Effect of mAb B3 and paclitaxel doses on accumulation and penetration of B3 into tumor

1322 Objectives To investigate the effect of 1) the different doses and 2) serial fractional injections of paclitaxel (Taxol) and B3 on the accumulation and the microdistribution of B3. Methods Groups of nude mice (n=3 / group) were inoculated with Ley positive A431 tumor cells. When the tumor size reached ~200 mm3, the mice were divided into groups and were injected with 1) 150 μg or 300 μg Alexa B3 (IV) on D0, 2)serial single doses of 150 µg Alexa B3 on D0 and 40 mg/kg or 70 mg/kg Taxol (IP) on D1, and 3) serial fractional doses of 150 µg Alexa B3 on D0, 40 mg/kg Taxol on D1, 150 µg Alexa B3 on D3, and 30 mg/kg Taxol on D4 to compare with a serial single doses (300 µg Alexa B3 on D0 and 70 mg/kg on D1) . Tumors were flash frozen and sliced (8 µm) 2 days after Alexa B3 injection. Microscopic imaging was performed using a scanscope FL (pixel size;0.464 µm). B3 intensity in whole tumor and penetration (~1 mm) from the tumor edge were calculated. Results The analysis showed that 1) 2 times greater amount of B3 was accumulated in whole tumor with deeper penetration toward the tumor center when 300 µg B3 was injected compared to 150 µg B3, and 2) both 70 mg/kg and 40 mg/kg of single Taxol injection increased the total B3 accumulation in tumor by 90% compared to B3 without Taxol. The high Taxol dose produced deeper B3 penetration than low dose, and 3) there was no significant difference between the both serial doses in the total B3 accumulation in tumor, but the serial fractional injections produced deeper B3 penetration. Conclusions The serial fractional doses of B3 and Taxol produced a uniform distribution of B3 with deeper penetration than the serial single dose. This finding implies that serial fractional doses of Y-90 or Lu-177 labeled mAb and Taxol may be more efficacious regimens in producing synergistic effects in the shrinkage of solid tumors by both radio-sensitizing effect and enhanced tumor accumulation of B3.