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Magnetic resonance imaging characteristics of imageable embolic microspheres
S80
’
Monday
Scientific Session
Results: The use of fluoroscopy illustrated the high visibility and equivalent spatial distribution of the imageable microspheres compared to the control. Micro-CT analysis indicated that the imageable microspheres provide for excellent distribution and packing throughout the renal vasculature. Histology evaluation for all treated animals showed vessel occlusion with infarction of the embolized kidney pole without additional adverse tissue reaction. Conclusion: The imageable microspheres prepared in this study allowed immediate in vivo visual monitoring of their spatial distribution and embolization effectiveness inside target organs during the procedure. Thus, the safety and efficacy of these imageable microspheres were proven. Reference
MONDAY: Scientific Sessions
5:18 PM
Abstract No. 170
Magnetic resonance imaging characteristics of imageable embolic microspheres R. Abraham1,5, H. Basseri2, C. Davis3,4, E. Tonkopi1, S. Kehoe5, D. Boyd1,5, C. Bowen1,3; 1Diagnostic Imaging and Interventional Radiology, QEII Health Sciences Center, Halifax, NS, Canada; 2Department of Radiology, McMaster University, Hamilton, ON, Canada; 3 Biomedical Translational Imaging Center (BIOTIC), Halifax, NS, Canada; 4IWK Health Center, Halifax, NS, Canada; 5ABK Biomedical Incorporated, Halifax, NS, Canada Purpose: To evaluate magnetic resonance imaging (MRI) contrast produced by novel imageable embolic microspheres. Materials and Methods: Imageable microspheres, synthesized from a multicomponent bioglass as per Kehoe et al.1 were dispersed at varying concentrations (10, 20, 30, 40, 50% w/w, n¼5) in 8% porcine gelatin and subsequently loaded in 5mm Nuclear Magnetic Resonance (NMR) tubes. These suspensions were subjected to magnetic stirring, heating (o701C) and horizontal rotation (to prevent gravitational settling of the microspheres) prior to rapid cooling on ice to solidify the gel. Measurements of MRI susceptometry2, R2* (spectral linewidth), R2 (CPMG) and R1 (arrayed inversion recovery) were measured for all samples at room temperature using an Agilent 3T preclinical MRI. Values for pure microspheres were obtained from linear regression analysis of each parameter and extrapolation to 100% volume fraction (Vf). Results: Imageable microsphere measurements showed extrapolated pure microsphere values (100% Vf) for susceptometry (2.49 ppm), DR2* (683 s-1), DR2 (2.00 s-1) and DR1 (0.57 s-1). Negligible impact on clinical T1 or T2 scans would be expected even with 100% Vf (T1/T2 of 1.75s/500 ms for an ideal medium with infinite T1, T2). The MRI contrast mechanism for these microspheres is exclusively BMS contrast, with BMS theory2 predicting low R1, R2 enhancement, and R2* of 804 s-1*Vf (consistent with measurements of 683 s-1*Vf). These imageable microspheres may be visible (100% Vf corresponding to T2* of 1.5ms) and quantifiable (Vf¼R2*/683s-1) in vivo using high resolution R2* mapping body MRI protocols. Conclusion: The imageable microspheres studied have diamagnetic susceptibility with BMS contrast resulting in very low
JVIR
T1 and T2 contrast to confound most clinical scans with opportunity to visualize and quantify the microspheres using R2* mapping protocols. References 1. S Kehoe et al, Predicting the Thermal Responses and Radiopacity of Multicomponent Zinc-Silicate Glasses: A focus on ZnO, La2O3 SiO2 and TiO2, Journal of Non-Crystalline Solids 2012;358:3388-3395. 2. C V Bowen et al, Application of static dephasing regime theory to superparamagnetic iron-oxide loaded cells, Magnetic Resonance in Medicine 2002; 48:52-61.
