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Abstract No. 156: Diffusion of Doxorubicin from Drug Eluting Beads and Tissular Changes After Embolisation of Hepatocellular Carcinoma
DEB, the position of the infrared peak corresponding to sulfonate moiety was shifted compared to the position of the peak in control unloaded DEB, demonstrating that both DOXO and CPT11 interact with DEB via the sulfonate groups.
crometers from the bead. DOXO concentration correlates with tissular changes.
CONCLUSION: Infrared microspectroscopy demonstrates that DOXO and CPT11 both interact with DEB through ionic binding. Depending on the amount of sulphonate fixed in DEB, the concentration and distribution of the drug may be controlled.
Irinotecan Concentration in Drug Eluting Beads After 2 Hours and 24 Hours of Loading. J. Namur1, H. Dinca1, M. Baylatry2, A.L. Lewis3, M. Manfait1, A. Laurent4; 1Me´DIAN UMR CNRS 6237, Reims, France; 2Saint-Antoine Hospital, Paris, France; 3 Biocompatibles UK Ltd, Farnham, United Kingdom; 4 Lariboisiere Hospital, Paris, France.
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Abstract No. 156
MATERIALS & METHODS: The material consisted of liver samples from a clinical study of DOXO bead chemoembolization conducted at Piedmont Hospital, Atlanta GA, USA. Briefly, six patients underwent left hepatic artery embolisation with DOXO beads (LC/DC Bead™ Biocompatibles UK Ltd, size: 100-300m, mean dose of drug injected: 98.3⫾24.4mg, 75-150mg) prior to liver transplantation (mean time of explantation: 17.5⫾11days, 1-36days). Samples were taken from explanted livers and processed for pathology. On 5m thick liver slides, DOXO fluorescence was recorded with microspectrofluorimetry (M51, Dilor) from the tissue up to a distance of 600m from the edge of the bead (n⫽162). The tissular concentration of DOXO (tissCDOXO) was estimated with standard DOXO collagen phantoms. The tissCDOXO were compared statistically according to time of explantation at 3 periods : 1 day (n⫽1 patient), 9-14 days (n⫽3), 32-36 days (n⫽2). Tissular changes were noted. RESULTS: The drug was detected in the tissue surrounding the beads for all times of explantation. The tissCDOXO decreased exponentially with the distance from the bead (mean for all samples at 20m from the bead: 1.2⫾1.1mol/L; at 600m: 0.4⫾0.5mol/L). The tissCDOXO decreased significantly with the time of explantation (decrease between 1 day and 32-36 days at 20m: 80%; at 600m: 90%, p⬍.0001 Mann Whitney). Necrosis was present at periods 2 and 3, but could not be evaluated at period 1. There was a good correlation between DOXO concentration and the necrosis. CONCLUSION: Cytostatic levels of DOXO are found in the tissue surrounding the beads up to several hundred mi-
PURPOSE: Drug eluting beads (DEB) are being proposed in TACE procedures for the treatment of liver cancers. Drug loading is performed extemporaneously a few hours before embolization by simply mixing the DEB and the drug solution. The aim of the present work was to assess the concentration of the camptothecin Irinotecan (CPT11) loaded in drug eluting beads after 2 hours and 24 hours of infusion. MATERIALS & METHODS: DEB made of polyvinyl alcohol modified with sulphonate groups (DC-BeadsTM, 100300m, Biocompatibles UK Ltd) were loaded with a solution of CPT11 (Camptosar® 2mg/mL, Pfizer) according to instructions for loading. Saline was removed from the vial of DEB and a volume of CPT11 was added to