Rhenium-188 Radiochemistry: Challenges and Prospects

Abstract

After a lull in development of new chemistry for rhenium-188 and technetium-99m since 2000, there has been new investment in production facilities for Mo-99/Tc-99m coupled with increasing interest in rhenium-188 radionuclide therapy, particularly in developing countries. Much of the chemistry developed in the 1990s is not readily amenable to supporting modern radiopharmaceutical development, which places increased emphasis on molecular targeted radiopharmaceuticals. Consequently there is a need for new radiolabelling chemistry to incorporate these radionuclides into biomolecules using simple, kit-based methodology. This review provides an update on progress towards simple rhenium-188 labelling methods since 2000.

Bifunctional chelators for radiorhenium: past, present and future outlook

“…Although these radioisotopes could not be more different in terms of the attention they have received, technetium and rhenium have many chemical and structural similarities with regards to complex formation as they are group 7 congeners. 25,27,36,50 Because of these similarities, and the fact that there exists no non-radioactive isotope of technetium, "cold" rhenium has often been used as a replacement for 99m Tc for nonradioactive characterisation and mechanistic elucidation purposes. 29,34,50 Similarly, 99m Tc radiopharmaceuticals may serve as a model for the preparation of novel 186/188 Re radiotherapeutics, allowing for the formation of isostructural complexes of the different isotopes.…”

“…This was largely due to the global shortage at that time of 99 Mo, the parent radionuclide for the production of 99m Tc, leading to a concomitant crisis in the field of nuclear chemistry. 25,34 Focus was therefore shifted to the use of more convenient chemical isotopes, such as the β-emitting radionuclides 90 Y and 177 Lu, both of which can be developed at high capacities and do not require elaborate chelator chemistry. 25,34 Although this took the focus off of 186 Re and 188 Re for some time, there has been a resurgence in interest in these radioisotopes in the past decade, as was predicted by Blower in 2017.…”

“…25,34 Focus was therefore shifted to the use of more convenient chemical isotopes, such as the β-emitting radionuclides 90 Y and 177 Lu, both of which can be developed at high capacities and do not require elaborate chelator chemistry. 25,34 Although this took the focus off of 186 Re and 188 Re for some time, there has been a resurgence in interest in these radioisotopes in the past decade, as was predicted by Blower in 2017. 25 While this deceleration of the downward trend observed in the popularity of radiorhenium is a good start, the acceptance for rhenium isotopes is nowhere near where it once was, nor where it could be.…”

“…Over the past decade, many interesting and comprehensive reviews on the different types of BFCs for radiorhenium in the context of TRNT have been written. 13,18,[22][23][24][25] In fact, in 2017 an entire special issue by the International Journal of Nuclear Medicine and Research was dedicated to the use of 188 Re in radionuclide therapy. 26 The purpose of this review is to provide a brief summary of some of the most notable chelators, as well as give an up-to-date…”

Rhenium-188 Labeled Radiopharmaceuticals: Current Clinical Applications in Oncology and Promising Perspectives

“…Perrhenate is much more difficult to reduce than pertechnetate, which is of prime importance, since this is the form obtained from the generators. This rich but difficult chemistry—which has been thoroughly reviewed recently and do not enter the scope of this review (26), coupled with the current limited availability of pharmaceutical-grade rhenium-188, may explain why 188 Re-radiopharmaceuticals have not yet gained wide acceptance, while the use of more convenient therapeutic isotopes (simple, straightforward chemistry, and high production capacities), such as 90 Y and 177 Lu, is steadily increasing. This is clearly visible when making a bibliographical search on these isotopes, combined with “clinical” research term (Figure 1), despite the expected considerably higher costs.…”