NURA: Radioisotope and radiopharmaceutical · Large scale production of radioisotopes SCK•CENwill join Global Morpho Pharma as shareholder, innovation partner and therapeutic medical

© 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

© SCKCEN, 2018

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

[email protected]

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!

This presentation contains data, information and formats for dedicated use only and may not be communicated, copied,

reproduced, distributed or cited without the explicit written permission of SCK•CEN.

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

right in case of granting a patent or registration in the field of intellectual property.

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