Synthesis and Preliminary Evaluation of ⁶⁸Ga‐NOTA‐Biphenyl‐c(RGDyK) for the Quantification of Integrin α_vβ₃

Abstract

Arginine‐glycine‐aspartate (RGD) peptide binds to the integrin αvβ3, which plays a crucial role in tumor angiogenesis and metastasis. Previously developed 68Ga‐labeled cyclic RGD peptides are rapidly excreted from the circulatory system. In the present study, we developed a 68Ga‐labeled cyclic RGD peptide with a biphenyl group between the chelator and RGD peptide, i.e., 68Ga‐NOTA‐biphenyl‐c(RGDyK). Then, we performed the comparison with the reference compound, i.e., 68Ga‐NOTA‐c(RGDyK). 68Ga‐NOTA‐biphenyl‐c(RGDyK) was 37% less hydrophilic than 68Ga‐NOTA‐c(RGDyK). For positron emission tomography imaging, 68Ga‐NOTA‐biphenyl‐c(RGDyK) had a longer retention time and showed a higher signal‐to‐noise ratio in tumors than 68Ga‐NOTA‐c(RGDyK). However, the biphenyl‐radiopeptide displayed the relatively high non‐specific binding. From these perspectives, incorporation of the biphenyl group to the RGD generates pros and cons.