title: Molecular Magnetic Resonance Imaging of Tumor Response to Therapy.
abstract: Personalized cancer medicine requires measurement of therapeutic efficacy as early as possible, which is optimally achieved by three-dimensional imaging given the heterogeneity of cancer. Magnetic resonance imaging (MRI) can obtain images of both anatomy and cellular responses, if acquired with a molecular imaging contrast agent. The poor sensitivity of MRI has limited the development of activatable molecular MR contrast agents. To overcome this limitation of molecular MRI, a novel implementation of our caspase-3-sensitive nanoaggregation MRI (C-SNAM) contrast agent is reported. C-SNAM is triggered to self-assemble into nanoparticles in apoptotic tumor cells, and effectively amplifies molecular level changes through nanoaggregation, enhancing tissue retention and spin-lattice relaxivity. At one-tenth the current clinical dose of contrast agent, and following a single imaging session, C-SNAM MRI accurately measured the response of tumors to either metronomic chemotherapy or radiation therapy, where the degree of signal enhancement is prognostic of long-term therapeutic efficacy. Importantly, C-SNAM is inert to immune activation, permitting radiation therapy monitoring.
authors.affiliation: Molecular Imaging Program at Stanford, Stanford, California 94305, USA.|Departments of Radiology, Stanford, California 94305, USA.
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Shuhendler
authors.affiliation: Molecular Imaging Program at Stanford, Stanford, California 94305, USA.|Departments of Radiology, Stanford, California 94305, USA.
authors.forename: Deju
authors.initials: D
authors.lastname: Ye
authors.affiliation: Molecular Imaging Program at Stanford, Stanford, California 94305, USA.|Departments of Radiology, Stanford, California 94305, USA.
authors.forename: Kimberly D
authors.initials: KD
authors.lastname: Brewer
authors.affiliation: Molecular Imaging Program at Stanford, Stanford, California 94305, USA.|Radiation Oncology, Stanford, California 94305, USA.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Bazalova-Carter
authors.affiliation: Molecular Imaging Program at Stanford, Stanford, California 94305, USA.|Departments of Radiology, Stanford, California 94305, USA.
authors.forename: Kyung-Hyun
authors.initials: KH
authors.lastname: Lee
authors.affiliation: Materials Science and Engineering, Stanford University, Stanford, California 94305, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Kempen
authors.affiliation: Department of Chemical Engineering, Department of Biological Engineering, and Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, 02139, USA.
authors.forename: K
authors.initials: K
authors.lastname: Dane Wittrup
authors.affiliation: Molecular Imaging Program at Stanford, Stanford, California 94305, USA.|Radiation Oncology, Stanford, California 94305, USA.
authors.forename: Edward E
authors.initials: EE
authors.lastname: Graves
authors.affiliation: Molecular Imaging Program at Stanford, Stanford, California 94305, USA.|Departments of Radiology, Stanford, California 94305, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Rutt
authors.affiliation: Molecular Imaging Program at Stanford, Stanford, California 94305, USA.|Departments of Radiology, Stanford, California 94305, USA.
authors.forename: Jianghong
authors.initials: J
authors.lastname: Rao
mesh_terms: D059250:Administration, Metronomic; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage; D053148:Caspase 3 / Q000378:metabolism; D003287:Contrast Media / Q000737:chemistry; D003545:Cysteine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000737:chemistry; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D006367:HeLa Cells; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008819:Mice, Nude; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology* / Q000532:radiotherapy; D011804:Quinolines / Q000008:administration & dosage / Q000737:chemistry; D016896:Treatment Outcome; D023041:Xenograft Model Antitumor Assays / Q000379:methods
chemical_list: D000903:Antibiotics, Antineoplastic; C000612149:C-SNAM compound; D003287:Contrast Media; D011804:Quinolines; D004317:Doxorubicin; D053148:Caspase 3; D003545:Cysteine