Radiolabeled RGD Tracer Kinetics Annotates Differential αvβ3 Integrin Expression Linked to Cell Intrinsic and Vessel Expression
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- Alam, I.S., Witney, T.H., Tomasi, G. et al. Mol Imaging Biol (2014) 16: 558. doi:10.1007/s11307-013-0710-3
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The purpose of this paper is to study the association between RGD binding kinetics and αvβ3 integrin receptor density in the complex tumor milieu.
We assessed αvβ3in vitro and by 68Ga-DOTA-[c(RGDfK)]2 positron emission tomography (PET) in tumors with varying αvβ3.
Intrinsic αvβ3 expression decreased in the order of M21 >>> MDA-MB-231 > M21L in cells. Tumor volume of distribution by PET, VT, 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. 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.
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.