Radiolabeled RGD tracer kinetics annotates differential α_vβ₃ integrin expression linked to cell intrinsic and vessel expression

Purpose: The purpose of this paper is to study the association between RGD binding kinetics and α_vβ₃ integrin receptor density in the complex tumor milieu. Procedures: We assessed α_vβ₃ in vitro and by ⁶⁸Ga-DOTA- [c(RGDfK)]₂ positron emission tomography (PET) in tumors with varying α_vβ₃. 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 α_vβ ₃. V_T for MDA-MB-231 (0.40±0.04) was comparable to M21 despite lower α_vβ₃ 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 α_vβ₃ integrin expression-a key component of the angiogenesis phenotype - in vivo.