TY - JOUR
T1 - Evaluation of 70–150-μm doxorubicin-eluting beads for transcatheter arterial chemoembolization in the rabbit liver VX2 tumour model
AU - Gholamrezanezhad, Ali
AU - Mirpour, Sahar
AU - Geschwind, Jean Francois H.
AU - Rao, Pramod
AU - Loffroy, Romaric
AU - Pellerin, Olivier
AU - Liapi, Eleni A.
N1 - Funding Information:
The scientific guarantor of this publication is Jean-Francois Geschwind, M.D. The authors of this manuscript declare relationships with the following companies: Biocompatibles, PLC; Guerbet, LLC, Philips Healthcare. This study has received funding by Biocompatibles, PLC. No complex statistical methods were necessary for this paper. Institutional review board approval was not required because this is an animal study. Written informed consent was obtained from all subjects (patients) in this study. Written informed consent was waived by the Institutional Review Board. Approval from the institutional animal care committee was obtained. Study subjects or cohorts have not been previously reported. Methodology: prospective, experimental, performed at one institution.
Publisher Copyright:
© 2016, European Society of Radiology.
PY - 2016/10/1
Y1 - 2016/10/1
N2 - 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.
AB - 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.
KW - Doxorubicin
KW - Drug-eluting beads, DEBs
KW - Injections, intra-arterial
KW - Liver neoplasms
KW - Microspheres
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U2 - 10.1007/s00330-015-4197-y
DO - 10.1007/s00330-015-4197-y
M3 - Article
C2 - 26780638
AN - SCOPUS:84954423120
SN - 0938-7994
VL - 26
SP - 3474
EP - 3482
JO - European Radiology
JF - European Radiology
IS - 10
ER -