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

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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.

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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.

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Authors and Affiliations

  1. Comprehensive Cancer Imaging Centre, Faculty of Medicine, Imperial College London, London, W12 0NN, UK

    Israt S. Alam, Timothy H. Witney, Giampaolo Tomasi, Laurence Carroll, Frazer J. Twyman, Quang-Dé Nguyen & Eric O. Aboagye

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  1. Israt S. Alam
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  2. Timothy H. Witney
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  3. Giampaolo Tomasi
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  4. Laurence Carroll
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  5. Frazer J. Twyman
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  6. Quang-Dé Nguyen
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  7. Eric O. Aboagye
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Corresponding author

Correspondence to Eric O. Aboagye.

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Alam, I.S., Witney, T.H., Tomasi, G. et al. Radiolabeled RGD Tracer Kinetics Annotates Differential αvβ3 Integrin Expression Linked to Cell Intrinsic and Vessel Expression. Mol Imaging Biol 16, 558–566 (2014). https://doi.org/10.1007/s11307-013-0710-3

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  • DOI: https://doi.org/10.1007/s11307-013-0710-3

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