Theranostic Terbium Radioisotopes: Challenges in Production for Clinical Application

Abstract

Currently, research on terbium has gained a momentum owing to its four short-lived radioisotopes, 149Tb, 152Tb, 155Tb, and 161Tb, all of which can be considered in one or another field of nuclear medicine. The members of this emerging quadruplet family have appealing nuclear characteristics and have the potential to do justice to the proposed theory of theranostics nuclear medicine, which amalgamates therapeutic and diagnostic radioisotopes together. The main challenge for in vivo use of these radioisotopes is to produce them in sufficient quantity. This review discusses that, at present, neither light charged particle nor the heavy ion (HI) activation are suitable for large-scale production of neutron deficient terbium nuclides. Three technological factors like (i) enrichment of stable isotopes to a considerable level, (ii) non-availability of higher energies in commercial cyclotrons, and (iii) non-availability of the isotope separation technique coupled with commercial accelerators limit the large scale production of terbium radionuclides by light charged particle activation. If in future, the technology can overcome these hurdles, then the light charged particle activation of enriched targets would produce a high amount of useful terbium radionuclides. On the other hand, to date, the spallation reaction coupled with an online isotope separator has been found suitable for such a requirement, which has been adopted by the CERN MEDICIS programme. The therapeutic 161Tb radionuclide can be produced in a reactor by neutron bombardment on enriched 160Gd target to produce 161Gd which subsequently decays to 161Tb. The radiochemical separation is mandatory even if the ISOL technique is used to obtain high radioisotopic purity of the desired radioisotope.

Cutting edge rare earth radiometals: prospects for cancer theranostics

“…152 Tb has been used in combination with 149/155/161 Tb labelled DOTA-conjugates targeting the folate receptor (Chopra 2004 ), in radioimmunoconjugates for targeted α -therapy for malignant melanoma (Rizvi et al 2000 ), and in the first-in-human application for radiotherapy of neuroendocrine tumours as [ 152 Tb]Tb-DOTA-TOC (Baum et al 2017 ). 152 Tb is produced by heavy ion reactions and proton-induced spallation of Ta targets followed by isotopic separation (Allen et al 2001 ), but the production of 152 Tb in quantities useful for clinical applications remains a significant challenge for light charged particle and heavy ion (HI) activation (Naskar and Lahiri 2021 ).…”

Radiolabeled PSMA Inhibitors

“…The additional therapeutic effect of 161 Tb due to Auger electrons was confirmed by a computational approach using a microdosimetry model [ 246 ]. However, despite these very promising results, the production of terbium radioisotopes for clinical application remains challenging [ 247 , 248 ].…”

Excitation functions of deuteron induced nuclear reactions on dysprosium targets for the production of the theranostic relevant isotopes of terbium

“…The growing interest of the scientific community on the terbium family is justified by the fact that it presents four medically relevant radioisotopes, namely 149 Tb, 152 Tb, 155 Tb and 161 Tb, that could be employed either in diagnostic and therapy, and thus becoming a powerful theranostic tool in nuclear medicine [2]. 149 Tb (I α =16.7%, I ec,β + =83.3%, T 1/2 4.118 h [3]) has been proposed for targeted alpha therapy and preclinical studies have been performed [4,5].…”

“…The major challenge for the diffusion of the above-mentioned terbium radioisotopes in the clinical practice is related to the difficulty in obtaining them in high amount (∼ GBq) and with high radionuclidic purity. Comprehensive reviews of the production routes of terbium isotopes have been drawn up by Qaim et al [17] and by Naskar et al [2]. ISOL technique exploits spallation reactions induced by very energetic protons (e.g.…”

“…This technique has been used to obtain enough activity of terbium to perform pre-clinical studies [19]. The drawback of this technique is the very limited number of dedicated facilities [2] like CERN MEDICIS (Medical Isotopes Colleced from ISOLDE) [20] in Switzerland. Only 161 Tb can be produced with (n,γ ) reaction on highly-enriched 160 Gd targets [12].…”