title: Biodistribution and anti-tumor efficacy of intratumorally injected necrosis-avid theranostic agent radioiodinated hypericin in rodent tumor models.
abstract: Hypericin has an excellent necrosis-specific targeting capacity; thus, we explored small-molecular tumor necrosis therapy (SMTNT) for inhibiting tumor growth in rodent tumor models. H22 and S180 tumor-bearing Kunming (KM) mice were intratumorally injected with (131)I-monoiodohypericin ((131)I-MIH) to investigate the biodistribution of (131)I-MIH as a function of time. Single-photon emission computed tomography (SPECT), autoradiography, fluorescence microscopy and hematoxylin and eosin (H&E) staining were performed to determine the intra-tumoral distribution of (131)I-MIH. A therapeutic evaluation study was also performed in the tumor-bearing KM mice using saline and a positive drug as controls. Gamma counting, SPECT images, autoradiography and fluorescence microscopy and H&E staining results revealed intense retention of (131)I-MIH in the necrotic tumor over 168 h and good in vivo stability of the agent. Therapy with a single dose of intra-tumoral administration of (131)I-MIH caused significant tumor growth delay. A histopathological analysis of the tumors and normal organs further validated the therapeutic efficacy and limited systemic toxicity of (131)I-MIH. The prolonged tumor retention and effective therapy indicated that (131)I-MIH may be a promising intratumorally injected SMTNT agent.
authors.affiliation: Department of Nuclear Medicine, the First Affiliated Hospital of Nanjing Medical University , Nanjing, Jiangsu Province , China .
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.forename: Dongjian
authors.initials: D
authors.lastname: Zhang
authors.forename: Yuanbo
authors.initials: Y
authors.lastname: Feng
authors.forename: Yue
authors.initials: Y
authors.lastname: Li
authors.forename: Dejian
authors.initials: D
authors.lastname: Huang
authors.forename: Cuihua
authors.initials: C
authors.lastname: Jiang
authors.forename: Meng
authors.initials: M
authors.lastname: Gao
authors.forename: Fei
authors.initials: F
authors.lastname: Peng
authors.forename: Xiaoning
authors.initials: X
authors.lastname: Wang
authors.forename: Su
authors.initials: S
authors.lastname: Jing
authors.forename: Xiao
authors.initials: X
authors.lastname: Jiang
authors.forename: Yicheng
authors.initials: Y
authors.lastname: Ni
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000873:Anthracenes; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000633:toxicity; D001345:Autoradiography; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000473:pathology; D045744:Cell Line, Tumor; D015552:Injections, Intralesional; D007457:Iodine Radioisotopes / Q000737:chemistry; D008113:Liver Neoplasms / Q000188:drug therapy / Q000473:pathology; D051379:Mice; D008856:Microscopy, Fluorescence; D009336:Necrosis; D010569:Perylene / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000633:toxicity; D051381:Rats; D012509:Sarcoma / Q000188:drug therapy / Q000473:pathology; D000068936:Theranostic Nanomedicine; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: D000873:Anthracenes; D000970:Antineoplastic Agents; D007457:Iodine Radioisotopes; D010569:Perylene; C004965:hypericin
keywords: Autoradiography; SPECT/CT imaging; biodistribution; intra-tumoral administration; necrosis-avid theranostic agent; radioiodinated hypericin; small-molecular tumor necrosis therapy