Radiolabeled RGD Tracer Kinetics Annotates Differential [alpha]^sub v^[beta]^sub 3^ Integrin Expression Linked to Cell Intrinsic and Vessel Expression

• Published in: Molecular imaging and biology Vol. 16; no. 4; p. 558
• Main Authors: Alam, Israt S, Witney, Timothy H, Tomasi, Giampaolo, Carroll, Laurence, Twyman, Frazer J, Nguyen, Quang-dé, Aboagye, Eric O
• Format: Journal Article
• Language: English
• Published: New York Springer Nature B.V 01.08.2014
• ISSN: 1536-1632; 1860-2002
• DOI: 10.1007/s11307-013-0710-3

The purpose of this paper is to study the association between RGD binding kinetics and [alpha]^sub v^[beta]^sub 3^ integrin receptor density in the complex tumor milieu. We assessed [alpha]^sub v^[beta]^sub 3^ in vitro and by ^sup 68^Ga-DOTA-[c(RGDfK)]^sub 2^ positron emission tomography (PET) in tumors with varying [alpha]^sub v^[beta]^sub 3^. Intrinsic [alpha]^sub v^[beta]^sub 3^ expression decreased in the order of M21>>>MDA-MB-231>M21L in cells. Tumor volume of distribution by PET, V ^sub 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 [alpha]^sub v^[beta]^sub 3^. V ^sub T^ for MDA-MB-231 (0.40±0.04) was comparable to M21 despite lower [alpha]^sub v^[beta]^sub 3^ 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 [alpha]^sub v^[beta]^sub 3^ integrin expression--a key component of the angiogenesis phenotype--in vivo.[PUBLICATION ABSTRACT]