PVA-Microbubbles as a Radioembolization Platform: Formulation and the In Vitro Proof of Concept

This proof-of-concept study lays the foundations for the development of a delivery strategy for radioactive lanthanides, such as Yttrium-90, against recurrent glioblastoma. Our appealing hypothesis is that by taking advantage of the combination of biocompatible polyvinyl alcohol (PVA) microbubbles (MBs) and endovascular radiopharmaceutical infusion, a minimally invasive selective radioembolization can be achieved, which can lead to personalized treatments limiting off-target toxicities for the normal brain. The results show the successful formulation strategy that turns the ultrasound contrast PVA-shelled microbubbles into a microdevice, exhibiting good loading efficiency of Yttrium cargo by complexation with a bifunctional chelator. The selective targeting of Yttrium-loaded MBs on the glioblastoma-associated tumor endothelial cells can be unlocked by the biorecognition between the overexpressed alpha(V)beta(3) integrin and the ligand Cyclo(Arg-Gly-Asp-D-Phe-Lys) at the PVA microbubble surface. Hence, we show the suitability of PVA MBs as selective Y-microdevices for in situ injection via the smallest (i.e., 1.2F) neurointerventional microcatheter available on the market and the accumulation of PVA MBs on the HUVEC cell line model of integrin overexpression, thereby providing similar to 6 x 10(-15) moles of Y90 per HUVEC cell. We further discuss the potential impact of using such versatile PVA MBs as a new therapeutic chance for treating glioblastoma multiforme recurrence.

Automated summary

This proof-of-concept study establishes a delivery strategy for radioactive lanthanides against recurrent glioblastoma using biocompatible PVA microbubbles and endovascular radiopharmaceutical infusion. The successful formulation turns PVA microbubbles into a microdevice with efficient Yttrium cargo loading. The selective targeting of Yttrium-loaded microbubbles on glioblastoma-associated tumor endothelial cells is achieved through biorecognition between overexpressed alpha(V)beta(3) integrin and the ligand Cyclo(Arg-Gly-Asp-D-Phe-Lys) on the microbubble surface.