High sensitivity MR imaging reporters (paramagnetic complexes, CEST, hyperpolarized molecules)
Silvio Aime
silvio.aime@unito.it

 

Description

The main lines of research activities are the following:

  • synthesis and MRI assessment of high-relaxivity Gd-based chelates (including multimeric derivatives and nano-sized assemblies);
  • synthesis and MRI assessment of novel agents based on chemical exchange saturation transfer (CEST);

  • development of MRI- 13C-hyperpolarised molecules via the formation of para-hydrogenated substrates;

  • Imaging reporters responsive to specific physicochemical and biological parameters of the cellular microenvironment (pH, temperature, metabolites' concentration, enzymatic activity)

  • Cellular labelling (stem cells, leukocytes, tumour cells, etc.) by the internalisation of paramagnetic metal chelates;

  • Tumor “targeting” (AA, LDL, Anionic and cationic transporters, Adhesion molecules, Hyperexpressed receptors, fibrin…)

  • Targeting thrombi and plaques with suitably functionalised nanocarriers bearing different types of imaging reporters.

  • Multiple Sclerosis

  • Assessment of changes in Vascular Permeability in neo-formed vessels

 

Selected publications

 

  1. Terreno, E; Delli Castelli, D; Violante, E; Sanders, HMHF; Sommerdijk, NAJM; Aime, S, Osmotically Shrunken LIPOCEST Agents: An Innovative Class of Magnetic Resonance Imaging Contrast Media Based on Chemical Exchange Saturation Transfer, CHEMISTRY-A EUROPEAN JOURNAL, 15 (6): 1440-1448 2009

  2. Baranyai, Z; Uggeri, F; Giovenzana, GB; Benyei, A; Brucher, E; Aime, S, Equilibrium and Kinetic Properties of the Lanthanoids(III) and Various Divalent Metal Complexes of the Heptadentate Ligand AAZTA, CHEMISTRY-A EUROPEAN JOURNAL, 15 (7): 1696-1705 2009

  3. Digilio, G; Catanzaro, V; Fedeli, F; Gianolio, E; Menchise, V; Napolitano, R; Gringeri, C; Aime, S, Targeting exofacial protein thiols with Gd-III complexes. An efficient procedure for MRI cell labelling, CHEMICAL COMMUNICATIONS, (8): 893-895 2009

  4. Stefania, R; Tei, L; Barge, A; Geninatti Crich, S; Szabo, I; Cabella, C; Cravotto, G; Aime, S, Tuning Glutamine Binding Modes in Gd-DOTA-Based Probes for an Improved MRI Visualization of Tumor Cells, CHEMISTRY-A EUROPEAN JOURNAL, 15 (1): 76-85 2009

  5. Chaabane, L; Adage, T; Aime, S; Greco, B; Zaratin, P, Differential degree of blood-brain barrier permeability during experimental autoimmune encephalomyelitis measured by gadolinium-enhancement magnetic resonance imaging, MULTIPLE SCLEROSIS, 14: S100-S100 Suppl. 1 SEP 2008

  6. Esposito G, Geninatti Crich S, Aime S, Efficient cellular labeling by CD44 receptor-mediated uptake of cationic liposomes functionalized with hyaluronic acid and loaded with MRI contrast agents, ChemMedChem. 2008 Dec;3(12):1858-62.

  7. Reineri F, Viale A, Giovenzana G, Santelia D, Dastrù W, Gobetto R, Aime S, New hyperpolarized contrast agents for 13C-MRI from para-hydrogenation of oligooxyethylenic alkynes.
    J Am Chem Soc. 2008 Nov 12;130(45):15047-53.

  8. Battistini E, Gianolio E, Gref R, Couvreur P, Fuzerova S, Othman M, Aime S, Badet B, Durand P, High-relaxivity magnetic resonance imaging (MRI) contrast agent based on supramolecular assembly between a gadolinium chelate, a modified dextran, and poly-beta-cyclodextrin
    Chemistry A European Journal. 2008;14(15):4551-61.

  9. Datta A, Hooker JM, Botta M, Francis MB, Aime S, Raymond KN, High relaxivity gadolinium hydroxypyridonate-viral capsid conjugates: nanosized MRI contrast agents.
    J Am Chem Soc. 2008 Feb 27;130(8):2546-52.

