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Molecular Imaging and Biology

, Volume 16, Issue 4, pp 558–566 | Cite as

Radiolabeled RGD Tracer Kinetics Annotates Differential αvβ3 Integrin Expression Linked to Cell Intrinsic and Vessel Expression

  • Israt S. Alam
  • Timothy H. Witney
  • Giampaolo Tomasi
  • Laurence Carroll
  • Frazer J. Twyman
  • Quang-Dé Nguyen
  • Eric O. AboagyeEmail author
Research Article

Abstract

Purpose

The purpose of this paper is to study the association between RGD binding kinetics and αvβ3 integrin receptor density in the complex tumor milieu.

Procedures

We assessed αvβ3 in vitro and by 68Ga-DOTA-[c(RGDfK)]2 positron emission tomography (PET) in tumors with varying αvβ3.

Results

Intrinsic αvβ3 expression decreased in the order of M21 >>> MDA-MB-231 > M21L in cells. Tumor volume of distribution by PET, V T, was significantly higher in M21 compared to isogenic M21L tumors (0.40 ± 0.01 versus 0.25 ± 0.02; p < 0.01) despite similar microvessel density (MVD) likely due to higher αvβ3. V T for MDA-MB-231 (0.40 ± 0.04) was comparable to M21 despite lower αvβ3 but in keeping with the higher MVD, suggesting superior tracer distribution.

Conclusions

This study demonstrates that radioligand binding kinetics of PET data can be used to discriminate tumors with different αvβ3 integrin expression—a key component of the angiogenesis phenotype—in vivo.

Key words

Integrin RGD peptide Positron emission tomography Kinetic modeling Vasculature 

Notes

Acknowledgments

This work was funded by Cancer Research UK-Engineering and Physical Sciences Research Council grant C2536/A10337. E.O.A’s laboratory receives core funding from the UK Medical Research Council (MC US A652 0030).

Conflict of Interest

The authors declare no conflicts of interest.

Supplementary material

11307_2013_710_MOESM1_ESM.docx (2.1 mb)
ESM 1 (DOCX 2.05 mb)

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Copyright information

© World Molecular Imaging Society 2013

Authors and Affiliations

  • Israt S. Alam
    • 1
  • Timothy H. Witney
    • 1
  • Giampaolo Tomasi
    • 1
  • Laurence Carroll
    • 1
  • Frazer J. Twyman
    • 1
  • Quang-Dé Nguyen
    • 1
  • Eric O. Aboagye
    • 1
    Email author
  1. 1.Comprehensive Cancer Imaging Centre, Faculty of MedicineImperial College LondonLondonUK

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