Evaluation of 70-150-[mu]m doxorubicin-eluting beads for transcatheter arterial chemoembolization in the rabbit liver VX2 tumour model

Aim To evaluate the pharmacokinetic profile (PK) and embolization effect of 70-150-[mu]m doxorubicin eluting beads (DEBs) following intra-arterial injection (i.a.) in the rabbit liver VX2 tumour model. Materials and methods In this ACUC-approved study, 25 white New Zealand rabbits were randomly assigned into a small DEB group (SDB, n=7, 70-150-[mu]m DEBs), large DEB group (LDB, n=7, 100-300-[mu]m DEBs), untreated controls (n=7), and doxorubicin controls (n=4, without tumour, received i.a. 12.5 mg doxorubicin). Plasma PK was assessed up to 180 min post-injection. Drug tissue and liver enzyme levels, radiologic tumor response and histopathologic tumour necrosis were assessed at 7 days. Results Mean tumour doxorubicin concentrations were 922.83 nM (SD=722.05) and 361.48 nM (SD=473.23) for the SDB and LDB, respectively (p=0.005). There was no statistically significant difference in tumour doxorubicinol, plasma doxorubicin and doxorubicinol PK values. More beads were observed in the SDB tumours (p=0.01). Liver enzymes increased and gradually declined over the observation period, with significantly higher values in the SDB. Conclusion In this preclinical study, plasma PK of i.a.-injected 70-150-[mu]m DEBs was not different than that of 100-300-[mu]m DEBs. More beads and higher tissue doxorubicin levels were observed in the SDB tumours. Key Points * Small and large doxorubicin-eluting beads show similar plasma pharmacokinetic profiles. * Higher tissue doxorubicin levels were observed in the small bead group. * Liver enzymes were overall significantly higher in the small bead group.