CTSS and neoplasm: As a starting point for thisstudy, we chose a previously published quenched pan-cathepsin substrate 6QC, containing sulfo-Cy5 as the fluorophore and sulfo-QSY21as the quencher (Figure 1b).24 Cathepsin-targeted probes have provento be valuable tools for tumor imaging12,13,25−27 and 6QC, in particular,has been optimized for this application.24,28,29 We designed analogues of 6QC that introduce a spacer and a terminal amino group that can be usedfor incorporation onto the pHPMA precursor (Figure 1d,f,h).