the vial at a target dose of 50mg CPT11 /mL bead. The vials were left at room temperature in the dark without agitation for 2 hours or 24 hours. CPT11 concentration was then determined inside the DEB using infrared microspectroscopy as previously described for the drug Ibuprofen (Namur et al. JVIR 2008, 19(2) S55-S56). RESULTS: IR-MS showed a good sensitivity (limit of quantification ⫽ 5mg/mL) and a good linearity (correlation coefficient R ⫽ 0.960) for CPT11 quantification. Drug concentration as determined with IR-MS was respectively 79⫾11 % and 94⫾5 % of target dose after 2 hours and 24 hours of loading (p⬍0.05 MW). CONCLUSION: The time of infusion required to achieve a 50mg/mL loaded dose seems to be longer than the prescribed 2 hours. 5:24 PM
Abstract No. 158
Elution Characteristics of Doxorubicin of Super Absorbant Polymer Microspheres: Ex Vivo Study. D.M. Liu1,2, S.G. Ho1, C. Loh3, G. Legiehn3, P.L. Munk1, R. Salem3, S. Kee2; 1Vancouver General Hospital University of British Columbia, Vancouver, BC, Canada; 2Ronald Reagan UCLA Medical Center, Los Angeles, CA; 3Northwestern Memorial Hospital, Chicago, IL. PURPOSE: The application and efficacy of superabsorbant microspheres (SAP) as bland embolics in the treatment of hypervascular tumors, and hepatocellular carcinoma has been previously described. Uptake and elution of doxorubicin through an ion exchange mechanism has been observed. The purpose of this study is to examine the characteristics of SAP as it relates to doxorubicin loading and elution. MATERIALS & METHODS: 11 combinations of microspheres including loading during dry vs prehydrated, size, hydration protocol and method of doxorubicin reconstitution were explored in an ex vivo model. HLPC was utilized to determine the time dependant elution into buffer for all S61
TUESDAY
PURPOSE: We have previously demonstrated in a nontumorous pig liver model that embolization beads loaded with Doxorubicin (DOXO) effectively deliver high amounts of drug in surrounding tissues (up to 2mol/L) (Namur et al. JVIR 2008, 19(2) S19). Our objective was to assess the amount of DOXO released in explanted livers from patients with hepatocellular carcinoma (HCC) embolized prior to transplantation.
Abstract No. 157
Scientific Sessions
Diffusion of Doxorubicin from Drug Eluting Beads and Tissular Changes After Embolisation of Hepatocellular Carcinoma. J. Namur1, S.J. Citron2, M. Dupuis3, M.T. Sellers4, M. Wassef5, M. Manfait1, A. Laurent6; 1Me´DIAN UMR CNRS 6237, Reims, France; 2Piedmont Hospital - Radiology, Atlanta, GA; 3Piedmont Hospital - Pathology, Atlanta, GA; 4Piedmont Hospital - Transplantation Surgery, Atlanta, GA; 5Lariboisiere Hospital - Pathology, Paris, France; 6Lariboisiere Hospital - Neuroradiology, Paris, France.
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crometers from the bead. DOXO concentration correlates with tissular changes.
CONCLUSION: Infrared microspectroscopy demonstrates that DOXO and CPT11 both interact with DEB through ionic binding. Depending on the amount of sulphonate fixed in DEB, the concentration and distribution of the drug may be controlled.
Irinotecan Concentration in Drug Eluting Beads After 2 Hours and 24 Hours of Loading. J. Namur1, H. Dinca1, M. Baylatry2, A.L. Lewis3, M. Manfait1, A. Laurent4; 1Me´DIAN UMR CNRS 6237, Reims, France; 2Saint-Antoine Hospital, Paris, France; 3 Biocompatibles UK Ltd, Farnham, United Kingdom; 4 Lariboisiere Hospital, Paris, France.
