Dual Targeting Approach Reduces Tumor Volume in Rats

Thursday, August 25, 2011 (Last Updated: 08/26/2011)

THURSDAY, Aug. 25 (HealthDay News) -- A dual targeting approach, using combretastatin A4 phosphate (CA4P)-induced necrosis and iodine 131 radiolabeled necrosis-avid agent hypericin (131I-hypericin), successfully reduces tumor volume and increases tumor doubling time (TDT) in rats with liver rhabdomyosarcomas, according to an experimental study published in the September issue of Radiology.

Junjie Li, M.D., from the University of Leuven in Belgium, and colleagues investigated whether cancer cells (seed) can be killed by selectively destroying by radioactively contaminating their microenvironment (soil) through a dual-targeting approach. A total of 24 rats were implanted with 48 liver rhabdomyosarcomas followed by the administration of 10 mg/kg of CA4P to cause tumor necrosis. The 131I-hypericin, was injected 24 hours after CA4P at 300 MBq/kg. In vivo magnetic resonance imaging, scintigrams, ex vivo gamma counting, autoradiography, and histologic analysis were used to compare tumor responses in the dual-targeting group with that in the vehicle-control and single-targeting (CA4P or 131I-hypericin) groups. Tumor volumes, tumor doubling time (TDT), and radiobiodistribution were estimated.

The investigators found that after eight days of treatment, the tumor volume of rhabdomyosarcomas in the vehicle-control group was five times that of the dual-targeting group, and double that seen in either of the single-targeting groups, with no treatment-related death. The dual-targeting group had a significantly longer TDT. Scintigrams revealed hot spots of necrotic tumor which corresponded with a target-to-liver ratio of 20, and 3.13 percent of the injected dose of 131I-hypericin per gram of tissue.

"Accumulated 131I-hypericin from CA4P-induced necrosis killed residual cancer cells with ionizing radiation and inhibited tumor regrowth," the authors write.

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Specialties Hematology & Oncology

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