Evaluation of a new avidin chase in murine models pre-treated with two 111In labelled biotin analogues

Purpose: the “avidin-biotin system” has been extensively studied for multiple applications to treat solid tumors. In this work, we investigated the effect of a new avidin chase, PWT- Biot1, on the uptake of two different 111In-labelled biotin derivatives in mice limbs intramuscularly pre-injected with avidin. Methods: two new biotin derivatives (r-BHD and Bis18) were radiolabelled with Indium- 111 and injected intravenously in a Balb/c mice (n=48) pretreated with an intramuscular injection of avidin in the left limb and an inert injection of Matrigel® in the right limb, as negative control. Twelve mice received 111In-r-BHD and twelve received 111In-Bis18. After 30 min, 1 h, 4 h and 24 h, 3 mice per group were anesthetized to acquire in vivo planar images, followed by ex-vivo organ counting. After the synthesis of PWT-Biot1, the same in vivo experiments were performed in two more groups of 12 mice each, but administering the PWT-Biot1 chase, for removing circulating avidin, 10 min before radiolabelled biotin injection. Results: in each group, we observed high biotin uptake in the left avidinated limb as compared to the right contralateral control limb. Biodistribution studies showed renal excretion as mainly elimination pathway for both radiopharmaceuticals. The pre-injection of PWT-Biot1 chase increased the uptake in target area of 49% and 35% at 24 h for 111In-r-BHD and 111InBis18, respectively. Furthermore, PWT-Biot1 administration significantly reduced liver activity at 1h and kidney activity at 30 min, 1 h and 4 h after the administration of both biotin derivatives. Conclusions: our results indicate that PWT-Biot1 chase, by clearing circulating avidin may significantly reduce liver and kidney irradiation and increase the radiolabelled biotin uptake in target avidinated sites.