Folate receptor-targeted multimodality imaging of ovarian cancer in a novel syngeneic mouse model

Meltem Ocak, Andrea G. Gillman, Jamee Bresee, Lixin Zhang, Anda M. Vlad, Cristina Müller, Roger Schibli, W. Barry Edwards, Carolyn J. Anderson, H. Michael Gach

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

A new transplantable ovarian tumor model is presented using a novel folate receptor (FR) positive, murine ovarian cancer cell line that emulates the human disease and induces widespread intraperitoneal (i.p.) tumors in immunocompetent mice within 4-8 weeks of implantation. Tumor development was monitored using a new positron emission tomography (PET) FR-targeting reporter with PET/computerized tomography (PET/CT) and fluorescence molecular tomography (FMT) using a commercial FR-targeting reporter. Conventional structural magnetic resonance imaging (MRI) was also performed. Adult female C57BL/6 mice were injected i.p. with 6 × 106 MKP-L FR+ cells. Imaging was performed weekly beginning 2 weeks after tumor induction. The albumin-binding, FR-targeting ligand cm09 was radiolabeled with the positron emitter 68Ga and used to image the tumors with a small animal PET/CT. The FR-reporter FolateRSense 680 (PerkinElmer) was used for FMT and flow cytometry. Preclinical MRI (7 T) without FR-targeting was compared with the PET and FMT molecular imaging. Tumors were visible by all three imaging modalities. PET/CT had the highest imaging sensitivity at 3-3.5 h postadministration (mean %IA/g mean > 6) and visualized tumors earlier than the other two modalities with lower kidney uptake (mean %IA/g mean < 17) than previously reported FR-targeting agents in late stage disease. FMT showed relatively low FR-targeted agent in the bladder and kidneys, but yielded the lowest anatomical image resolution. MRI produced the highest resolution images, but it was difficult to distinguish tumors from abdominal organs during early progression since a FR-targeting MRI reporter was not used. Nevertheless, there was good correlation of imaging biomarkers between the three modalities. Tumors in the mouse ovarian cancer model could be detected using FR-targeted imaging as early as 2 weeks post i.p. injection of tumor cells. An imaging protocol should combine one or more of the modalities, e.g., PET/CT or PET/MRI for optimal tumor detection and delineation from surrounding tissues.

Original languageEnglish
Pages (from-to)542-553
Number of pages12
JournalMolecular Pharmaceutics
Volume12
Issue number2
DOIs
StatePublished - Feb 2 2015
Externally publishedYes

Keywords

  • FolateRSense
  • Ga
  • MRI
  • PET/CT
  • cm09
  • fluorescence molecular tomography
  • folate receptor targeting
  • immunocompetent ovarian cancer mouse model

Fingerprint Dive into the research topics of 'Folate receptor-targeted multimodality imaging of ovarian cancer in a novel syngeneic mouse model'. Together they form a unique fingerprint.

  • Cite this

    Ocak, M., Gillman, A. G., Bresee, J., Zhang, L., Vlad, A. M., Müller, C., Schibli, R., Edwards, W. B., Anderson, C. J., & Gach, H. M. (2015). Folate receptor-targeted multimodality imaging of ovarian cancer in a novel syngeneic mouse model. Molecular Pharmaceutics, 12(2), 542-553. https://doi.org/10.1021/mp500628g