Publicatie Laka-bibliotheek:
Co-ordinated Approach to the Development and Supply of Radionuclides in the EU
| Auteur | N. Mario, A. Kolmayer, G. Turquet, A. Vallée, P.E. Goethals |
 |
6-07-4-60-53.pdf |
| Datum | oktober 2021 |
| Classificatie | 6.07.4.60/53 (ALLERLEI - MEDISCHE ISOTOPEN - NUCLEAIRE GENEESKUNDE ) |
| Opmerking | The objective of the present study was to fill gaps in the available information on the supply chains for the main established and novel radionuclides that have, or are expected to have, significant uses in Europe. The work also had the goal of preparing the ground for long-term European co-operation in this area. The study had to meet the following specific objectives: a. identify the main radionuclides currently in use in the European Union, and the main radionuclides expected to be used by 2030, with a particular focus on the radionuclides used in medicine; b. identify the existing and emerging methods and technologies for production of the radionuclides covered under (a) and fully describe the main elements of their respective supply chains; c. identify the main suppliers of source materials and technologies for production of radionuclides covered under (a) and the facilities which are part of the above supply chains; d. develop scenarios and concrete options for sustainable and secure supply of radionuclides covered under (a) in the EU. |
| Voorkant |
Uit de publicatie:
Executive Summary
According to the new European SAMIRA Action Plan 4, there is a need to secure the
supply of medical radioisotopes in the medium to long term in order to maintain
EU patients’ access to vital medical procedures.
The objective of the present study was to fill gaps in the available information on
the supply chains for the main established and novel radionuclides that have, or
are expected to have, significant uses in Europe. The work also had the goal of
preparing the ground for long-term European co-operation in this area.
The study had to meet the following specific objectives:
a. identify the main radionuclides currently in use in the European Union, and
the main radionuclides expected to be used by 2030, with a particular focus
on the radionuclides used in medicine;
b. identify the existing and emerging methods and technologies for production
of the radionuclides covered under (a) and fully describe the main elements
of their respective supply chains;
c. identify the main suppliers of source materials and technologies for
production of radionuclides covered under (a) and the facilities which are
part of the above supply chains;
d. develop scenarios and concrete options for sustainable and secure supply of
radionuclides covered under (a) in the EU.
Accordingly, among the large number of radionuclides with development potential,
a selection of nuclides has been carried out in consensus with the Steering Group
of this study, and confirmed owing to an analysis of the ongoing clinical trials at a
global level. It turns out that, during the next 2 decades:
- for SPECT imaging, 99m
Tc should continue to be the work-horse;
- for PET imaging: despite high growth expected for 68Ga, 18F should keep its
current leader position; 64Cu, 89Zr and 124I are challengers;
- use of radionuclides for targeted therapy will drastically increase. For the β-
emitters: sharp growth is anticipated for 177Lu, particularly under its non-
carrier added (NCA) form; 131I, 90Y, 223Ra should continue to be largely used.
Use of 166Ho and other RN should develop. R&D progresses for α-emitters
(225Ac, 212Pb, 211At), as well as for new theranostics pairs based on Terbium
and Scandium.
Current and future EU needs for the most important isotopes are quantified.
The isotopes-specific supply chains are analysed in detail, from source material
procurement up to processing of the radiochemical ready for radiopharmaceutical
labelling, to identify the main security of supply challenges that they raise.
Six findings conditioning security of supply are substantiated in this study.
1) Accelerators/cyclotrons and fission/neutron-activation installations are
complementary in the long term, as covering different isotopes-scopes:
a) accelerators/cyclotrons are particularly necessary for accompanying the
anticipated development of PET imaging isotopes and, in a more distant
future, for 225Ac;
b) fission/activation installations are particularly needed for the future
industrial bulk of neutron-activation-produced therapeutic isotopes,
including NCA 177Lu.
