We report the synthesis of novel chelates of Gd and 68Ga with DPTA, DOTA, HP-DOA3, as well as with AAZTA, a novel chelating agent developed by our research group. These chelating agents were appropriately conjugated, prior to metal complexation, with DB58, an RGD peptidomimetic, conformationally constrained on an azabicycloalkane scaffold and endowed with high affinity for integrin a?beta 3. Because a?beta 3 is involved in neo-angiogenesis in solid tumors and is also directly expressed in cancer cells (e.g. glioblastomas, melanomas) and ovarian, breast, and prostate cancers, these constructs could prove useful as molecular imaging probes in cancer diagnosis by MRI or PET techniques. Molecular modeling, integrin binding assays, and relaxivity assessments allowed the selection of compounds suitable for multiple expression on dendrimeric or nanoparticulate structures. These results also led us to an exploratory investigation of 68Ga complexation for the promising 68Ga-PET technique; the AAZTA complex 15(68Ga) exhibited uptake in a xenograft model of glioblastoma, suggesting potentially useful developments with new probes with improved affinity.

Synthesis of Gd and [68Ga] complexes in conjugation with a conformationally-optimized RGD sequence as potential MRI and PET tumour-imaging probes / L. Manzoni, L. Belvisi, D. Arosio, M.P. Bartolomeo, A. Bianchi, C. Brioschi, F. Buonsanti, C. Cabella, C. Casagrande, M. Civera, M. De Matteo, L. Fugazza, L. Lattuada, F. Maisano, L. Miragoli, C. Neira, M. Pilkington-Miksa, C. Scolastico. - In: CHEMMEDCHEM. - ISSN 1860-7179. - 7:6(2012), pp. 1084-1093.

Synthesis of Gd and [68Ga] complexes in conjugation with a conformationally-optimized RGD sequence as potential MRI and PET tumour-imaging probes

L. Belvisi
Secondo
;
A. Bianchi;M. Civera;M. De Matteo;M. Pilkington-Miksa
Penultimo
;
C. Scolastico
Ultimo
2012

Abstract

We report the synthesis of novel chelates of Gd and 68Ga with DPTA, DOTA, HP-DOA3, as well as with AAZTA, a novel chelating agent developed by our research group. These chelating agents were appropriately conjugated, prior to metal complexation, with DB58, an RGD peptidomimetic, conformationally constrained on an azabicycloalkane scaffold and endowed with high affinity for integrin a?beta 3. Because a?beta 3 is involved in neo-angiogenesis in solid tumors and is also directly expressed in cancer cells (e.g. glioblastomas, melanomas) and ovarian, breast, and prostate cancers, these constructs could prove useful as molecular imaging probes in cancer diagnosis by MRI or PET techniques. Molecular modeling, integrin binding assays, and relaxivity assessments allowed the selection of compounds suitable for multiple expression on dendrimeric or nanoparticulate structures. These results also led us to an exploratory investigation of 68Ga complexation for the promising 68Ga-PET technique; the AAZTA complex 15(68Ga) exhibited uptake in a xenograft model of glioblastoma, suggesting potentially useful developments with new probes with improved affinity.
Chelates; Imaging agents; Integrins; RGD; Tumor targeting
Settore CHIM/06 - Chimica Organica
Article (author)
File in questo prodotto:
Non ci sono file associati a questo prodotto.
Pubblicazioni consigliate

Caricamento pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/174914
Citazioni
  • ???jsp.display-item.citation.pmc??? 9
  • Scopus 41
  • ???jsp.display-item.citation.isi??? 41
social impact