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 Kraitchman, Ricardo Rodriguez, Jeff W 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 1 2015

Fingerprint

Fluorine
Blood Vessels
Clinical Protocols
Treatment Failure
Adipose Tissue
Cell Survival
Flow Cytometry

Keywords

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

ASJC Scopus subject areas

  • Cell Biology
  • Developmental Biology

Cite this

Rose, L. C., Kadayakkara, D. K., Wang, G., Bar-Shir, A., Helfer, B. M., O’Hanlon, C. F., ... Bulte, J. W. (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

Fluorine-19 labeling of stromal vascular fraction cells for clinical imaging applications. / Rose, Laura C.; Kadayakkara, Deepak K.; Wang, Guan; Bar-Shir, Amnon; Helfer, Brooke M.; O’Hanlon, Charles F.; Kraitchman, Dara; Rodriguez, Ricardo; Bulte, Jeff W.

In: Stem cells translational medicine, Vol. 4, No. 12, 01.12.2015, p. 1472-1481.

Research output: Contribution to journalArticle

Rose, LC, Kadayakkara, DK, Wang, G, Bar-Shir, A, Helfer, BM, O’Hanlon, CF, Kraitchman, D, Rodriguez, R & Bulte, JW 2015, 'Fluorine-19 labeling of stromal vascular fraction cells for clinical imaging applications', Stem cells translational medicine, vol. 4, no. 12, pp. 1472-1481. https://doi.org/10.5966/sctm.2015-0113
Rose LC, Kadayakkara DK, Wang G, Bar-Shir A, Helfer BM, O’Hanlon CF et al. Fluorine-19 labeling of stromal vascular fraction cells for clinical imaging applications. Stem cells translational medicine. 2015 Dec 1;4(12):1472-1481. https://doi.org/10.5966/sctm.2015-0113
Rose, Laura C. ; Kadayakkara, Deepak K. ; Wang, Guan ; Bar-Shir, Amnon ; Helfer, Brooke M. ; O’Hanlon, Charles F. ; Kraitchman, Dara ; Rodriguez, Ricardo ; Bulte, Jeff W. / Fluorine-19 labeling of stromal vascular fraction cells for clinical imaging applications. In: Stem cells translational medicine. 2015 ; Vol. 4, No. 12. pp. 1472-1481.
@article{d2ce699c898f404ea4808ff3b5aed448,
title = "Fluorine-19 labeling of stromal vascular fraction cells for clinical imaging applications",
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.",
keywords = "Breast cancer, Cell tracking, Fluorine, Liposuction, Magnetic resonance imaging, Radiation-induced fibrosis, Stromal vascular fraction",
author = "Rose, {Laura C.} and Kadayakkara, {Deepak K.} and Guan Wang and Amnon Bar-Shir and Helfer, {Brooke M.} and O’Hanlon, {Charles F.} and Dara Kraitchman and Ricardo Rodriguez and Bulte, {Jeff W}",
year = "2015",
month = "12",
day = "1",
doi = "10.5966/sctm.2015-0113",
language = "English (US)",
volume = "4",
pages = "1472--1481",
journal = "Stem cells translational medicine",
issn = "2157-6564",
publisher = "AlphaMed Press",
number = "12",

}

TY - JOUR

T1 - Fluorine-19 labeling of stromal vascular fraction cells for clinical imaging applications

AU - Rose, Laura C.

AU - Kadayakkara, Deepak K.

AU - Wang, Guan

AU - Bar-Shir, Amnon

AU - Helfer, Brooke M.

AU - O’Hanlon, Charles F.

AU - Kraitchman, Dara

AU - Rodriguez, Ricardo

AU - Bulte, Jeff W

PY - 2015/12/1

Y1 - 2015/12/1

N2 - 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.

AB - 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.

KW - Breast cancer

KW - Cell tracking

KW - Fluorine

KW - Liposuction

KW - Magnetic resonance imaging

KW - Radiation-induced fibrosis

KW - Stromal vascular fraction

UR - http://www.scopus.com/inward/record.url?scp=84949665397&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84949665397&partnerID=8YFLogxK

U2 - 10.5966/sctm.2015-0113

DO - 10.5966/sctm.2015-0113

M3 - Article

C2 - 26511652

AN - SCOPUS:84949665397

VL - 4

SP - 1472

EP - 1481

JO - Stem cells translational medicine

JF - Stem cells translational medicine

SN - 2157-6564

IS - 12

ER -