Evaluation of 70–150-μm doxorubicin-eluting beads for transcatheter arterial chemoembolization in the rabbit liver VX2 tumour model

• Published in: European radiology 2016-10, Vol.26 (10), p.3474-3482
• Main Authors: Gholamrezanezhad, Ali, Mirpour, Sahar, Geschwind, Jean-Francois H., Rao, Pramod, Loffroy, Romaric, Pellerin, Olivier, Liapi, Eleni A.
• Format: Article
• Language: English
• Subjects: Animals; Antibiotics, Antineoplastic - administration & dosage; Antibiotics, Antineoplastic - pharmacokinetics; Biological Physics; Chemoembolization, Therapeutic - methods; Diagnostic Radiology; Disease Models, Animal; Doxorubicin - administration & dosage; Doxorubicin - pharmacokinetics; Humans; Imaging; Injections, Intra-Arterial; Internal Medicine; Interventional; Interventional Radiology; Liver Function Tests; Liver Neoplasms, Experimental - therapy; Male; Medicine; Medicine & Public Health; Neuroradiology; Physics; Rabbits; Radiology; Treatment Outcome; Ultrasound
• ISSN: 0938-7994; 1432-1084
• DOI: 10.1007/s00330-015-4197-y

Aim To evaluate the pharmacokinetic profile (PK) and embolization effect of 70–150-μm 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-μm DEBs), large DEB group (LDB, n = 7, 100–300-μm 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-μm DEBs was not different than that of 100–300-μm 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 .