<sup>99m</sup>Tc-Labeled Cyclic RGDfK Dimer:  Initial Evaluation for SPECT Imaging of Glioma Integrin α<sub>v</sub>β<sub>3</sub> Expression

This report describes the evaluation of biodistribution properties of three radiotracers, [<sup>99m</sup>Tc(SQ168)(EDDA)], [<sup>99m</sup>Tc(SQ168)(tricine)(PDA)], and [<sup>99m</sup>Tc(SQ168)(tricine)(TPPTS)] (SQ168 = [2-[[[5-[carboonyl]-2-pyridinyl]hydrazono]methyl]benzenesulfonic acid]-Glu(cyclo{Lys-Arg-Gly-Asp-d-Phe})-cyclo{Lys-Arg-Gly-Asp-d-Phe}; EDDA = ethylenediamine-<i>N</i>,<i>N</i>‘-diacetic acid; PDA = 2,5-pyridinedicarboxylic acid; TPPTS = trisodium triphenylphosphine-3,3‘,3‘ ‘-trisulfonate), and their potential to image the glioma integrin α<sub>v</sub>β<sub>3</sub> expression in BALB/c nude mice bearing the U87MG human glioma xenografts. It was found that all three radiotracers were able to localize in glioma tumors with a relatively high tumor uptake and long tumor retention time by binding to the integrin α<sub>v</sub>β<sub>3</sub> expressed on both tumor cells and endothelial cells of tumor neovasculature. It seems that the coligand has minimal effect on integrin α<sub>v</sub>β<sub>3</sub> targeting capability of the <sup>99m</sup>Tc-labeled RGDfK dimer, but it has a significant impact on their biodistribution properties. For example, the complex [<sup>99m</sup>Tc(SQ168)(tricine)(TPPTS)] has the lowest liver uptake and the highest metabolic stability in normal BALB/c nude mice. Results from SPECT imaging studies show that the glioma tumors can be clearly visualized with all three radiotracers at 4 h postinjection. Among the three radiotracers evaluated in this study, [<sup>99m</sup>Tc(SQ168)(tricine)(TPPTS)] has the best imaging quality and is a promising candidate for more preclinical evaluations in the future.