Radiolabeling of human mesenchymal stem cells for imaging of intraarterial delivery to the brain

Abstract

Intra-arterial delivery of cellular therapies might be highly beneficial due to the first-pass effect, lowering total cell dose; however, imaging might be instrumental in achieving high precision. Magnetic labeling was used for this purpose, but it interferes with diagnostic MRI and has low specificity on follow-up scans. Radiolabeling and PET imaging may address both drawbacks, although radiolabeling conditions were never studied systematically, and efficiencies needed to be higher to adapt methods of low- dose intra-arterial interventions. We hypothesize that radiolabeling of human mesenchymal stem cells (hMSCs) might be beneficial by yielding higher sensitivity over a longer period and will provide quantitative results. Therefore, the goal of the current project is to investigate clinically applicable methods for cell tracking. Moreover, we employ a modern radioisotope 89Zr, which allows for long-term (up to 2 weeks) cell biodistribution in the body. Specifically, the radiolabeling will reveal the retention capacities of transfected cells in the target organ (brain) but can also assess the off- target destination of transplanted cells in live animals.