Hyperthermia-mediated doxorubicin release from thermosensitive liposomes using MR-HIFU: Therapeutic effect in rabbit Vx2 tumours

Robert M. Staruch, Kullervo Hynynen, Rajiv Chopra

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

Purpose: The aim of this study was to determine whether localised drug release using thermosensitive liposomal doxorubicin (TLD) and mild hyperthermia produced by a clinical magnetic resonance high intensity focused ultrasound (MR-HIFU) system improves anti-tumour efficacy over TLD alone in rabbit Vx2 tumours. Materials and methods: Rabbits bearing one Vx2 thigh tumour (n=6 per group) were administered TLD (1.67 mg/kg) either with or without MR-HIFU mild hyperthermia (20 min, 42.0 °C). Tumour progression was measured using contrast-enhanced T1-weighted MR imaging. Toxicity was evaluated by changes in body weight, blood counts, and blood chemistry. Tumour volume, body weight, and blood data were acquired weekly for the first month and biweekly thereafter. Results: Rabbits treated with TLD plus MR-HIFU mild hyperthermia had target region temperatures with spatial-median, temporal-mean of 41.4° ± 0.6 °C; 10th and 90th percentile temperatures were 40.2 and 42.7 °C. All six rabbits that received TLD alone had rapid tumour progression and reached the tumour size end point (maximum dimension >6 cm) within 24 days. Four of six rabbits treated with TLD plus MR-HIFU mild hyperthermia survived to the study end point of 60 days; one reached tumour size end point, one had hyperthermia-related toxicity, all had at least a transient decrease in tumour volume. Weekly body weight, complete blood counts, and blood chemistry did not reveal additional evidence of drug or hyperthermia-related toxicity. Conclusions: Rabbit Vx2 tumours treated with a single infusion of TLD during MR-HIFU mild hyperthermia had reduced tumour growth vs. tumours treated with TLD alone. These findings are an important step toward clinical translation of localised drug delivery using MR-HIFU and TLD.

Original languageEnglish (US)
Pages (from-to)118-133
Number of pages16
JournalInternational Journal of Hyperthermia
Volume31
Issue number2
DOIs
StatePublished - Mar 1 2015

Fingerprint

Therapeutic Uses
Liposomes
Doxorubicin
Fever
Magnetic Resonance Spectroscopy
Rabbits
Neoplasms
Tumor Burden
Body Weight
liposomal doxorubicin
Body Weight Changes
Temperature
Blood Cell Count
Thigh
Pharmaceutical Preparations

Keywords

  • Heat targeted drug delivery
  • High intensity focused ultrasound
  • Image-guided therapy
  • Non-invasive thermometry
  • Prediction and monitoring of tumour response

ASJC Scopus subject areas

  • Cancer Research
  • Physiology
  • Radiological and Ultrasound Technology
  • Physiology (medical)

Cite this

Hyperthermia-mediated doxorubicin release from thermosensitive liposomes using MR-HIFU : Therapeutic effect in rabbit Vx2 tumours. / Staruch, Robert M.; Hynynen, Kullervo; Chopra, Rajiv.

In: International Journal of Hyperthermia, Vol. 31, No. 2, 01.03.2015, p. 118-133.

Research output: Contribution to journalArticle

@article{f1f7f14c26a44c2db882134f7dbdfca6,
title = "Hyperthermia-mediated doxorubicin release from thermosensitive liposomes using MR-HIFU: Therapeutic effect in rabbit Vx2 tumours",
abstract = "Purpose: The aim of this study was to determine whether localised drug release using thermosensitive liposomal doxorubicin (TLD) and mild hyperthermia produced by a clinical magnetic resonance high intensity focused ultrasound (MR-HIFU) system improves anti-tumour efficacy over TLD alone in rabbit Vx2 tumours. Materials and methods: Rabbits bearing one Vx2 thigh tumour (n=6 per group) were administered TLD (1.67 mg/kg) either with or without MR-HIFU mild hyperthermia (20 min, 42.0 °C). Tumour progression was measured using contrast-enhanced T1-weighted MR imaging. Toxicity was evaluated by changes in body weight, blood counts, and blood chemistry. Tumour volume, body weight, and blood data were acquired weekly for the first month and biweekly thereafter. Results: Rabbits treated with TLD plus MR-HIFU mild hyperthermia had target region temperatures with spatial-median, temporal-mean of 41.4° ± 0.6 °C; 10th and 90th percentile temperatures were 40.2 and 42.7 °C. All six rabbits that received TLD alone had rapid tumour progression and reached the tumour size end point (maximum dimension >6 cm) within 24 days. Four of six rabbits treated with TLD plus MR-HIFU mild hyperthermia survived to the study end point of 60 days; one reached tumour size end point, one had hyperthermia-related toxicity, all had at least a transient decrease in tumour volume. Weekly body weight, complete blood counts, and blood chemistry did not reveal additional evidence of drug or hyperthermia-related toxicity. Conclusions: Rabbit Vx2 tumours treated with a single infusion of TLD during MR-HIFU mild hyperthermia had reduced tumour growth vs. tumours treated with TLD alone. These findings are an important step toward clinical translation of localised drug delivery using MR-HIFU and TLD.",
keywords = "Heat targeted drug delivery, High intensity focused ultrasound, Image-guided therapy, Non-invasive thermometry, Prediction and monitoring of tumour response",
author = "Staruch, {Robert M.} and Kullervo Hynynen and Rajiv Chopra",
year = "2015",
month = "3",
day = "1",
doi = "10.3109/02656736.2014.992483",
language = "English (US)",
volume = "31",
pages = "118--133",
journal = "International Journal of Hyperthermia",
issn = "0265-6736",
publisher = "Informa Healthcare",
number = "2",

