A dose- and time-controllable syngeneic animal model of breast cancer microcalcification

Fangbing Liu, Preeti Misra, Elaine P. Lunsford, Joanne T. Vannah, Yuxia Liu, Robert E. Lenkinski, John V. Frangioni

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

The development of novel diagnostic agents for the detection of breast cancer microcalcifications requires a reliable animal model. Based on previous work from our group, we hypothesized that a single systemic injection of recombinant bone morphogenetic protein-2 (rBMP-2) could be used to create such a model. The cDNA encoding mature human BMP-2 was expressed in BL21(DE3) bacteria, purified to homogeneity, and refolded as a dimer. Bioactivity was confirmed using a C2C12 alkaline phosphatase assay. rBMP-2 was radiolabeled with 99mTc, and its biodistribution and clearance were quantified after both intravenous (IV) and intraperitoneal (IP) injection. Fischer 344 rats bearing syngeneic R3230 breast tumors received a single intraperitoneal injection of rBMP-2 at a specified dose. Tumor microcalcification was quantified over time using micro-single photon emission computed tomography (SPECT) and microcomputed tomography (CT). rBMP-2 could be expressed in E. coli at high levels, isolated at >95% purity, and refolded to a bioactive dimer. Beta-phase half-life was 30.5 min after IV administration and 47.6 min after IP administration. Renal excretion was the primary mode of clearance. A single IP injection of ≥50 μg rBMP-2 when tumors were not yet palpable resulted in dose-dependent microcalcification in 8 of 8 R3230 tumors. No calcification was found in control tumors or in normal tissues and organs of animals injected with rBMP-2. Tumor calcification increased progressively between weeks 2 and 4 post-rBMP-2 injection. A single IP injection of rBMP-2 in rats bearing a syngeneic breast cancer will produce dose-dependent and time-dependent microcalcifications. This animal model lays the foundation for the development of novel diagnostic radiotracers for breast cancer.

Original languageEnglish (US)
Pages (from-to)87-94
Number of pages8
JournalBreast Cancer Research and Treatment
Volume122
Issue number1
DOIs
StatePublished - Jul 1 2010

Keywords

  • Animal models
  • BMP-2
  • Breast cancer
  • Micro-CT
  • Micro-SPECT/CT
  • Microcalcifications

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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  • Cite this

    Liu, F., Misra, P., Lunsford, E. P., Vannah, J. T., Liu, Y., Lenkinski, R. E., & Frangioni, J. V. (2010). A dose- and time-controllable syngeneic animal model of breast cancer microcalcification. Breast Cancer Research and Treatment, 122(1), 87-94. https://doi.org/10.1007/s10549-009-0535-6