Title: A Dual-targeting Anticancer Approach: Soil and Seed Principle
Authors: Li, Junjie
Sun, Ziping
Zhang, Jian
Shao, Haibo
Miranda Cona, Marlein #
Wang, Huaijun
Marysael, Thierry
Chen, Feng
Prinsen, Kristof
Zhou, Lin
Huang, Dejian
Nuyts, Johan
Yu, Jie
Meng, Bin
Bormans, Guy
Fang, Zhijun
de Witte, Peter
Li, Yaming
Verbruggen, Alfons
Wang, Xiaoning
Mortelmans, Luc
Xu, Ke
Marchal, Guy
Ni, Yicheng # ×
Issue Date: Sep-2011
Publisher: Radiological Society of North America
Series Title: Radiology vol:260 issue:3 pages:799-807
Abstract: Purpose: To test the hypothesis that targeting the microenvironment (soil) may effectively kill cancer cells (seeds) through a small-molecular weight sequential dual-targeting theragnostic strategy, or dual-targeting approach. Materials and Methods: With approval from the institutional animal care and use committee, 24 rats were implanted with 48 liver rhabdomyosarcomas (R1). First, the vascular-disrupting agent combretastatin A4 phosphate (CA4P) was injected at a dose of 10 mg/kg to cause tumor necrosis, which became a secondary target. Then, the necrosis-avid agent hypericin was radiolabeled with iodine 131 to form I-131-hypericin, which was injected at 300 MBq/kg 24 hours after injection of CA4P. Both molecules have small molecular weight, are naturally or synthetically derivable, are intravenously injectable, and are of unique targetablities. The tumor response in the dual-targeting group was compared with that in vehicle-control and single-targeting (CA4P or I-131-hypericin) groups with in vivo magnetic resonance imaging and scintigrams and ex vivo gamma counting, autoradiography, and histologic analysis. Tumor volumes, tumor doubling time (TDT), and radiobiodistribution were analyzed with statistical software. P values below .05 were considered to indicate a significant difference. Results: Eight days after treatment, the tumor volume of rhabdomyosarcoma in the vehicle-control group was double that in both single-targeting groups (P <.001) and was five times that in the dual-targeting group (P <.0001), without treatment-related animal death. The TDT was significantly longer in the dual-targeting group (P <.0001). Necrosis appeared as hot spots on scintigrams, corresponding to 3.13% of the injected dose of I-131-hypericin per gram of tissue (interquartile range, 2.92%-3.97%) and a target-to-liver ratio of 20. The dose was estimated to be 100 times the cumulative dose of 50 Gy needed for radiotherapeutic response. Thus, accumulated I-131-hypericin from CA4P-induced necrosis killed residual cancer cells with ionizing radiation and inhibited tumor regrowth. Conclusion: This dual-targeting approach may be a simple and workable solution for cancer treatment and deserves further exploitation. (C) RSNA, 2011
ISSN: 0033-8419
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Nuclear Medicine & Molecular Imaging
Theragnostic Laboratory (+)
× corresponding author
# (joint) last author

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