Radiolabeled RGD tracer kinetics annotates differential αvβ3 integrin expression linked to cell intrinsic and vessel expression

TY - JOUR

T1 - Radiolabeled RGD tracer kinetics annotates differential αvβ3 integrin expression linked to cell intrinsic and vessel expression

AU - Alam, I.S.

AU - Witney, Timothy H.

AU - Tomasi, G.

AU - Carroll, L.

AU - Twyman, F.J.

AU - Nguyen, Q.-D.

AU - Aboagye, E.O.

N1 - Export Date: 14 November 2018

PY - 2014/8

Y1 - 2014/8

N2 - 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. © 2013 World Molecular Imaging Society.

AB - 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. © 2013 World Molecular Imaging Society.

U2 - 10.1007/s11307-013-0710-3

DO - 10.1007/s11307-013-0710-3

M3 - Article

SN - 1536-1632

VL - 16

SP - 558

EP - 566

JO - MOLECULAR IMAGING AND BIOLOGY

JF - MOLECULAR IMAGING AND BIOLOGY

IS - 4

ER -