title: Necrosis targeted combinational theragnostic approach using radioiodinated Sennidin A in rodent tumor models.
abstract: 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.
authors.affiliation: Laboratory of Translational Medicine, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing 210028, Jiangsu Province, P.R.China;Department of Natural Medicinal Chemistry and State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, Jiangsu Province, P.R.China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Ji
authors.forename: Cuihua
authors.initials: C
authors.lastname: Jiang
authors.forename: Xueli
authors.initials: X
authors.lastname: Zhang
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.forename: Meng
authors.initials: M
authors.lastname: Gao
authors.forename: Yue
authors.initials: Y
authors.lastname: Li
authors.forename: Junhu
authors.initials: J
authors.lastname: Wang
authors.forename: Qingqing
authors.initials: Q
authors.lastname: Wang
authors.forename: Ziping
authors.initials: Z
authors.lastname: Sun
authors.forename: Xiao
authors.initials: X
authors.lastname: Jiang
authors.forename: Nan
authors.initials: N
authors.lastname: Yao
authors.forename: Xiaoning
authors.initials: X
authors.lastname: Wang
authors.forename: Zhijun
authors.initials: Z
authors.lastname: Fang
authors.forename: Zhiqi
authors.initials: Z
authors.lastname: Yin
authors.forename: Yicheng
authors.initials: Y
authors.lastname: Ni
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000873:Anthracenes / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D001345:Autoradiography; D004195:Disease Models, Animal; D007457:Iodine Radioisotopes / Q000008:administration & dosage*; D008279:Magnetic Resonance Imaging; D051379:Mice; D009336:Necrosis / Q000139:chemically induced / Q000473:pathology; D009374:Neoplasms, Experimental / Q000188:drug therapy*; D049268:Positron-Emission Tomography; D051381:Rats; D017207:Rats, Sprague-Dawley; D013267:Stilbenes / Q000008:administration & dosage*
chemical_list: D000873:Anthracenes; D007457:Iodine Radioisotopes; D013267:Stilbenes; C013946:dihydroxydianthrone; C058728:fosbretabulin