2) If reduction of EU reliance on foreign supply is targeted, new investments are
necessary in both domains, cyclotrons/accelerators and fission/activation
installations, as the capability of existing installations to fulfil EU needs will
deteriorate seriously. Indeed, current cyclotrons fleet will be unable to supply
emerging PET isotopes. From 2035 onward, according to the life extension
possibilities of BR2, HFR, Maria and LVR15, reactor’s production capacities will
decline. From 2040, only RJH and FRMII will remain online if no new large
installations are built. Their capacities are unable to cover fully EU needs, not
only for 99Mo, but overall for essential therapeutic β-emitters nuclides such as
NCA 177Lu, 131I, etc.
3) Regarding investments in large installations, several options can be envisaged:
a photonuclear-based installation like SMART or an European version of
Northstar, a fission-based installation like SHINE, a research reactor or a power
reactor. However, the production scopes of the different options are not
equivalent.
a) Whereas a research reactor is able to produce simultaneously, in a proven
and industrial manner, all nuclides generated by fission and neutron
activation, both medical and industrial, it is not the case for developing
options:
i) for SMART, Go/No Go decision is scheduled by end of 2022. SMART would
be able to produce essentially 99Mo and, in the future, certain
accelerator-produced isotopes such as 225Ac. An alternative
photonuclear-based installation, on the model of the US-Northstar using
IBA’s Rhodotron technology could be envisaged as well, but with the
same production scope;
ii) SHINE is currently being licensed in the US only for 99
Mo, 131
I, 133
Xe
production.
b) Using power reactors, particularly CANDU reactors, is an interesting way to
produce isotopes and is being developed in Canada. But not all the operators
are ready to take the risk of perturbing their primary power production in
case of potential malfunctions of the isotopes production. In addition, only
2 CANDU reactors exist in Europe, operated by Nuclearelectrica in Romania,
which currently does not plan to produce other isotopes that 60Co.
4) Other critical points from a security of supply point of view are HALEU supply
and the enrichment of stable isotopes:
a) HALEU is essentially supplied by the US, which anticipate possible shortages
beyond 2030. The ESA Advisory Committee’s Working Group on European
production of low-enriched (19.75%) uranium was re-instated in spring
2021 and mandated to continue the work based on the recommendations
given in the 2019 ESA report. The group will explore the necessary
conditions for establishing European production capacity for HALEU to
respond to the EU needs for the research reactors fuel and medical
radioisotopes production;
b) concerning stable isotopes, achieving satisfactory yields will necessitate the
use of costly enriched targets, which raise a dual problem: their production
and their recycling. Developing cyclotrons radionuclides production will
increase the need for gaseous centrifugation-enriched materials, and
European capabilities will have to be expanded (Urenco, and Orano as
possible new entrant). For other source materials such as enriched 176Yb for
NCA 177Lu production, Russian electromagnetic installations are currently
the main supplier, but with limited capacities. Securing such EMS-enriched
isotopes for the EU would necessitate investments (either in a EU EMS-
enrichment capacity or through the development of alternative
manufacturing routes).
5) Co-ordination between large European research installations is key for
supplying R&D isotopes and promoting new production routes. The PRISMAS-
MAP initiative federates many European research and industrial organizations
for producing R&D and rarer isotopes, on the model of the US National Isotopes
Development Center; such kind of initiatives are to be supported.
6) Life extension and revamping of existing installations is to be considered
whenever possible, as it is currently the case for BR2, HFR, Maria and LVR-15.
Based on these findings, four typical cumulative long-term scenarios are defined.
With regard to their favourable cost-benefit ratio, strong coordination between
large European research installations and life extension of existing installations are
assumed in the four cases. The four scenarios are analysed against a series of
criteria, starting with security of supply.
- Scenario A: EU supply is based on accelerators/cyclotrons and existing
installations, appropriately life-extended whenever possible. In this
scenario, the EU can envisage self-reliance for all imaging isotopes including
the emerging PET isotopes like 68Ga, but not for the main SPECT imaging
isotope 99mTc. Self-reliance can also be envisaged for developing therapeutic
nuclides, namely the α-emitters, but not for the fission/neutron-activated
therapeutic isotopes (NCA 177Lu, etc.), which are the most interesting in the
perspective of beating certain cancers in the next two decades. Import will
then be necessary, and import possibilities of these isotopes will largely
depend upon the success of the North American projects (SHINE, NorthStar,
CANDU, etc.).
