Optical imaging of progenitor cell homing to patient-derived tumors

Isabel G. Newton, Warren C. Plaisted, Steven Messina-Graham, Annelie E. Abrahamsson Schairer, Alice Y. Shih, Evan Y. Snyder, Catriona H M Jamieson, Robert F. Mattrey

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

Capitalizing on cellular homing to cancer is a promising strategy for targeting malignant cells for diagnostic, monitoring and therapeutic purposes. Murine C17.2 neural progenitor cells (NPC) demonstrate a tropism for cell line-derived tumors, but their affinity for patient-derived tumors is unknown. We tested the hypothesis that NPC accumulate in patient-derived tumors at levels detectable by optical imaging. Mice bearing solid tumors after transplantation with patient-derived leukemia cells and untransplanted controls received 106 fluorescent DiR-labeled NPC daily for 1-4 days, were imaged, then sacrificed. Tissues were analyzed by immunofluorescence and flow cytometry to detect tumor cell engraftment (CD45) and NPC (FITC-β galactosidase or DiR). Tumors consisted primarily of CD45-positive cells and demonstrated mild fluorescence, corresponding to frequent clusters of FITC-β gal-positive cells. Both transplanted and control mice demonstrated the highest fluorescent signal in the spleens and other tissues of the reticuloendothelial activating system. However, only rare FITC-β gal-positive cells were detected in the mildly engrafted transplanted spleens and none in the control spleens, suggesting that their high DiR signal reflects the sequestration of DiR-positive debris. The mildly engrafted transplanted kidneys demonstrated low fluorescent signal and rare FITC-β gal-positive cells whereas control kidneys were negative. Results indicate that NPC accumulate in tissues containing patient-derived tumor cells in a manner that is detectable by ex vivo optical imaging and proportional to the level of tumor engraftment, suggesting a capacity to home to micrometastatic disease. As such, NPC could have significant clinical applications for the targeted diagnosis and treatment of cancer.

Original languageEnglish (US)
Pages (from-to)525-536
Number of pages12
JournalContrast Media and Molecular Imaging
Volume7
Issue number6
DOIs
StatePublished - Nov 1 2012

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Keywords

  • C17.2
  • Cellular imaging
  • Chronic myeloid leukemia
  • FACS
  • Fluorescent probes
  • Homing
  • Humanized cancer model
  • Immunofluorescence
  • Neural progenitor cells

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

Cite this

Newton, I. G., Plaisted, W. C., Messina-Graham, S., Abrahamsson Schairer, A. E., Shih, A. Y., Snyder, E. Y., Jamieson, C. H. M., & Mattrey, R. F. (2012). Optical imaging of progenitor cell homing to patient-derived tumors. Contrast Media and Molecular Imaging, 7(6), 525-536. https://doi.org/10.1002/cmmi.1485