}

TY - JOUR

T1 - Hyperthermia-mediated doxorubicin release from thermosensitive liposomes using MR-HIFU

T2 - Therapeutic effect in rabbit Vx2 tumours

AU - Staruch, Robert M.

AU - Hynynen, Kullervo

AU - Chopra, Rajiv

PY - 2015/3/1

Y1 - 2015/3/1

N2 - Purpose: The aim of this study was to determine whether localised drug release using thermosensitive liposomal doxorubicin (TLD) and mild hyperthermia produced by a clinical magnetic resonance high intensity focused ultrasound (MR-HIFU) system improves anti-tumour efficacy over TLD alone in rabbit Vx2 tumours. Materials and methods: Rabbits bearing one Vx2 thigh tumour (n=6 per group) were administered TLD (1.67 mg/kg) either with or without MR-HIFU mild hyperthermia (20 min, 42.0 °C). Tumour progression was measured using contrast-enhanced T1-weighted MR imaging. Toxicity was evaluated by changes in body weight, blood counts, and blood chemistry. Tumour volume, body weight, and blood data were acquired weekly for the first month and biweekly thereafter. Results: Rabbits treated with TLD plus MR-HIFU mild hyperthermia had target region temperatures with spatial-median, temporal-mean of 41.4° ± 0.6 °C; 10th and 90th percentile temperatures were 40.2 and 42.7 °C. All six rabbits that received TLD alone had rapid tumour progression and reached the tumour size end point (maximum dimension >6 cm) within 24 days. Four of six rabbits treated with TLD plus MR-HIFU mild hyperthermia survived to the study end point of 60 days; one reached tumour size end point, one had hyperthermia-related toxicity, all had at least a transient decrease in tumour volume. Weekly body weight, complete blood counts, and blood chemistry did not reveal additional evidence of drug or hyperthermia-related toxicity. Conclusions: Rabbit Vx2 tumours treated with a single infusion of TLD during MR-HIFU mild hyperthermia had reduced tumour growth vs. tumours treated with TLD alone. These findings are an important step toward clinical translation of localised drug delivery using MR-HIFU and TLD.

AB - Purpose: The aim of this study was to determine whether localised drug release using thermosensitive liposomal doxorubicin (TLD) and mild hyperthermia produced by a clinical magnetic resonance high intensity focused ultrasound (MR-HIFU) system improves anti-tumour efficacy over TLD alone in rabbit Vx2 tumours. Materials and methods: Rabbits bearing one Vx2 thigh tumour (n=6 per group) were administered TLD (1.67 mg/kg) either with or without MR-HIFU mild hyperthermia (20 min, 42.0 °C). Tumour progression was measured using contrast-enhanced T1-weighted MR imaging. Toxicity was evaluated by changes in body weight, blood counts, and blood chemistry. Tumour volume, body weight, and blood data were acquired weekly for the first month and biweekly thereafter. Results: Rabbits treated with TLD plus MR-HIFU mild hyperthermia had target region temperatures with spatial-median, temporal-mean of 41.4° ± 0.6 °C; 10th and 90th percentile temperatures were 40.2 and 42.7 °C. All six rabbits that received TLD alone had rapid tumour progression and reached the tumour size end point (maximum dimension >6 cm) within 24 days. Four of six rabbits treated with TLD plus MR-HIFU mild hyperthermia survived to the study end point of 60 days; one reached tumour size end point, one had hyperthermia-related toxicity, all had at least a transient decrease in tumour volume. Weekly body weight, complete blood counts, and blood chemistry did not reveal additional evidence of drug or hyperthermia-related toxicity. Conclusions: Rabbit Vx2 tumours treated with a single infusion of TLD during MR-HIFU mild hyperthermia had reduced tumour growth vs. tumours treated with TLD alone. These findings are an important step toward clinical translation of localised drug delivery using MR-HIFU and TLD.

KW - Heat targeted drug delivery

KW - High intensity focused ultrasound

KW - Image-guided therapy

KW - Non-invasive thermometry

KW - Prediction and monitoring of tumour response

UR - http://www.scopus.com/inward/record.url?scp=84928190321&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84928190321&partnerID=8YFLogxK

U2 - 10.3109/02656736.2014.992483

DO - 10.3109/02656736.2014.992483

M3 - Article

C2 - 25582131

AN - SCOPUS:84928190321

VL - 31

SP - 118

EP - 133

JO - International Journal of Hyperthermia

JF - International Journal of Hyperthermia

SN - 0265-6736

IS - 2

ER -