Residual cancer cells and subsequent
tumor relapse is an obstacle for curative
cancer treatment.
Tumor necrosis therapy (
TNT) has recently been developed to cause
residual tumor regression or destruction. Here, we exploited the avidity of the
sennidin A (SA) tracer and radioiodinated SA (¹³¹I-SA) to necrotic
tumors in order to further empower
TNT. We showed high uptake and prolonged retention of SA in necrotic
tumors and a quick clearance in other non-targeted tissues including the liver. On SPECT-CT images,
tumor mass appeared persistently as a hotspot. Based on the prominent targetability of ¹³¹I-SA to the
tumor necrosis, we designed a combinational theragnostic modality. The vascular disrupting agent (VDA)
combretastatin A4 phosphate (CA4P) was used to cause massive
tumor necrosis, which formed the target of ¹³¹I-SA that subsequently killed the
residual tumor cells by cross-fire irradiation of beta particles. Consequently, ¹³¹I-SA combined with CA4P significantly inhibited
tumor growth, extended
tumor doubling time and prolonged mean animal survival. In conclusion, ¹³¹I-SA in combination with
necrosis inducing drugs/
therapies may generate synergetic tumoricidal effects on solid
malignancies by means of primary debulking and secondary cleansing process.