Fluorine-19 labeling of stromal vascular fraction cells for clinical imaging applications

Laura C. Rose, Deepak K. Kadayakkara, Guan Wang, Amnon Bar-Shir, Brooke M. Helfer, Charles F. O’Hanlon, Dara L. Kraitchman, Ricardo L. Rodriguez, Jeff W.M. Bulte

Research output: Contribution to journalArticle

Abstract

Stromal vascular fraction (SVF) cells are used clinically for various therapeutic targets. The location and persistence of engrafted SVF cells are important parameters for determining treatment failure versus success. We used the GID SVF-1 platform and a clinical protocol to harvest and label SVF cells with the fluorinated (19F) agent CS-1000 as part of a first-in-human phase I trial (clinicaltrials.gov identifier NCT02035085) to track SVF cells with magnetic resonance imaging during treatment of radiationinduced fibrosis in breast cancer patients. Flow cytometry revealed that SVF cells consisted of 25.0%6 15.8% CD45+, 24.6%612.5% CD34+, and 7.5%63.3% CD31+ cells, with 2.160.73105 cells per cubic centimeter of adipose tissue obtained. Fluorescent CS-1000 (CS-ATM DM Green) labeled 87.0% 6 13.5% of CD34+ progenitor cells compared with 47.8% 6 18.5% of hematopoietic CD45+ cells, with an average of 2.8 6 2.0 3 1012 19F atoms per cell, determined using nuclear magnetic resonance spectroscopy. The vast majority (92.7%65.0%) of CD31+ cellswere also labeled, althoughmost coexpressed CD34.Only16%622.3%of CD452/CD312/CD342(triple-negative) cellswere labeledwith CS-ATMDM Green. After induction of cell death by either apoptosis or necrosis, >95% of19F was released from the cells, indicating that fluorine retention can be used as a surrogate marker for cell survival. Labeled-SVF cells engrafted in a siliconebreastphantomcould be visualizedwith a clinical 3-Teslamagnetic resonance imaging scanner at a sensitivity of approximately 23106 cells at a depth of 5 mm. The current protocol can be used to image transplanted SVF cells at clinically relevant cell concentrations in patients.

Original languageEnglish (US)
Pages (from-to)1472-1481
Number of pages10
JournalStem Cells Translational Medicine
Volume4
Issue number12
DOIs
StatePublished - Dec 2015

Keywords

  • Breast cancer
  • Cell tracking
  • Fluorine
  • Liposuction
  • Magnetic resonance imaging
  • Radiation-induced fibrosis
  • Stromal vascular fraction

ASJC Scopus subject areas

  • Developmental Biology
  • Cell Biology

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    Rose, L. C., Kadayakkara, D. K., Wang, G., Bar-Shir, A., Helfer, B. M., O’Hanlon, C. F., Kraitchman, D. L., Rodriguez, R. L., & Bulte, J. W. M. (2015). Fluorine-19 labeling of stromal vascular fraction cells for clinical imaging applications. Stem Cells Translational Medicine, 4(12), 1472-1481. https://doi.org/10.5966/sctm.2015-0113