Cell-permeable [^99mTc(CO₃)]-labeled fluorogenic caspase 3 substrate for dual-modality detection of apoptosis

A study was conducted to demonstrate the formation of cell-permeable [ ^99mTc(CO₃)]-labeled fluorogenic caspase 3 substrate for dual-modality detection of apoptosis. The study focused on developing a single imaging probe that possessed both fluorescent and radioactive tags to allow optical and nuclear-imaging investigations. A number of significant criteria were considered for developing the probe. One of the criteria required the probe to be labeled with a radionuclide and a fluorogenic compound that activated upon cleavage from DEVD. The probe also needed to be cell permeable and needed to freely diffuse into and out of viable cells in its intact form. A murine lever apoptosis model was used to evaluate the potential of the chelate being used to image apoptosis in vivo. Quantitative analysis of the biodistribution of ^99mTc-chelate in anti-Fas-treated mice and PBS-treated mice was also performed using the cut-and-count method.