RT01: A novel anti-TF, radionuclide drug conjugate (RDC) for theranostic precision oncology

Tissue Factor (TF) is an attractive therapeutic target for various tumors. We developed RT01, a first-in-class, targeted radio-theranostic agent consisting of a humanized anti-TF antibody conjugated to the diagnostic 89 Zr or therapeutic 177 Lu radionuclide. In a xenograft tumor model, SPECT/CT imaging demonstrated rapid and specific tumor accumulation of RT01-177 Lu (single 200μCi i.v. dose), with retention over 6 days and rapid non-target clearance (background decreased by 4 hours post-injection). The tumor-to-kidney ratio of radiation intensity uptake (%ID/cc) exceeded 9.2. This single 200μCi dose injection of RT01-177 Lu demonstrated potent anti-tumor efficacy and excellent tolerability. Histopathology analysis of ten major organs (kidney, intestine, brain, lung, liver, femur, spleen, stomach, heart, and pancreas) revealed no observable abnormalities or serious toxicity. In conclusion, the RT01 theranostic pair provides superior tumor targeting, rapid non-target clearance, and a favorable toxicity profile, supporting its continued clinical development for TF-positive cancers.