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44 Sc production with 18 MeV cyclotron and 44 Sc production with 18 MeV cyclotron and

44 Sc production with 18 MeV cyclotron and - PowerPoint Presentation

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44 Sc production with 18 MeV cyclotron and - PPT Presentation

joint study of scandiumlabeled peptide based ligands for clinical use Assocprof Maija Radzina R ī ga Stradi ņš U niversity Radiology Research laboratory Mgchem ID: 809735

cyclotron 44sc amp target 44sc cyclotron target amp production clinical radionuclide protons based imaging neuroendocrine study pet medicine medicis

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Slide1

44Sc production with 18 MeV cyclotron and joint study of scandium-labeled peptide based ligands for clinical use

Assoc.prof. Maija Radzina, Rīga Stradiņš University, Radiology Research laboratory Mg.chem. Edgars Mamis, Rīga Stradiņš University, Nuclear Medicine Clinic

Slide2

Slide3

Aim of the project –

joint reserach activityThe goals of this project are:To develop economically efficient middle energy (18 MeV) cyclotron based technology for production and purification of 44Sc radionuclide as a medical diagnostic isotope in comparison with generator based technologyTo provide clinical study platform for 44Sc radionuclide based imaging in neuroendocrine tumorsTheranostic pairing – 44Sc + 47

Sc and their validation in

middle energy cyclotron based technology

3

Slide4

Development of technology

Develop economicaly efficient cyclotron manufactured 44Sc as a diagnostic radionuclide and labeling technique 44Sc liquid and solid target design and adjustment for 44Sc production with 18 MeV cyclotron;4

Production and optimization of

44

Sc production using solid target versus using liquid target

;

Transfer of crude

44

Sc from cyclotron to “hot lab” from solid target versus from liquid target;

Slide5

Obtain pure, non-carrier added 44Sc

by chemical purification versus mass separation with the help of MEDICIS;Quality check of cyclotron-produced and purified 44Sc against reference sample of 44Sc from MEDICIS;Develop technology and method for radiolabeling of DOTA conjugated peptide (TOC & TATE) with 44Sc. P

roduct

purification and formulation;

Quality control – physical and chemical analysis of

44

Sc-DOTA

conjugated peptide

-

based

ligand

for cancer diagnostics;

5

Phase I activities

may

be initiated by

the

beginning of

2019

Slide6

Joint Clinical research platform

Verification of use in clinical medicine – 2020/2021neuroendocrine tumour patients for clinical validation of 44Sc-DOTATOCUnknown primary NENStage 3 and 4 NEN licenced medical PET/CT facility of RSU Nuclear medicine clinic is able to perform in-human imaging studies and host the clinical study with 44Sc- DOTA peptides and cancer binding active substances on a neuroendocrine malignancy patient cohort for the proof of concept

Interest

for

Theranostic

pairing

44

Sc +

47

Sc and their validation in neuroendocrine tumors and possibly other malignancy groups

6

Slide7

7

2. Study with Theranostic pairing – 44Sc + 47Sc and their validation in neuroendocrine tumors and possibly other malignancy groupsFuture Perspectives

V

erification

of use in clinical

medicine

Singh

,

Aviral

&

van

der

Meulen

,

Nicholas

&

Müller

,

Cristina

&

Klette

,

Ingo

&

Kulkarni

,

Harshad

&

Türler

, Andreas &

Schibli

,

Roger

&

Baum

, Richard P.. (2017). First-

in

-

Human

PET/CT

Imaging

of

Metastatic

Neuroendocrine

Neoplasms

with

Cyclotron-Produced

44

Sc

-DOTATOC: A

Proof-of-Concept

Study

.

Cancer

Biotherapy

and

Radiopharmaceuticals

. 32. 124-132. 10.1089/cbr.2016.2173.

Slide8

44Sc is a

promising radionuclide for positron emission tomography (PET/CT) with with 177Lu, 90Y, or 47Sc as therapeutic counterparts144Scdue to the half life (T1/2 = 3.92h) almost 4 times longer than half life of 68Ga (T

1/2 = 67.71 min) it

is an attractive candidate for development of novel PET-radiopharmaceuticals.

47

Sc

can

be utilized in radiotherapy using the same vector molecules

8

1

Hoehr

C., at. al.

44gSc production using a water target on a 13 MeV cyclotron, Nuclear Medicine and Biology 41, 2014, 401 – 406;

Mean range in tissue

47

Sc

- 810 µm

177

Lu – 670 µm

90

Y – 3900 µm

44

Sc and

47

Sc as matched pair for molecular imaging

Matched Radionuclide Pairs for Imaging and Therapy (edited by A. Bockish) Eur J Nucl Med Mol Imaging, Vol 38, Suppl 1, June 2011

Slide9

Thank you!9

Slide10

44

Sc – 3,92 h 44Ca(p,n)44ScCyclotron production of 44Sc

44m

Sc – 58,6

h

44

Ca(p,n)

44m

Sc

44

Sc

44

Sc

44m

Sc

44m

Sc

Data for activity calculation

intensity – 2

μ

A

time – 30 min

44

CaCO

3

target – 100 mg

Levkovskij,

Act.Cs.By Protons and Alphas,

Moscow 1991

,

USSR

ichtj

Abbas et al. Cyclotron production of

44

Sc - new radionuclide for PET technique.

19th International Symposium on Radiopharmaceutical Sciences. 28.08-2.09.2011, Amsterdam

Slide11

J.P. Ramos11Schedule target

irradiation and isotope separationISOLDE, MEDICIS projektiInzenieris#644M-Ta-Re total protons 6.9E18Target life time defined in protons (5E18 to 1E19 protons)149Tb152Tb155Tb149Tb Shipped to CHUV 1,0 MBq 149Gd155Tb646-Ta-W total protons 6E18155Tb155Tb shipped to NPL 40 MBq 39Ce647M-Ta-Re protons 3.1E18, on-going<1%149Tb 4,1 MBq, gal’a 81MBq 133Ce, pirmais MEDICIS Beam

Slide12

12Kopa 6 targets1,7E19 protonsAizsutiti

uz iestadem13 collections-5MDJo augstaka T, jo vairak dabu protonus 2200-2300C, paaugstina Tb aktivitatiTarget reuse does not influnce in the activities (5x)Target reaches their life-time

Slide13

MD4-155Tb – Mid August 20186.9GBq 24h pec iradiacijas (EOB)Extracted pec 5d49.7MBqEfektivitate ekstrakcijai 1,2%

ISOL tehnika 13