Validation of [89Zr]Zr-oxine labelling and PET/CT imaging for tracking mesenchymal stem cells in mice and patients with perianal fistula

Abstract

Allogeneic umbilical cord-derived mesenchymal stem cells (TH-SC01) hold promise for treating perianal fistulas (pf) in Crohn’s disease (pfCD); however, like other live-cell products, their in vivo behaviour remains unclear. Zirconium-89 ([ 89 Zr]Zr)-oxine positron emission tomography was used to track TH-SC01 cells after local perianal administration to NOG mice and three male patients with pf. Moreover, we comprehensively characterized the pharmacodynamic, pharmacokinetic, safety, biodistribution, and organ dosimetry profiles of [ 89 Zr]Zr-oxine-TH-SC01 cells. In normal mice, [ 89 Zr]Zr-oxine-TH-SC01 cells exhibited high perianal retention (> 25% at 168 h). A pilot clinical study (comprising three patients, one with pfCD) showed sustained perianal localisation: > 60% perianal retention at 60 h and ~ 20% at 400 h; minimal systemic spread (SUV mean < 3.5); and significant draining lymph node uptake. Pharmacokinetic analysis confirmed the prolonged residence time at the target site (T 1/2 = 376.17 ± 183.78 h). The preliminary 24-week efficacy was suggestive (one complete remission), and no serious adverse events were noted throughout the observation period. Collectively, these findings verify that cell tracking with [⁸⁹Zr]Zr-oxine is safe and feasible. Additionally, MSCs can persist within local tissue for an extended duration following perianal administration, a phenomenon that may underpin the therapeutic efficacy of MSCs for anal fistula.