5:00 PM
Abstract No. 156
MATERIALS & METHODS: The material consisted of liver samples from a clinical study of DOXO bead chemoembolization conducted at Piedmont Hospital, Atlanta GA, USA. Briefly, six patients underwent left hepatic artery embolisation with DOXO beads (LC/DC Bead™ Biocompatibles UK Ltd, size: 100-300m, mean dose of drug injected: 98.3⫾24.4mg, 75-150mg) prior to liver transplantation (mean time of explantation: 17.5⫾11days, 1-36days). Samples were taken from explanted livers and processed for pathology. On 5m thick liver slides, DOXO fluorescence was recorded with microspectrofluorimetry (M51, Dilor) from the tissue up to a distance of 600m from the edge of the bead (n⫽162). The tissular concentration of DOXO (tissCDOXO) was estimated with standard DOXO collagen phantoms. The tissCDOXO were compared statistically according to time of explantation at 3 periods : 1 day (n⫽1 patient), 9-14 days (n⫽3), 32-36 days (n⫽2). Tissular changes were noted. RESULTS: The drug was detected in the tissue surrounding the beads for all times of explantation. The tissCDOXO decreased exponentially with the distance from the bead (mean for all samples at 20m from the bead: 1.2⫾1.1mol/L; at 600m: 0.4⫾0.5mol/L). The tissCDOXO decreased significantly with the time of explantation (decrease between 1 day and 32-36 days at 20m: 80%; at 600m: 90%, p⬍.0001 Mann Whitney). Necrosis was present at periods 2 and 3, but could not be evaluated at period 1. There was a good correlation between DOXO concentration and the necrosis. CONCLUSION: Cytostatic levels of DOXO are found in the tissue surrounding the beads up to several hundred mi-
PURPOSE: Drug eluting beads (DEB) are being proposed in TACE procedures for the treatment of liver cancers. Drug loading is performed extemporaneously a few hours before embolization by simply mixing the DEB and the drug solution. The aim of the present work was to assess the concentration of the camptothecin Irinotecan (CPT11) loaded in drug eluting beads after 2 hours and 24 hours of infusion. MATERIALS & METHODS: DEB made of polyvinyl alcohol modified with sulphonate groups (DC-BeadsTM, 100300m, Biocompatibles UK Ltd) were loaded with a solution of CPT11 (Camptosar® 2mg/mL, Pfizer) according to instructions for loading. Saline was removed from the vial of DEB and a volume of CPT11 was added to the vial at a target dose of 50mg CPT11 /mL bead. The vials were left at room temperature in the dark without agitation for 2 hours or 24 hours. CPT11 concentration was then determined inside the DEB using infrared microspectroscopy as previously described for the drug Ibuprofen (Namur et al. JVIR 2008, 19(2) S55-S56). RESULTS: IR-MS showed a good sensitivity (limit of quantification ⫽ 5mg/mL) and a good linearity (correlation coefficient R ⫽ 0.960) for CPT11 quantification. Drug concentration as determined with IR-MS was respectively 79⫾11 % and 94⫾5 % of target dose after 2 hours and 24 hours of loading (p⬍0.05 MW). CONCLUSION: The time of infusion required to achieve a 50mg/mL loaded dose seems to be longer than the prescribed 2 hours. 5:24 PM
Abstract No. 158
Elution Characteristics of Doxorubicin of Super Absorbant Polymer Microspheres: Ex Vivo Study. D.M. Liu1,2, S.G. Ho1, C. Loh3, G. Legiehn3, P.L. Munk1, R. Salem3, S. Kee2; 1Vancouver General Hospital University of British Columbia, Vancouver, BC, Canada; 2Ronald Reagan UCLA Medical Center, Los Angeles, CA; 3Northwestern Memorial Hospital, Chicago, IL. PURPOSE: The application and efficacy of superabsorbant microspheres (SAP) as bland embolics in the treatment of hypervascular tumors, and hepatocellular carcinoma has been previously described. Uptake and elution of doxorubicin through an ion exchange mechanism has been observed. The purpose of this study is to examine the characteristics of SAP as it relates to doxorubicin loading and elution. MATERIALS & METHODS: 11 combinations of microspheres including loading during dry vs prehydrated, size, hydration protocol and method of doxorubicin reconstitution were explored in an ex vivo model. HLPC was utilized to determine the time dependant elution into buffer for all S61
TUESDAY
PURPOSE: We have previously demonstrated in a nontumorous pig liver model that embolization beads loaded with Doxorubicin (DOXO) effectively deliver high amounts of drug in surrounding tissues (up to 2mol/L) (Namur et al. JVIR 2008, 19(2) S19). Our objective was to assess the amount of DOXO released in explanted livers from patients with hepatocellular carcinoma (HCC) embolized prior to transplantation.
Abstract No. 157
Scientific Sessions
Diffusion of Doxorubicin from Drug Eluting Beads and Tissular Changes After Embolisation of Hepatocellular Carcinoma. J. Namur1, S.J. Citron2, M. Dupuis3, M.T. Sellers4, M. Wassef5, M. Manfait1, A. Laurent6; 1Me´DIAN UMR CNRS 6237, Reims, France; 2Piedmont Hospital - Radiology, Atlanta, GA; 3Piedmont Hospital - Pathology, Atlanta, GA; 4Piedmont Hospital - Transplantation Surgery, Atlanta, GA; 5Lariboisiere Hospital - Pathology, Paris, France; 6Lariboisiere Hospital - Neuroradiology, Paris, France.
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