  10. Terreno E, Barge A, Beltrami L, Cravotto G, Castelli DD, Fedeli F, Jebasingh B, Aime S.
    Highly shifted LIPOCEST agents based on the encapsulation of neutral polynuclear paramagnetic shift reagents.
    Chem Commun (Camb). 2008 Feb 7;(5):600-2.

  11. Gianolio E, Giovenzana GB, Ciampa A, Lanzardo S, Imperio D, Aime S.
    A novel method of cellular labeling: anchoring mr-imaging reporter particles on the outer cell surface.
    ChemMedChem. 2008 Jan;3(1):60-2.

  12. Viale, A, Santelia, D; Napolitano, R; Gobetto, R; Dastru, W; Aime, S, The Detection of PHIP Effects Allows New Insights into the Mechanism of Olefin Isomerisation during Catalytic Hydrogenation, EUROPEAN JOURNAL OF INORGANIC CHEMISTRY, (28): 4348-4351 OCT 2008

  13. Castelli, DD; Gianolio, E; Crich, SG; Terreno, E; Aime, S, Metal containing nanosized systems for MR-Molecular Imaging applications, COORDINATION CHEMISTRY REVIEWS, 252 (21-22): 2424-2443, 2008

  14. Tsotsalas, M; Busby, M; Gianolio, E; Aime, S; De Cola, L ,Functionalized nanocontainers as dual magnetic and optical probes for molecular imaging applications, CHEMISTRY OF MATERIALS, 20 (18): 5888-5893 SEP 23 2008

  15. Geninatti Crich, S; Lanzardo, S; Alberti, D; Belfiore, S; Ciampa, A; Giovenzana, GB; Lovazzano, C; Pagliarin, R; Aime, S, Magnetic resonance imaging detection of tumor cells by targeting low-density lipoprotein receptors with Gd-loaded low-density lipoprotein particles, NEOPLASIA, 9, 1046-1056, 2007.
     
  16. Terreno E, Cabella C, Carrera C, Delli Castelli D, Mazzon R, Rollet S, Stancanello J, Visigalli M, Aime S. “From Spherical to Osmotically Shrunken Paramagnetic Liposomes: An Improved Generation of LIPOCEST MRI Agents with Highly Shifted Water Protons” Angew Chem Int Ed Engl. 46 (6): 966-968 2007

  17. Aime S, Castelli DD, Lawson D, Terreno E, Gd-loaded liposomes as T-1, susceptibility, and CEST agents, all in one, JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 129 (9): 2430-+ MAR 7 2007

  18. Assfalg, M; Gianolio, E; Zanzoni, S; Tomaselli, S; Lo Russo, V; Cabella, C; Ragona, L; Aime, S; Molinari, H, NMR structural studies of the supramolecular adducts between a liver cytosolic bile acid binding protein and Gadolinium(III)-chelates bearing bile acids residues: Molecular determinants of the binding of a hepatospecific magnetic resonance Imaging contrast agent, JOURNAL OF MEDICINAL CHEMISTRY, 50 (22): 5257-5268 NOV 1 2007

  19. Bussolati, B; Grange, C; Tei, L; Deregibus, MC; Ercolani, M; Aime, S; Camussi, G, Targeting of human renal tumor-derived endothelial cells with peptides obtained by phage display, JOURNAL OF MOLECULAR MEDICINE-JMM, 85 (8): 897-906 AUG 2007

  20. Gianolio, E; Giovenzana, GB; Longo, D; Longo, I ; Menegotto, I; Aime, S, Relaxometric and modelling studies of the binding of a lipophilic Gd-AAZTA complex to fatted and defatted human serum albumin, CHEMISTRY-A EUROPEAN JOURNAL, 13 (20): 5785-5797 2007

  21. Himmelreich U, Aime S, Hieronymus T, Justicia C, Uggeri F, Zenke M, Hoehn M, A responsive MRI contrast agent to monitor functional cell status, NEUROIMAGE 32 , 1142-1149, 2006

  22. Aime S, Crich SG, Gianolio E, Giovenzana GB, Tei L, Terreno E High sensitivity lanthanide(III) based probes for MR-medical imaging, COORDINATION CHEMISTRY REVIEWS 250, 1562-1579, 2006

  23. Geninatti Crich S, Cabella C, Barge A, Belfiore S, Ghirelli C, Lattuada L, Lanzardo S, Mortillaro A, Tei L, Visigalli M, Forni G, Aime S.
    In vitro and in vivo magnetic resonance detection of tumor cells by targeting glutamine transporters with Gd-based probes.
    J MED CHEM 2006, 49 (16), 4926-36.

