Biopolymers for the construction of MRI contrast agents

1. Biopolymers for the construction of MRI contrast agents I. Safarik,K. Kluchova,M. Safarikova Institute of Systems Biology and Ecology, Ceske Budejovice, Czech Republic Centre for Nanomaterial Research, Palacky University, Olomouc, Czech Republic

2. Magnetic resonance imaging • Non-invasive method used to render images of the inside of an object • Primarily used in medical imaging to demonstrate pathological or other physiological alterations of living tissues • MRI is currently the most efficient imaging procedure used in medicine

3. Typical MRI device

4. Typical MRI images

5. Problems in MRI • Low contrast between different tissues • Low contrast between a healthy tissue and tumors

6. Contrast agents • Different contrast agents are administered in 40–50% of all MR examinations in order to improve the efficiency of this procedure • Contrast agents are diagnostic pharmaceutical compounds containing paramagnetic or superparamagnetic metal ions or nanoparticles that affect the MR-signal properties of surrounding tissues • Gadolinium chelates are the most widely used extracellular, non-specific contrast agents • Organ specific contrast agents include superparamagnetic iron oxides nanoparticles stabilized with appropriate biopolymers or biocompatible synthetic polymers

7. Clinically approved superparamagnetic contrast agents stabilized with biopolymers • Ferumoxide (Endorem, Feridex)  dextran stabilized • Ferumoxtran (Sinerem, Combidex)  dextran stabilized • Ferucarbotranum (Resovist)  carboxydextran stabilized Used for intravenous applications

8. MRI of liver tumor After SPIO application • Normal liver tissue contains phagocytic Kupffer cells  darkening after dextran-coated SPIO application • Cancer cells do not contain Kupffer cells  after dextran-coated SPIO application tumor is brighter that surrounding tissue Before SPIO application

9. Experimental protein based contrast agents

10. Experimental polysaccharide based contrast agents

11. MRI of gastrointestinal tract Oral application of superparamagnetic nanoparticles Small bowel before (left) and after (right) application of the oral contrast agent

12. MRI of gastrointestinal tract Commercially available contrast agents: • Ferumoxsil (GastroMARK, Lumirem)  silicon-coated superparamagnetic iron oxide • Ferristene (Abdoscan)  sulphonated styrene-divinylbenzene latex particles (Ø3.5 μm) with bound superparamagnetic nanoparticles

13. Our strategy for the development of new oral superparamagnetic MRI contrast agents • Preparation of water-based magnetic fluids and maghemite nanoparticles (by thermally induced oxidative decomposition of iron(II) acetate) • Coating or entrapment of magnetic nanoparticles by chitosan, alginate and agarose in order to prepare biocompatible oral contrast agents • In vitro testing of the prepared materials and comparison with the commercial preparations

14. Contrast agents for MRI of GI tract Idealcontrastagent shouldmeet these criteria: • Goodpatientacceptance • Uniformmarkingof GI tract • Unchangedcharacteristicsofcontrasteffectswhendillutedorconcentratedthroughout theGI tract • No absorptionofcontrastmaterialintothesystemiccirculationoradjacenttissues • Completeexcretionofagent fromGI tract • Increasedsensitivity andspecificityfor diagnosis • Highmarginofsafetyfor thelowesteffectivedose • Acceptablecost

15. In vitro tests

16. I go home today. They cured me using this new miracle drug. I am afraid it’ll be years before it’s approved for humans.