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Magnetotheranostics January 2017
Magnetotheranostics:
From Superparamagnetic Nano-particles until Tools for Detection
and Treatment of Cancer
Motivation:
Lymph node status is one of the most important prognostic factors
for prostate cancer
Early and complete lymph node staging is a big challenge for a
successful treatment
Major goals:
High-resolution MRI with superparamagnetic nanoparticles allows
detection of otherwise undetectable lymph node metastases.
Targeted treatment of metastases by hyperthermia
Research tasks:
Based on existing SPION-coating systems development of
SPION antibody systems
Specific adsorption of nanoparticles as MRI contrast agent
(molecular imaging)
In-vivo behaviour of SPION-Antibody-complexes
Dedicated software needs to be developed to perform
treatment planning and assisting hardware design
New compositions:
ZnFe2O4; Ca, Mg, Mn or Ti doped Fe2O3; V doped TiO2;
Mn doped ZnO; Fe doped Al2O3 and TiO2).
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Magnetotheranostics January 2017
IONP for MRI
20 nm IONP shows a very high relaxivity (high contrast) at 3Tesla clinical MRI
Further development of ultra-short echo time (UTE) MRI imaging.
Transfer of the sequences to partners
Diffusion-weighted MRI sequences alone and in combination with SPION for the detection of
lymph node metastases were further developed and the software for the processing of
diffusion-weighted MRI (mono-/bi- exponential model fitting) was developed.
Small lymph nodes (3 mm diameter) are detectable by MRI with SPION as contrast agents
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Magnetotheranostics January 2017
Functionalization with targeting molecules
3 candidate ligands targeting the extracellular part of Prostate-specific membrane antigen (PSMA)
transmembrane receptor were chosen:
(i) Small urea molecule ACUPA (phase II clinical trial for docetaxel nanoparticles)
(ii) Aptamer A10 (phase I clinical trial for docetaxel-loaded nanoparticles)
(iii) Antibody J591 (phase II trials for PC immunotherapy, radiotherapy, imaging)
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Magnetotheranostics January 2017
In vivo tumor model
Most promising model: Grafting of MAT-LyLu prostate metastatic cell line in the rat.
Method: Incubation of MAT-LyLu with fluorescent aptamer-Cy5 and small molecule-BDP FL
aptamer-Cy5
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Magnetotheranostics January 2017
Task 2: Nano particle hyperthemia applicator
prototype
Field coils Amplifiers
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Magnetotheranostics January 2017
Simulation Platform for TP
multiscale, multiphysics nanoparticle HT modeling:
electromagnetic field induced heating (incl. thermoregulation)
therapeutic impact
image integration: SPION density & anatomy for personalized
simulations,
novel FEM thermal solver with inhomogeneous & anisotropic
tissue models (perfusion & effective thermal conductivity)
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Magnetotheranostics January 2017
Example: Modeling of dog NP HT
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Magnetotheranostics January 2017
Conclusion
Milestones and delivery fulfilled as planned
Animal models and antibodies selected and tested
biological/medical part already started.
Next steps:
Finalizing animal tests
in vitro tets Tests of the magnetic field generator with INOP of
this project
Establishing of SOP for synthesis, modification, testing and
application of all products developed in Magnetotheranostics
Evaluation of GMP production of core nanoparticles ( 300 kCHF
for accereditation of the process, in contact with 3 companies)
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Magnetotheranostics January 2017
Disseminationofresults
Besidescientificpublicationswe
presentedourresultsalsotothe
public:
NanoWorldCancerDay2016
UniversityHospitalZurich
NanoWorldCancerDay2017,
UniversityofGeneva
"Imaginez unmonde,
http://www.rts.ch/play/tv
Dbora Bonvin,PhDstudent My
Thesisin180Secondscontest.
http://www.rts.ch/play/tv/lecourt
dujour/video/3minutespourla
sciencedeborabonvin?id=8078641
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MagnetotheranosticsJanuary2017
Thankyouforyourattention
Investigator Institution Maintask
H.Hofmann,D.Bonvin, EPFL Particle andfunctionalisation
MMionic
B.vonRechenberg P. Vetsuisse Zrich animalexperiments
Kircher,
H.Richter
H.Thoeny, Inselspital,Bern MRIoflymph node
S.Barbieri, metastasis
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MagnetotheranosticsJanuary2017