Advances in metal-DOTA/DTPA complexes for mass cytometry

Mass cytometry, a cutting-edge single-cell analytical technique, has achieved high-resolution, high-throughput, and simultaneous detection of multiple parameters. This technique fundamentally differs from conventional flow cytometry by employing stable isotope (primarily lanthanide) tags instead of fluorophores, thereby overcoming spectral limitations. Among the diverse mass tag reagents developed to date, metal-chelated complexes using bifunctional chelators, particularly 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) and diethylenetriaminepentaacetic acid (DTPA), have been widely used due to their exceptional thermodynamic stability, kinetic inertness under physiological conditions, and versatile conjugation chemistry. This review summarizes the working mechanisms of mass tag reagents and the design of metal-DOTA/DTPA complexes. Additionally, we classify these compounds into DOTA/DTPA-based metal-chelating polymers, DOTA/DTPA-based polymer microbeads, and DOTA/DTPA-based small molecules and present an in-depth exploration of metal-DOTA/DTPA complexes in mass cytometry applications.