For constructing a molecular imaging probe, tedious procedures are often needed for synthesis and purification. In this report, we demonstrated that pseudo-synthesis-free PET imaging is feasible via utilizing pro-ligand concept to design PET probes. In this proof-of-concept study, αvβ3 integrin in U87 tumors was imaged with a 64Cu-peptidic probe, in which linear peptide GHRGDHG is used as a pro-ligand (conceptually similar to pro-drug), while 64Cu bears three functional roles that include generation of PET signal, coordination with two GHs (Glycine-Histidine) moieties of the pro-ligand, and cyclizing the linear pro-ligand into an active cyclic-RGD form (termed as 64Cu-Cyclo-RGD) for αvβ3 integrin. Our pseudo-synthesis-free imaging method is different from “ready-to-use kit” PET imaging. Our design was inspired by the pro-drug concept, in which the linear peptidic pro-ligand is in its inactive form for αvβ3, thus it has no “cold compound” effect on occupancy of the imaging target. In vitro and in vivo data indicated that pseudo-synthesis-free PET imaging was feasible, as evidenced by 64Cu-Cyclo-RGD’s excellent specificity for αvβ3 integrin, fast clearance from the body, and high uptake in U87 tumors. We believe that our design strategy and pseudo-synthesis-free imaging concept could have a broad impact on designing of probes for other imaging targets.

Pseudo-synthesis-free PET imaging of αvβ3 integrin via its pro-ligand

256th National Meeting (2018)

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