.

  • 14.

    Elizarov, A. M. Lab Chip 2009, 9, 1326–1333.

  • 15.

    Keng, P. Y.; Esterby, M.; van Dam, R. M. In Positron Emission Tomography — Current Clinical and Research Aspects; Hsieh, C.-H. Ed.; InTech, DOI: 10.5772/31390. Available from: http://www.intechopen.com/books/positronemission- tomography-current-clinical-and-research-aspects/emerging-technologiesfor- decentralized-production-of-pet-tracers.

    • Search Google Scholar
    • Export Citation
  • 16.

    Gillies, J. M.; Prenant, C.; Chimon, G. N.; Smethurst, G. J.; Dekker, B. A.; Zweit, J. Appl. Radiat. Isot. 2006, 64, 333–336.

  • 17.

    Audrain, H. Angew. Chem., Int. Ed. Engl. 2007, 46, 1772–1775.

  • 18.

    Lebedev, A.; Miraghaie, R.; Kotta, K.; Ball, C. E.; Zhang, J.; Buchsbaum, M. S.; Kolb, H. C.; Elizarov, A. Lab Chip 2013, 13, 136–145.

    • Search Google Scholar
    • Export Citation
  • 19.

    Briard, E.; Zoghbi, S. S.; Siméon, F. G.; Imaizumi, M.; Gourley, J. P.; Shetty, H. U.; Lu, S.; Fujita, M.; Innis, R. B.; Pike, V. W. J. Med. Chem. 2009, 52, 688–699.

    • Search Google Scholar
    • Export Citation
  • 20.

    Wester, H. J.; Schoultz, B. W.; Hultsch, C.; Henriksen, G. Eur. J. Nucl. Med. Mol. Imaging 2009, 36, 653–658.

  • 21.

    Pascali, G.; Mazzone, G.; Saccomanni, G.; Manera, C.; Salvadori, P. A. Nucl. Med. Biol. 2010, 37, 547–555.

  • 22.

    Liu, K.; Lepin, E. J.; Wang, M.W.; Guo, F.; Lin, W. Y.; Chen, Y. C.; Sirk, S. J.; Olma, S.; Phelps, M. E.; Zhao, X. Z.; Tseng, H.R.; Michael vanDam, R.; Wu, A. M.; Shen, C. K. Mol. Imaging 2011, 10, 168–176.

    • Search Google Scholar
    • Export Citation
  • 23.

    Wheeler, T. D.; Zeng, D.; Desai, A. V.; Onal, B.; Reichert, D. E.; Kenis, P. J. Lab Chip 2010, 10, 3387–3396.

  • 24.

    Zeng, D.; Desai, A. V.; Ranganathan, D.; Wheeler, T. D.; Kenis, P. J.; Reichert, D. E. Nucl. Med. Biol. 2013, 40, 42–51.

  • 25.

    Rösch, F. Appl. Radiat. Isot. 2013, 76, 24–30

  • 26.

    Decristoforo, C. Curr. Radiopharm. 2012, 5, 212–220.

  • 27.

    Lee, V. S. Recent Results Cancer Res. 2013, 194, 43–75.

  • 28.

    Velikyan, I. Theranostics 2014, 4, 47–80.

  • 29.

    Morgat, C.; Hindié, E.; Mishra, A. K.; Allard, M.; Fernandez, P. Cancer Biother. Radiopharm. 2013, 28, 85–97.

  • 30.

    Decristoforo, C.; Pickett, R. D.; Verbruggen, A. Eur. J. Nucl. Med. Mol. Imaging 2012, Suppl. 1, S31–S40.

  • 31.

    Máté, G.; Kertész, I.; Enyedi, K. N.; Mezo, G.; Angyal, J.; Vasas, N.; Kis, A.; Szabó, É.; Emri, M.; Bíró, T.; Galuska, L.; Trencsényi, Gy. Eur. J. Pharm. Sci. 2015, 69, 61–71.

    • Search Google Scholar
    • Export Citation
  • 32.

    Šimecek, J.; Hermann, P.; Wester, H. J.; Notni, J. ChemMedChem. 2013, 8, 95–103.

  • 33.

    Notni, J.; Šimecek, J.; Wester, H. J. ChemMedChem. 2014, 9, 1107–1115 (corrigendum: ibid. 2014, 9, 2614).

  • 34.

    Šimecek, J.; Zemek, O.; Hermann, P.; Notni, J.; Wester, H. J. Mol. Pharmaceutics 2014, 11, 3893-3903.

  • 35.

    Šimecek, J.; Notni, J.; Kapp, T. G.; Kessler, H.; Wester, H. J. Mol. Pharmaceutics. 2014, 11, 1687–1695.

  • 36.

    Šimecek, J.; Zemek, O.; Hermann, P.; Wester, H. J.; Notni, J. ChemMed-Chem 2012, 7, 1375–1378.

  • 37.

    Notni, J.; Šimecek, J.; Hermann, P.; Wester, H. J. Chem. Eur. J. 2011, 17, 14718–14722.

  • 38.

    Rensch, C.; Jackson, A.; Lindner, S.; Salvamoser, R.; Samper, V.; Riese, S.; Bartenstein, B.; Wängler, C.; Wängler, B. Molecules 2013, 18, 7930–7956.

    • Search Google Scholar
    • Export Citation
  • 39.

    Baes, C. F.; Mesmer, R. E. The Hydrolysis of Cations, John Wiley & Sons: New York, 1976; pp. 320–322.

  • 40.

    Martins, A. F.; Prata, M. I.; Rodriguese, S. P.; Geraldes, C. F.; Riss, P. J.; Amor-Coarasa, A.; Burchardt, C.; Kroll, C.; Roesch, F. Contrast Media Mol. Imaging 2013, 8, 265–273.

    • Search Google Scholar
    • Export Citation
  • 41.

    Sokolowska, M.; Bal, W. J. Inorg. Biochem. 2005, 99, 1653–1660.

  • 42.

    Szikra, D.; Mate, G.; Nagy, G. J. Nucl. Med. 2015, 56, 75.

  • Collapse
  • Expand
Cover Journal of Flow Chemistry
Journal of Flow Chemistry A Journal of the Flow Chemistry Society
Print ISSN:
2062-249X
Online ISSN:
2063-0212

To see the editorial board, please visit the website of Springer Nature.

Manuscript Submission: HERE

For subscription options, please visit the website of Springer Nature.

Journal of Flow Chemistry
Language English
Size A4
Year of
Foundation		 2011
Volumes
per Year		 1
Issues
per Year		 4
Founder Áramlásos Kémiai Tudományos Társaság
Founder's
Address		 H-1031 Budapest, Hungary Záhony utca 7.
Publisher Akadémiai Kiadó
Springer Nature Switzerland AG
Publisher's
Address		 H-1117 Budapest, Hungary 1516 Budapest, PO Box 245.
CH-6330 Cham, Switzerland Gewerbestrasse 11
Responsible
Publisher		 Chief Executive Officer, Akadémiai Kiadó
ISSN 2062-249X (Print)
ISSN 2063-0212 (Online)

Monthly Content Usage

Abstract Views Full Text Views PDF Downloads
Jun 2023 6 0 0
Jul 2023 21 0 0
Aug 2023 14 0 0
Sep 2023 8 0 0
Oct 2023 7 9 0
Nov 2023 4 2 1
Dec 2023 0 0 0