Necrosis affinity evaluation of 131I-hypericin in a rat model of induced necrosis

摘要

Cancers are often with spontaneous or therapeutic necrosis that could be utilized as a generic target for developing new treatments. The purpose of this study was to investigate the biodistribution and pharmacokinetics of radioiodinated hypericin (Hyp), a naturally occurring compound, after intravenous (i.v.) injection in a rat model of liver and muscle necrosis (n=42), and evaluate its necrosis affinity. Hyp was labeled with 131I with labeling efficiency 99%. After incubating in solution/rat plasma for 8 days, radiochemical purity of 131I-Hyp remained 98.1 and 97.1%, respectively, indicating good in vitro stability. SPECT-CT images at 24h after i.v. injection of 131I-Hyp in rats with induced liver and muscle necrosis showed obvious tracer absorption in necrotic tissues. Biodistribution studies revealed that the percentage of the injected dose per gram of tissue (%ID/g) evolved from 1.9 %ID/g at 6h, through a maximum 3.0 %ID/g at 12h, to 1.0 %ID/g at 192h in necrotic liver. Pharmacokinetics studies revealed that the terminal elimination half-life, total body clearance and area under the curve of 131I-Hyp were 32.7h, 9.2L/h/kg and 1.6MBq/L*h, respectively. These results demonstrated that 131I-Hyp features a long blood circulation in animals and persistent retention in necrotic tissues. Therefore, 131I-labeled Hyp could be a broad-spectrum anti-tumor agent with a cost much cheaper relative to the biological agents such as monoclonal antibodies.