CD133 has been recognized
as a prominent biomarker for cancer stem
cells (CSCs), which promote tumor relapse and metastasis. Here, we
developed a clinically relevant, stable, and peptide-based positron
emission tomography (PET) tracer, [64Cu]CM-2, for mapping
CD133 protein in several kinds of cancers. Through the incorporation
of a 6-aminohexanoic acid (Ahx) into the N terminus of a CM peptide,
we constructed a stable peptide tracer [64Cu]CM-2, which
exhibited specific binding to CD133-positive CSCs in multiple preclinical
tumor models. Both PET imaging and ex vivo biodistribution verified
the superb performance of [64Cu]CM-2. Furthermore, the
matched physical and biological half-life of [64Cu]CM-2
makes it a state-of-the-art PET tracer for CD133. Therefore, [64Cu]CM-2 PET may not only enable the longitudinal tracking
of CD133 dynamics in the cancer stem cell niche but also provide a
powerful and noninvasive imaging tool to track down CSCs in refractory
cancers.