© SCKCEN, 2018
NURA: Radioisotope and
radiopharmaceutical
development at SCK•CEN
Maarten Ooms [email protected]
© SCKCEN, 2018
Outline
Introduction to NURA
Radioisotope development at SCK•CEN
Radiopharmaceutical development at SCK•CEN
© SCKCEN, 2018
Pre-clinical services to assist in the
development of new therapeutic
radiopharmaceuticals (i.e. proof-of-
concept/impact assessment).
Developing and strengthening
SCK•CEN’s research
further within the Nuclear Medicine
applications.
3
Radiopharmaceutical research
Radiochemistry/Radiopharmacy
Radiobiology
Dosimetry
C
R
O
Sustainable supply of relevant
therapeutic radio-isotopes and
radiopharmaceuticals.
Radioisotope production at SCK•CEN
GMP quality Sufficient
quantities
Continuous supply and backup
C
M
O
Rese
arc
h
A dedicated program at SCK•CEN focusing on radiopharmaceutical research
and manufacturing of medical radioisotopes and radiopharmaceuticals
NURA
© SCKCEN, 2018
NURA infrastructure
BR2 Reactor MYRRHA project
Radiopharmacy labs
© SCKCEN, 2018
Radioisotope of interest
225Ac
188Re
161Tb 213Bi
177Lu
153Sm
Production
R&D levels
© SCKCEN, 20186
Global Morpho Pharma will focus initially on the production and distribution of industrial quantities of non-carrier added Lutetium-177 (ncaLu-177) and Actinium-225 free of long lived impurities.
Large scale production of radioisotopes
SCK•CEN will join Global Morpho Pharma as shareholder, innovation partner and therapeutic medical radionuclides manufacturer.
SCK•CEN and IRE Elit are
joining forces to establish
a reliable supply of GMP
grade nca Lu-177 in
Europe and beyond.
GMP grade
• nca 177Lu
• 225Ac
© SCKCEN, 2018
Actinium-225: current status
Historical 229Th capsule 225Ac purification
Only a few mCi of 229Th available
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226Ra stock at SCK•CEN
German – Belgian project on 227Ac production (heat source for
space applications)
Neutron irradiation of dozens of grams of 226Ra in BR2!
Extensive amount of 226Ra is still at SCK•CEN
© SCKCEN, 2018
Large scale Actinium-225 production at SCK•CEN?
226Ra(p,2n) 225Ac 226Ra(γ,n) 225Ra 225Ac
Handling of Rn-222 gas Target preparation Separation method Ra-226/Ac-225
© SCKCEN, 2018
Bismuth-213
© SCKCEN, 2018
Terbium-161
Production Processing
160Gd (n,γ) 161Gd 161Tb
161TbCl3 ready to radiolabel
160Gd/161Tb
161Tb
161TbCl3Radionuclidic Purity >99.99%
Isotopic Purity – ICPMS underway
Radiochemical - Underway
© SCKCEN, 2018
Novel separation techniques for Terbium
Tb4+
Tb4+
Tb4+
Tb4+
Ln3+ mixture Tb oxidation
Isolation of Tb4+
Tb3+
Gd3+
Dy3+
Tb3+
Tb3+
Meryem Arman
© SCKCEN, 2018
Samarium-153
153Sm/154Eu
mixture
154Eu 153Sm
SILP packing
Ionic Liquid phase extraction
Supported Ionic Liquid phase extraction
Michiel Van de Voorde
Van de Voorde et al., RSC Adv, 2018
Patent application: PCT/EP2018/078528
© SCKCEN, 2018
Rhenium-188
186W (2n,γ) 188W 188Re
Ponsard et al., J Radioanal Nucl Chem, 2003
© SCKCEN, 2018
Radiopharmaceutical research within NURA
R&D towards production of new radioisotopes
Irradiation
Separation techniques
R&D towards development of radiopharmaceuticals
Development of optimal bifunctional chelators for radiolabeling
Combining new chelators with a wide variety of carrier molecules
Antibody
Nanobody
Nano or magnetic
particles
Peptide
© SCKCEN, 2018
213Bi radiolabeled nanobodies
16 16 Cancer cell
Nanobody
HER2-Receptor
213Bi
Bifunctionalchelator
Conventional Antibody(150 kDa)
Nanobody(15 kDa)
Yana Dekempeneer
© SCKCEN, 2018
213Bi radiolabeled nanobodies
213Bi-DTPA-HER2
Blood
Hea
rt
Lung
Live
r
Kidne
ys
Sm
all int
estin
e
Larg
e inte
stine
Bon
e
Tumor
0
20
40
60
8015 min
30 min
60 min
%ID
/g
High Kidney retention
Max tumor uptake: 7,2 %ID/g (30 min)
Radiolabeling Ex vivo evaluation
0 50 100 150 mm
TLC
0 50 100 150 mm
0
100
200
300
400
500
600
700
800
900 C/mm
Reg
#1
Reg
#2
[213Bi]DTPA-
(HER2
nanobody)
98%
[213Bi]
2%
In vitro evaluation
0 50 100 1500
20
40
60
80
100
Saline (37°C)
Mouse Serum (37°C)
Time (min)
% in
tact
0.01 0.1 1 10 100 10000
200
400
600
800
1000
1200
[Ligand]
Sp
ecific
bin
din
g (
nM
)
© SCKCEN, 2018
Development of 161Tb radiolabeled radiopharmaceuticals
Irwin Cassells
0,1 1 5 10
0
20
40
60
80
100
Chelator concentration (µM)
Rad
ioch
em
ical Y
ield
(%
)
DOTA
Tb-IRMA-V
BR2MEDICIS
© SCKCEN, 2018
Radioisotopes and radiopharmaceuticals at SCK•CEN
225Ac
188Re
161Tb 213Bi
177Lu
153Sm
© SCKCEN, 2018
Copyright © 2018 - SCKCEN
PLEASE NOTE!
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If this explicit written permission has been obtained, please reference the author, followed by ‘by courtesy of SCK•CEN’.
Any infringement to this rule is illegal and entitles to claim damages from the infringer, without prejudice to any other
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SCK•CEN
Studiecentrum voor Kernenergie
Centre d'Etude de l'Energie Nucléaire
Belgian Nuclear Research Centre
Stichting van Openbaar Nut
Fondation d'Utilité Publique
Foundation of Public Utility
Registered Office: Avenue Herrmann-Debrouxlaan 40 – BE-1160 BRUSSELS
Operational Office: Boeretang 200 – BE-2400 MOL