  24. Geninatti Crich S, Bussolati B, Tei L, Grange C, Esposito G, Lanzardo S, Camussi G, Aime S
    Magnetic resonance visualization of tumor angiogenesis by targeting neural cell adhesion molecules with the highly sensitive gadolinium-loaded apoferritin probe
    CANCER RES 2006, 66 (18), 9196-201.

  25. Bussolati B, Grange C, Bruno S, Buttiglieri S, Deregibus MC, Tei L, Aime S, Camussi G
    Neural-cell adhesion molecule (NCAM) expression by immature and tumor-derived endothelial cells favors cell organization into capillary-like structures
    EXP CELL RES 2006, 312(6), 913-24.

  26. Aime S, Frullano L, Geninatti Crich S.
    Compartmentalization of a gadolinium complex in the apoferritin cavity: a route to obtain high relaxivity contrast agents for magnetic resonance imaging
    ANGEW CHEM INT ED ENGL 2002, 41, 1017-9.

  27. S. Aime, M. Fasano, E. Terreno, M. Botta, Protein-Bound Metal Chelates, in “The Chemistry of Contrast Agents in Medical Magnetic Resonance Imaging” (Eds.: A. E. Merbach, E. Toth), John Wiley & Sons, LTD, Chichester, 2001, chap. 5, pp. 193-241.

  28. Aime S, Barge A, Gianolio E, Pagliarin R, Silengo L, Tei L, High relaxivity Contrast Agents for MRI and Molecular Imaging, in “Molecular Imaging: an essential tool in preclinical research, diagnostic imaging and theraphy" Series: Erns Schering Research workshop, Bogdanod A and Licha K (eds) 2004, vol. 49.

  29. Aime S., Barge A., Gianolio E., Geninatti Crich S., Dastrù W., Uggeri F. Paramagnetic Metal complexes as Contrast Agents for Magnetic Resonance Imaging, in “Metallotherapeutic Drugs & Metal-based Diagnostic Agents” M. Gielen and E.R.T. Tiekink (eds) John Wiley & Sons, Ltd, 2005, 541-559.

  30. S. Aime, G.B. Giovenzana, D. Longo, E. Terreno, Design of Contrast Agents for Molecular Imaging In Vivo. in “In Vivo MR Techniques in Drug Discovery and Development” (Ed. N. Beckmann), Taylor & Francis, New York, 2006, chap. 4, pp. 47-72.

  31. Aime S., Baranyai Z., Gianolio E., Terreno E. Paramagnetic Contrast Agents in “Molecular and Cellular MR-Imaging” M.M.J.J. Modo and J. Bulte (ed.)
     


     

 

Unit members

 

  Terreno  Enzo associate professor enzo.terreno@unito.it
  Dastrù  Walter researcher walter.dastru@unito.it
  Geninatti Crich Simonetta researcher simonetta.geninatti@unito.it
  Gianolio Eliana researcher eliana.gianolio@unito.it
  Viale  Alessandra researcher alessandra.viale@unito.it
  Reineri Francesca researcher francesca.reineri@unito.it
  Delli Castelli   Post doctoral fellow daniela.dellicastelli@unito.it
  Longo Dario Post doctoral fellow dario.longo@unito.it
  Stefania  Rachele Post doctoral fellow rachele.stefania@unito.it
  Menchise  Valeria Post doctoral fellow valeria.menchise@unito.it
  Catanzaro Valeria Post doctoral fellow valeria.catanzaro@unito.it
  Cittadino Evelina phD student evelina.cittadino@unito.it
  Torres Elena phD student elena.torres@unito.it
  Arena Francesca phD student francesca.arena@unito.it
  Alberti Diego phD student  
  Meinini Francesco Graduate student francesco.meinini@tin.it
  Bianco Carlotta Undergraduate student carlotta_bianco@yahoo.it
  Di Gregorio Enza Undergraduate student  
  Ferrauto Giuseppe Undergraduate student  
  Porto Silvia Post doctoral fellow  
  Kalman Ferenc Post doctoral fellow ferkoka26@yahoo.com 
  Szabo Ibolya Post doctoral fellow ibolya23@freemail.hu 
  Figuereido Sara phD student  
    Jebasingh Post doctoral fellow  
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