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
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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
Slide2Slide3Aim 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
Slide4Development 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;
Slide5Obtain 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
Slide6Joint 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
Slide77
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.
Slide844Sc 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
Slide9Thank you!9
Slide1044
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
Slide11J.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
Slide1212Kopa 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
Slide13MD4-155Tb – Mid August 20186.9GBq 24h pec iradiacijas (EOB)Extracted pec 5d49.7MBqEfektivitate ekstrakcijai 1,2%
ISOL tehnika 13