Dose escalation immunoPET imaging of B7-H3 expression in glioblastoma tumor model using 89Zr-DFO-hu4G4

Abstract

Abstract Background The non-invasive PET imaging using zrconium-89 labelled antibodys (Abs) can play important roles for personalized immunotherapeutic strategies. Hu4G4 was a humanized Abs of the transmembrance glycoprotein B7-H3, which has been approved as an attractive new target of cancer immunotherapy. This study aimed to investigate the PET imaging potential of 89Zr labelled hu4G4 with a dose escalation design. Methods Hu4G4 was radiolabelled with 89Zr after modification with p-SCN-deferoxamine. 89Zr-Immuno-PET scans of the U87 xenograft mice were performed with 3 different Abs doses of 89Zr-DFO-hu4G4 (0.33, 1.75 and 17.5 mg/kg bodyweight, respectively). The pharmacokinetic (PK) and biodistribution profiles were also determined by γ counting of blood samples and dissected organs and tissues. Results The prepared 89Zr-DFO-hu4G4 had high radiochemical purity (RCP > 95%) and was stable in vitro (RCP > 90% within 168 h). The U87 tumors were clearly detected by the 89Zr-DFO-hu4G4 PET imaging. The middle-dose Abs group had higher tumor-to-normal tissue (T/N) ratios and better tumor specific uptake of the tracer than the low and high dose Abs groups. Conclusion 89Zr-DFO-hu4G4 is a potential immunoPET imaging probe for clinical detection of B7-H3 expression in tumor. Also, the dose dependent results of 89Zr-immuno-PET imaging provide important insight towards the Abs dosimetry for Abs-based imaging and therapy.