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

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Abstract

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.

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Abbreviations

ACUC:

Animal Care and Use Committee

AST:

Aspartate transaminase

ALT:

Alanine transaminase

AUC:

Area under the curve

Cmax:

Maximum concentration

Cm:

Centimetres

CR:

Complete response

CRPV:

Shope cottontail rabbit papillomavirus

C:

Celsius

DEB:

Doxorubicin eluting bead

DEB-TACE:

Doxorubicin-eluting bead transcatheter arterial chemoembolization

GGT:

Gamma-glutamyl transferase

GI:

Gastrointestinal

i.a.:

Intra-arterial

in:

Inches

IN:

Indiana

Kg:

Kilogram

kV:

Kilovolt

LDB:

Large DEB group

MA:

Massachusetts

Mg:

Milligrams

min:

Minutes

mRECIST:

Modified Response Evaluation Criteria in Solid Tumours

μm:

Micrometers

μL:

Microlitres

mL:

Millilitres

n:

Number

NJ:

New Jersey

nM:

Nanomolar

NWZ:

New Zealand White

PK:

Pharmacokinetic

PR:

Partial response

SDB:

Small DEB group

SD:

Standard deviation

SEM:

Standard error of the mean

TACE:

Transcatheter arterial chemoembolization

TX:

Texas

UK:

United Kingdom

USA:

United States of America

VX2:

Shope cottontail rabbit papillomavirus

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Acknowledgments

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.

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Authors and Affiliations

  1. The Russell H. Morgan Department of Radiology and Radiological Science, Division of Interventional Radiology, The Johns Hopkins Hospital, Sheikh Zayed Tower, Suite 7203, 1800 Orleans Street, Baltimore, MD, 21287, USA

    Ali Gholamrezanezhad, Sahar Mirpour, Pramod Rao, Romaric Loffroy, Olivier Pellerin & Eleni A. Liapi

  2. Department of Radiology and Biomedical Imaging, Yale University School of Medicine, PO Box 208042, 330 Cedar Street, New Haven, CT, 06520, USA

    Jean-Francois H. Geschwind

Authors
  1. Ali Gholamrezanezhad
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  2. Sahar Mirpour
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  3. Jean-Francois H. Geschwind
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  4. Pramod Rao
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  5. Romaric Loffroy
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  6. Olivier Pellerin
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  7. Eleni A. Liapi
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Corresponding author

Correspondence to Jean-Francois H. Geschwind.

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Gholamrezanezhad, A., Mirpour, S., Geschwind, JF.H. et al. Evaluation of 70–150-μm doxorubicin-eluting beads for transcatheter arterial chemoembolization in the rabbit liver VX2 tumour model. Eur Radiol 26, 3474–3482 (2016). https://doi.org/10.1007/s00330-015-4197-y

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  • DOI: https://doi.org/10.1007/s00330-015-4197-y

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