Abstract
A viable rim of tumor cells surrounding central necrosis always exists and leads to tumor recurrence after vascular disrupting treatment (VDT). A novel necrosis targeted radiotherapy (NTRT) using iodine-131-labeled hypericin (131I-Hyp) was specifically designed to treat viable tumor rim and improve tumor control after VDT in rabbit models of multifocal VX2 tumors. NTRT was administered 24 hours after VDT. Tumor growth was significantly slowed down by NTRT with a smaller tumor volume and a prolonged tumor doubling time (14.4 vs. 5.7 days), as followed by in vivo magnetic resonance imaging over 12 days. The viable tumor rims were well inhibited in NTRT group compared with single VDT control group, as showed on tumor cross sections at day 12 (1 vs. 3.7 in area). High targetability of 131I-Hyp to tumor necrosis was demonstrated by in vivo SPECT as high uptake in tumor regions lasting over 9 days with 4.26 to 98 times higher radioactivity for necrosis versus the viable tumor and other organs by gamma counting, and with ratios of 7.7-11.7 and 10.5-13.7 for necrosis over peri-tumor tissue by autoradiography and fluorescence microscopy, respectively. In conclusion, NTRT improved the anticancer efficacy of VDT in rabbits with VX2 tumors.
Highlights
Vascular disrupting treatment (VDT) has been considered a potentially important option for cancer therapy [1,2,3]
A rim of viable tumor cells survived at the periphery, despite more than 90% of the central region of tumor experiencing rapid necrosis after administration of Vascular disrupting agents (VDAs) [8]
Based on experiments in small rodents [23,24,25], we show for the first time that such medium-sized animal models can be used to verify the properties of necrosis targeted radiotherapy (NTRT)
Summary
Vascular disrupting treatment (VDT) has been considered a potentially important option for cancer therapy [1,2,3]. Vascular disrupting agents (VDAs) target the established tumor blood vessels rapidly and selectively, resulting in widespread ischemia and necrosis of the tumor [4, 5]. A rim of viable tumor cells survived at the periphery, despite more than 90% of the central region of tumor experiencing rapid necrosis after administration of VDAs [8]. These viable tumor cells are essential to tumor recurrence and metastasis. Re-growth and metastasis instead of primary tumor growth were believed to be the key contributors to the reduced overall survival benefit of cancer patients [9]
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