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Increased Duration of Heating Boosts Local Drug Deposition during Radiofrequency Ablation in Combination with Thermally Sensitive Liposomes (ThermoDox) in a Porcine Model.

Swenson CE, Haemmerich D, Maul DH, Knox B, Ehrhart N, Reed RA - PLoS ONE (2015)

Bottom Line: This may reduce recurrence and be more effective than thermal ablation alone.Each pig received a single, 50 mg/m2 dose of the clinical LTLD formulation (ThermoDox®).The mean Cmax of plasma total doxorubicin was 26.5 μg/ml at the end of the infusion.

View Article: PubMed Central - PubMed

Affiliation: Celsion Corporation, Lawrenceville, NJ, United States of America.

ABSTRACT

Introduction: Radiofrequency ablation (RFA) is used for the local treatment of liver cancer. RFA is effective for small (<3 cm) tumors, but for tumors > 3 cm, there is a tendency to leave viable tumor cells in the margins or clefts of overlapping ablation zones. This increases the possibility of incomplete ablation or local recurrence. Lyso-Thermosensitive Liposomal Doxorubicin (LTLD), is a thermally sensitive liposomal doxorubicin formulation for intravenous administration, that rapidly releases its drug content when exposed to temperatures >40°C. When used with RFA, LTLD releases its doxorubicin in the vasculature around the zone of ablation-induced tumor cell necrosis, killing micrometastases in the ablation margin. This may reduce recurrence and be more effective than thermal ablation alone.

Purpose: The purpose of this study was to optimize the RFA procedure used in combination with LTLD to maximize the local deposition of doxorubicin in a swine liver model. Pigs were anaesthetized and the liver was surgically exposed. Each pig received a single, 50 mg/m2 dose of the clinical LTLD formulation (ThermoDox®). Subsequently, ablations were performed with either 1, 3 or 6 sequential, overlapping needle insertions in the left medial lobe with total ablation time of 15, 45 or 90 minutes respectively. Two different RFA generators and probes were evaluated. After the final ablation, the ablation zone (plus 3 cm margin) was dissected out and examined for doxorubicin concentration by LC/MS and fluorescence.

Conclusion: The mean Cmax of plasma total doxorubicin was 26.5 μg/ml at the end of the infusion. Overall, increased heat time from 15 to 45 to 90 minutes shows an increase in both the amount of doxorubicin deposited (up to ~100 μg/g) and the width of the ablation target margin to which doxorubicin is delivered as determined by tissue homogenization and LC/MS detection of doxorubicin and by fluorescent imaging of tissues.

No MeSH data available.


Related in: MedlinePlus

Total areas of the ablation zones with concentrations of doxorubicin above 10 μg/g.Concentration was determined by fluorescent imaging in groups 1 (single ablation), 2 (3 overlapping ablations) and 3 (6 overlapping ablations) in study B (Covidien device) and C (Angiodynamics device).
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pone.0139752.g010: Total areas of the ablation zones with concentrations of doxorubicin above 10 μg/g.Concentration was determined by fluorescent imaging in groups 1 (single ablation), 2 (3 overlapping ablations) and 3 (6 overlapping ablations) in study B (Covidien device) and C (Angiodynamics device).

Mentions: A histogram of the pixel intensities in the region of interest (the ablation zone) of each image in studies B and C was generated and the intensity values were converted to concentrations based on the calibration curve. The total area with doxorubicin concentrations above 10 μg/g was calculated for each ablation zone in each pig and is shown graphically in Fig 10. There is a trend for increasing area above 10 μg/g in both studies between group 1 (single ablation) and groups 2 and 3 (3 and 6 overlapping ablations), but this only reaches statistical significance in study B (Covidien device).


Increased Duration of Heating Boosts Local Drug Deposition during Radiofrequency Ablation in Combination with Thermally Sensitive Liposomes (ThermoDox) in a Porcine Model.

Swenson CE, Haemmerich D, Maul DH, Knox B, Ehrhart N, Reed RA - PLoS ONE (2015)

Total areas of the ablation zones with concentrations of doxorubicin above 10 μg/g.Concentration was determined by fluorescent imaging in groups 1 (single ablation), 2 (3 overlapping ablations) and 3 (6 overlapping ablations) in study B (Covidien device) and C (Angiodynamics device).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4592068&req=5

pone.0139752.g010: Total areas of the ablation zones with concentrations of doxorubicin above 10 μg/g.Concentration was determined by fluorescent imaging in groups 1 (single ablation), 2 (3 overlapping ablations) and 3 (6 overlapping ablations) in study B (Covidien device) and C (Angiodynamics device).
Mentions: A histogram of the pixel intensities in the region of interest (the ablation zone) of each image in studies B and C was generated and the intensity values were converted to concentrations based on the calibration curve. The total area with doxorubicin concentrations above 10 μg/g was calculated for each ablation zone in each pig and is shown graphically in Fig 10. There is a trend for increasing area above 10 μg/g in both studies between group 1 (single ablation) and groups 2 and 3 (3 and 6 overlapping ablations), but this only reaches statistical significance in study B (Covidien device).

Bottom Line: This may reduce recurrence and be more effective than thermal ablation alone.Each pig received a single, 50 mg/m2 dose of the clinical LTLD formulation (ThermoDox®).The mean Cmax of plasma total doxorubicin was 26.5 μg/ml at the end of the infusion.

View Article: PubMed Central - PubMed

Affiliation: Celsion Corporation, Lawrenceville, NJ, United States of America.

ABSTRACT

Introduction: Radiofrequency ablation (RFA) is used for the local treatment of liver cancer. RFA is effective for small (<3 cm) tumors, but for tumors > 3 cm, there is a tendency to leave viable tumor cells in the margins or clefts of overlapping ablation zones. This increases the possibility of incomplete ablation or local recurrence. Lyso-Thermosensitive Liposomal Doxorubicin (LTLD), is a thermally sensitive liposomal doxorubicin formulation for intravenous administration, that rapidly releases its drug content when exposed to temperatures >40°C. When used with RFA, LTLD releases its doxorubicin in the vasculature around the zone of ablation-induced tumor cell necrosis, killing micrometastases in the ablation margin. This may reduce recurrence and be more effective than thermal ablation alone.

Purpose: The purpose of this study was to optimize the RFA procedure used in combination with LTLD to maximize the local deposition of doxorubicin in a swine liver model. Pigs were anaesthetized and the liver was surgically exposed. Each pig received a single, 50 mg/m2 dose of the clinical LTLD formulation (ThermoDox®). Subsequently, ablations were performed with either 1, 3 or 6 sequential, overlapping needle insertions in the left medial lobe with total ablation time of 15, 45 or 90 minutes respectively. Two different RFA generators and probes were evaluated. After the final ablation, the ablation zone (plus 3 cm margin) was dissected out and examined for doxorubicin concentration by LC/MS and fluorescence.

Conclusion: The mean Cmax of plasma total doxorubicin was 26.5 μg/ml at the end of the infusion. Overall, increased heat time from 15 to 45 to 90 minutes shows an increase in both the amount of doxorubicin deposited (up to ~100 μg/g) and the width of the ablation target margin to which doxorubicin is delivered as determined by tissue homogenization and LC/MS detection of doxorubicin and by fluorescent imaging of tissues.

No MeSH data available.


Related in: MedlinePlus