Biodistribution and anti-tumor efficacy of intratumorally injected necrosis-avid theranostic agent radioiodinated hypericin in rodent tumor models

摘要

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 I-131-monoiodohypericin (I-131-MIH) to investigate the biodistribution of I-131-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 I-131-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 I-131-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 I-131-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 I-131-MIH. The prolonged tumor retention and effective therapy indicated that I-131-MIH may be a promising intratumorally injected SMTNT agent.