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. Aboagye

Research output: Contribution to journalArticlepeer-review

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 α vβ3 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 αvβ 3. VT 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.

Original languageEnglish (US)
Pages (from-to)558-566
Number of pages9
JournalMolecular Imaging and Biology
Volume16
Issue number4
DOIs
StatePublished - Aug 2014
Externally publishedYes

Keywords

  • Integrin
  • Kinetic modeling
  • Positron emission tomography
  • RGD peptide
  • Vasculature

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

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