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 - 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 -