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 language | English (US) |
|---|---|
| Pages (from-to) | 118-133 |
| Number of pages | 16 |
| Journal | International Journal of Hyperthermia |
| Volume | 31 |
| Issue number | 2 |
| DOIs | |
| State | Published - Mar 1 2015 |
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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 journal › Article
}
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 -