title: Minimally invasive in tumor multidrug comparative analysis with contrast-enhanced MRI in mice.
abstract: To facilitate decision making in the oncology clinic, technologies have recently been developed to independently inject and assess multiple anticancer agents directly in a patient's tumor. To increase the flexibility of this approach beyond histological readouts of response, contrast-enhanced MRI was evaluated for the detection of cell death in living tumors after injection.
  
  
  
  A six-needle arrayed microinjection device designed to provide head-to-head comparisons of chemotherapy responses in living tumors was used. Xenografted non-Hodgkin lymphoma tumors in athymic Nude-Foxn1(nu) mice were injected either with different doses of vincristine or with one needle each of vincristine, doxorubicin, bendamustine, prednisolone, mafosfamide, and a vehicle control. To assess drug responses, measurements of enhancement by T1-weighted contrast-enhanced MRI were made for individual sites at 24, 48, and 72 h after injection. For comparison, histological evaluations of cell death were obtained after tumor resection.
  
  
  
  Measurements of MRI enhancement at injection sites showed a significant (P < 0.001) positive regression slope as a function of vincristine dose. Average MRI measurements were closely correlated with cell death by hematoxylin and eosin staining (R = 0.81; P = 0.001).
  
  
  
  Contrast-enhanced MRI has the potential to replace or augment histological analyses of tumor responses to microinjected doses of chemotherapy agents with potential application in selecting optimal chemotherapy regimens. Magn Reson Med 76:946-952, 2016. © 2015 Wiley Periodicals, Inc.
authors.affiliation: Presage Biosciences, Inc., Seattle, Washington, USA.
authors.forename: William S
authors.initials: WS
authors.lastname: Kerwin
authors.affiliation: Presage Biosciences, Inc., Seattle, Washington, USA.
authors.forename: Ilona
authors.initials: I
authors.lastname: Tretyak
authors.affiliation: Presage Biosciences, Inc., Seattle, Washington, USA.
authors.forename: Marc O
authors.initials: MO
authors.lastname: Grenley
authors.affiliation: Presage Biosciences, Inc., Seattle, Washington, USA.
authors.forename: Sheng
authors.initials: S
authors.lastname: You
authors.affiliation: Presage Biosciences, Inc., Seattle, Washington, USA.
authors.forename: Beryl A
authors.initials: BA
authors.lastname: Hatton
authors.affiliation: Presage Biosciences, Inc., Seattle, Washington, USA.
authors.forename: Alicia
authors.initials: A
authors.lastname: Moreno-Gonzalez
authors.affiliation: Presage Biosciences, Inc., Seattle, Washington, USA.
authors.forename: Derek J
authors.initials: DJ
authors.lastname: Thirstrup
authors.affiliation: Presage Biosciences, Inc., Seattle, Washington, USA.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Klinghoffer
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D016903:Drug Monitoring / Q000379:methods*; D008228:Lymphoma, Non-Hodgkin / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000473:pathology; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D008819:Mice, Nude; D008845:Microinjections / Q000379:methods*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D016896:Treatment Outcome
keywords: MRI; arrayed microinjection; chemotherapy; contrast enhancement; lymphoma