In this study, we employ TAK-164, a guanylyl-cyclase C (GCC)-targeted ADC currently under clinical evaluation for colorectal cancer and GI malignancy indications carrying DGN549, a potent DNA-alkylating payload with reported bystander effects [14], to pharmacodynamically map bystander payload tissue penetration. The gene discussed is GUCY2C; the disease is colorectal cancer.