title: Caspase-responsive smart gadolinium-based contrast agent for magnetic resonance imaging of drug-induced apoptosis.
abstract: Non-invasive detection of caspase-3/7 activityin vivohas provided invaluable predictive information regarding tumor therapeutic efficacy and anti-tumor drug selection. Although a number of caspase-3/7 targeted fluorescence and positron emission tomography (PET) imaging probes have been developed, there is still a lack of gadolinium (Gd)-based magnetic resonance imaging (MRI) probes that enable high spatial resolution detection of caspase-3/7 activityin vivo. Here we employ a self-assembly approach and develop a caspase-3/7 activatable Gd-based MRI probe for monitoring tumor apoptosis in mice. Upon reduction and caspase-3/7 activation, the caspase-sensitive nano-aggregation MR probe (C-SNAM:1) undergoes biocompatible intramolecular cyclization and subsequent self-assembly into Gd-nanoparticles (GdNPs). This results in enhancedr1relaxivity-19.0 (post-activation) vs. 10.2 mM-1s-1(pre-activation) at 1 T in solution-and prolonged accumulation in chemotherapy-induced apoptotic cells and tumors that express active caspase-3/7. We demonstrate that C-SNAM reports caspase-3/7 activity by generating a significantly brighterT1-weighted MR signal compared to non-treated tumors following intravenous administration of C-SNAM, providing great potential for high-resolution imaging of tumor apoptosisin vivo.
authors.affiliation: Molecular Imaging Program at Stanford, Stanford University, 1201 Welch Road, Stanford, California 94305-5484, USA.
authors.forename: Deju
authors.initials: D
authors.lastname: Ye
authors.affiliation: Molecular Imaging Program at Stanford, Stanford University, 1201 Welch Road, Stanford, California 94305-5484, USA.
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Shuhendler
authors.affiliation: Molecular Imaging Program at Stanford, Stanford University, 1201 Welch Road, Stanford, California 94305-5484, USA.
authors.forename: Prachi
authors.initials: P
authors.lastname: Pandit
authors.affiliation: Molecular Imaging Program at Stanford, Stanford University, 1201 Welch Road, Stanford, California 94305-5484, USA.
authors.forename: Kimberly D
authors.initials: KD
authors.lastname: Brewer
authors.affiliation: Molecular Imaging Program at Stanford, Stanford University, 1201 Welch Road, Stanford, California 94305-5484, USA.
authors.forename: Sui Seng
authors.initials: SS
authors.lastname: Tee
authors.affiliation: Molecular Imaging Program at Stanford, Stanford University, 1201 Welch Road, Stanford, California 94305-5484, USA.
authors.forename: Lina
authors.initials: L
authors.lastname: Cui
authors.affiliation: Molecular Imaging Program at Stanford, Stanford University, 1201 Welch Road, Stanford, California 94305-5484, USA.
authors.forename: Grigory
authors.initials: G
authors.lastname: Tikhomirov
authors.affiliation: Molecular Imaging Program at Stanford, Stanford University, 1201 Welch Road, Stanford, California 94305-5484, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Rutt
authors.affiliation: Molecular Imaging Program at Stanford, Stanford University, 1201 Welch Road, Stanford, California 94305-5484, USA ; Departments of Radiology Chemistry, Stanford University, 1201 Welch Road, Stanford, California 94305-5484, USA.
authors.forename: Jianghong
authors.initials: J
authors.lastname: Rao