- Scenario B.1: In addition to accelerators/cyclotrons, EU supply relies on
large industrial installations based on emerging production routes like
SMART or SHINE. In this case, self-reliance can be envisaged for 99mTc as
well, but not for all therapeutics 5 such as NCA 177Lu. Like in scenario A, EU
will have to rely on imports for these isotopes.
- Scenario B.2: In addition to cyclotrons/accelerators, at least one new
research reactor is built in Europe. In this case, EU self-reliance can be
envisaged for all necessary isotopes, in a proven manner. Such option allows
to maintain the EU export position and open new export opportunities as
well.
- Scenario C: With the addition of own capabilities for HALEU and stable
isotopes enrichment, the EU reduces its reliance on foreign supply to a
minimum.
The second set of criteria deals with investment effort. The number of installations
of each type necessary for achieving EU self-reliance is first evaluated. Using unit
costs for each installation type, orders of magnitude of investments are
established. Though many uncertainties remain for emerging production routes
(CAPEX, production yields, etc.), it turns out that:
- For scenario A, investment could be graded and optimized according to
needs, development of production routes and the opportunities to co-
produce several isotopes in a single installation. However, despite unit costs
being relatively low, new investments in cyclotron installations (SMC & MEC)
would induce very high investments due to the number of installations
needed, especially for short half-life isotope production preventing long-
distance shipping. Corresponding investments could amount to hundreds
5 Pending evidence that SHINE is able to produce them in an efficient manner.
M€ for a new MEC network (~10 MEC) to more than 1 billion € for a full new
SMC network (200 SMC across the EU).
- As cyclotrons/accelerators and large installations are complementary, total
investments are additive. A scenario B.1 unit like SMART could represent a
200-300M€ additional investment, whereas a scenario B.2 new research
reactor could cost more than 1 billion €.
- For scenario C, securing stable isotopes enrichment in the EU, along with
securing HALEU supply would necessitate an additional investment of
several hundred M€.
- However, the optimisation of all these new investments remains to be done,
when more information will be available concerning the market needs and
the performance of the emerging production installations.
Given the complementary production scope of the installations, a large
fission/neutron activation installation remains necessary if reduction of EU
dependence to foreign supply is targeted. Finally, the larger the investment, the
larger the reduction of EU reliance on foreign supply.
Private initiatives can generally be relied upon for graded investments in relatively
low-unit-price cyclotrons. However, such private initiatives are conditional upon
the existence of a market. For large installations (centralized accelerators and
fission-based ones), fully private initiatives might not be practicable, due to the
known difficulty of implementing full cost recovery, the high investment costs
(several hundred M€) and the relatively long durations for design, construction
and licensing (pre-production).
In all cases, due to the many players involved in the investment decisions and the
influence of the global market, the risk of investments not being made in a timely
manner is high. Coping with such situations may thus require a mix of public
incentives and private initiatives 6.
Besides their EU security of supply merits, each scenario also presents other
advantages, namely for maintaining European innovation momentum in many
promising domains.
However, conditioning all four scenarios is the fact that developing nuclear
medicine benefits for beating cancer requires that Europe relies on all the
necessary skills, that nuclear careers become appealing again for students and
that public acceptance is ensured.
Lastly, this study opens up additional subjects of discussion and/or further
investigations. Among others:
- strengthen reliability of input data (EU RN needs, performances and costs
of the diverse technologies and processes, workforce needs, waste
generation, etc.);
- optimize the installations-mix in Europe (cyclotrons, accelerators, large
industrial installations) versus relevant criteria;
- pursue investigations downstream of the supply chain, in the
radiopharmaceutical domain.