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Nuclear medicine has proven to be a much needed medical specialty in order to diagnose and treat several diseases, among them, cardiovascular diseases and cancer, the first and the second causes of mortality worldwide, respectively [1]. Several international agencies recommend to study of new routes and new facilities for producing radioisotopes with application to nuclear medicine as a complementary option to the conventional ones based on nuclear reactors or dedicated cyclotrons [2,3,4]. This has been specially pushed in the last years with the development and the availability of high-intensity accelerators and new installations because they allow the production of emergent or new radioisotopes. In addition, these new installations can provide quantities of various radioisotopes at regional level. CERN’s MEDICIS ISOLDE facility is an excellent example [5].
177Lu is a versatile radioisotope used for therapy and diagnosis (theranostics) of cancer with good success in gastroenteropancreatic neuroendocrine tumours [6]. Currently, the use of 177Lu is under study for several other tumours with good results [7]. 177Lu is produced in a few nuclear reactors mainly by the neutron capture on 176Lu (direct route). However, it could be produced at high-intensity accelerator-based neutron facilities as IFMIF-DONES by means of the route 176Yb(n,γ) (indirect route) [8]. In fact, the produced 177Yb beta-decays to the 177Lu with a half-life of 1.9 h. Although the cross-section of the direct route is higher, several advantages in the indirect route have been pointed out:
i) The specific activity is four times higher. About 100% of the theoretical specific activity can be achieved [9,10].
ii) The contaminants that remain in the final quantity of the material are much lower.
iii) The undesirable 177mLu (t1/2≈160 d) is produced in the direct route, 0.05%, whereas in the indirect route is less than 10-5 % [11].
These properties have a direct impact on the quality of the diagnosis and the therapy. The higher specific activity allows a much better tumour uptake; thus, the dose delivered to the tumour for the same activity is much higher in case of the indirect route, and in addition, the quality of imaging of the tumour is much better [9,10].
The energy of the neutrons in accelerator-based neutron facilities is higher than in thermal reactors. Consequently, experimental data on the 176Yb(n,γ) cross-section in the eV and keV region are mandatory to accurately calculate the production of 177Lu. At present, there is no available experimental 176Yb(n,γ) cross-section data for thermal neutron energies up to 3 keV. In addition, the resonances have not been resolved in the range from 3 to 50 keV.
An experimental campaign at the n_TOF facility provides data from the thermal to the resolved resonance region for the first time, resolving the largest resonances in the 176Yb(n,γ) cross-section. The γ-rays cascade, with a total energy of 5.24 MeV emitted after each capture reaction in 176Yb, have been detected using a set of four C6D6 detectors [12]. The Monte Carlo-based pulse height weighting technique (PWHT) have been in the analysis [13]. These data will be ready to be used in future evaluations of the 176Yb(n,γ) cross-section and for the calculation of 177Lu production in accelerator-based neutron sources as IFMIF-DONES.
Results of the analysis will be shown with particular attention to the possible confirmation of the 1/v behaviour of between thermal resonance region, where there are not experimental data. Furthermore, this measurement will potentially clarify the existence of resonances which have been observed in transmission experiments but were not measured in previous capture measurements.
References:
[1] https://www.euro.who.int/en/health-topics/noncommunicable-diseases/cancer.
[2] Nuclear Physics European Collaboration Committee: nuclear physics for medicine. ISBN: 978-2-36873-008-9. http://www.nupecc.org/pub/npmed2014.pdf.
[3] European Nuclear Society, The Medical Isotope Crisis. http://www.euronuclear.org/1-information/news/medical-isotope-crisis.htm.
[4] NuPEcc. Long Range Plan 2017 Perspectives in Nuclear Physics.
https://www.esf.org/fileadmin/user_upload/esf/Nupecc-LRP2017.pdf.
[5] https://medicis.cern/
[6] K. Kim et al., Lu-177-Based Peptide Receptor Radionuclide Therapy for Advanced Neuroendocrine Tumors, Nucl Med Mol Imag., 2018 Jun; 52(3): 208–215. https://doi.org/10.1007/s13139-017-0505-6.
[7] J. Zhang et al., Clin. Nucl. Med., January 2020, Volume 45, Issue 1, p e48-e50.
https://doi.org/10.1097/RLU.0000000000002655.
[8] A. Dash et al., Production of 177Lu for targeted radionuclide therapy: available options. Nuc. Med. and mol. 1Ima., 49(2):85–107, 2015. https://pubmed.ncbi.nlm.nih.gov/26085854/.
[9] R. Henkelmann, Thursday, 28 February 2013, Lu-177 production with a focus on radiation in the KBA at FRM II, SAAGAS 24, TUM Garching https://indico.frm2.tum.de/event/0/attachments/4/14/Henkelmann_177Lu_gek.pdf.
[10] E. A. M. Ruigrok et al., Extensive preclinical evaluation of lutetium-177-labeledPSMA-specific tracers for prostate cancer radionuclide therapy, Eur. J. Nucl. Med. Mol. Imaging, 2020 Oct 23. 10.1007/s00259-020-05057-6.
[11] K. M. Ferreira et al., Half-life measurement of the medical radioisotope 177Lu produced from the 176Yb(n,γ) reaction. EPJ Web of Conferences Vol 146, pag 08002, EDP Sciences, 2017. https://doi.org/10.1051/epjconf/201714608002.
[12] P. F. Mastinu et al.; New C6D6 detectors: reduced neutron sensitivity and improved safety, (The n_TOF Collaboration), CERN-n TOF-PUB-2013-002 (2013).
[13] U. Abbondanno, G. Aerts et al., New experimental validation of the pulse height weighting technique for capture cross-section measurements, https://doi.org/10.1016/j.nima.2003.09.066.