5:27 PM
1. S. Kehoe, M. Looney, N. Kilcup, E. Tonkopi, C. Daly, R.J. Abraham, D. Boyd. J. Non-Cryst. Solids 402 (2014) 84.
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Abstract No. 171
Sorafenib loaded drug-eluting beads: loading and eluting kinetics and in vitro viability study
S.J. Lahti1,2, D. Zeng3, J.B. Jia1,2, M. Xing1,2, H.S. Kim1,2; 1 Interventional Radiology, Department of Radiology, University of Pittsburgh School of Medicine, Pittsburgh, PA; 2Interventional Oncology Translational Laboratory, Department of Radiology, University of Pittsburgh School of Medicine, Pittsburgh, PA; 3Molecular Imaging Laboratory, Department of Radiology, University of Pittsburgh School of Medicine, Pittsburgh, PA Purpose: VEGF up-regulation contributes to the reestablishment of tumor circulation and recurrence after chemoembolization, making combination chemoembolization/antiangiogenic therapy highly desirable. Sorafenib is kinase inhibitor with activity against VEGFR. In this study we demonstrate the in vitro loading, release, and biologic efficacy of sorafenib DEB. Materials and Methods: LC Beads 300-500μm (Biocompatibles UK Ltd.) microspheres were incubated with sorafenibHCl in water. Drug loading was quantified using HPLC. Drug release in normal saline was measured by UV-VIS spectrometry. Biologic efficacy was assessed by measurement of the viability of human colorectal and hepatocellular carcinoma cells in the presence or absence of sorafenib DEBs using the CellTiter-Glos Cell Viability Assay (Promega Inc.). Viability of exposed cells was calculated relative to untreated controls and expressed aspercent viability. Results: Sorafenib can be loaded and released from LC Beads. Over 48 hours, analysis of the bead supernatant showed a drop in the concentration of free sorafenib from 20 μg/ml to 0.2 μg/ml, corresponding to 98.9% loading. Upon serial replacement of the drug-depleted supernatant with fresh stock, sorafenib was loaded to at least 10mgs/mL bead, albeit with less efficiency. Under non-saturating conditions, sorafenib release in saline plateaued after 4 hours with nearly 50% being released within 1 hour. When added to HCT116 cells, sorafenib-loaded beads strongly inhibited cell growth. Relative to untreated controls, cells treated with 5 μl of sorafenib-loaded bead showed decreases in cell viability of 75.2 and 96.4% after 24 and 48 hours of exposure, respectively. In contrast, growth of the HT29 colorectal and HepG2 HCC cell lines were not significantly affected by exposure to sorafenib DEBs. Conclusion: Sorafenib can load to and release from LC Bead microspheres, and sorafenib DEBs inhibit proliferation of human colorectal cancer cells in vitro.
’
Monday
Scientific Session
Results: The use of fluoroscopy illustrated the high visibility and equivalent spatial distribution of the imageable microspheres compared to the control. Micro-CT analysis indicated that the imageable microspheres provide for excellent distribution and packing throughout the renal vasculature. Histology evaluation for all treated animals showed vessel occlusion with infarction of the embolized kidney pole without additional adverse tissue reaction. Conclusion: The imageable microspheres prepared in this study allowed immediate in vivo visual monitoring of their spatial distribution and embolization effectiveness inside target organs during the procedure. Thus, the safety and efficacy of these imageable microspheres were proven. Reference
MONDAY: Scientific Sessions
5:18 PM
Abstract No. 170
Magnetic resonance imaging characteristics of imageable embolic microspheres R. Abraham1,5, H. Basseri2, C. Davis3,4, E. Tonkopi1, S. Kehoe5, D. Boyd1,5, C. Bowen1,3; 1Diagnostic Imaging and Interventional Radiology, QEII Health Sciences Center, Halifax, NS, Canada; 2Department of Radiology, McMaster University, Hamilton, ON, Canada; 3 Biomedical Translational Imaging Center (BIOTIC), Halifax, NS, Canada; 4IWK Health Center, Halifax, NS, Canada; 5ABK Biomedical Incorporated, Halifax, NS, Canada Purpose: To evaluate magnetic resonance imaging (MRI) contrast produced by novel imageable embolic microspheres. Materials and Methods: Imageable microspheres, synthesized from a multicomponent bioglass as per Kehoe et al.1 were dispersed at varying concentrations (10, 20, 30, 40, 50% w/w, n¼5) in 8% porcine gelatin and subsequently loaded in 5mm Nuclear Magnetic Resonance (NMR) tubes. These suspensions were subjected to magnetic stirring, heating (o701C) and horizontal rotation (to prevent gravitational settling of the microspheres) prior to rapid cooling on ice to solidify the gel. Measurements of MRI susceptometry2, R2* (spectral linewidth), R2 (CPMG) and R1 (arrayed inversion recovery) were measured for all samples at room temperature using an Agilent 3T preclinical MRI. Values for pure microspheres were obtained from linear regression analysis of each parameter and extrapolation to 100% volume fraction (Vf). Results: Imageable microsphere measurements showed extrapolated pure microsphere values (100% Vf) for susceptometry (2.49 ppm), DR2* (683 s-1), DR2 (2.00 s-1) and DR1 (0.57 s-1). Negligible impact on clinical T1 or T2 scans would be expected even with 100% Vf (T1/T2 of 1.75s/500 ms for an ideal medium with infinite T1, T2). The MRI contrast mechanism for these microspheres is exclusively BMS contrast, with BMS theory2 predicting low R1, R2 enhancement, and R2* of 804 s-1*Vf (consistent with measurements of 683 s-1*Vf). These imageable microspheres may be visible (100% Vf corresponding to T2* of 1.5ms) and quantifiable (Vf¼R2*/683s-1) in vivo using high resolution R2* mapping body MRI protocols. Conclusion: The imageable microspheres studied have diamagnetic susceptibility with BMS contrast resulting in very low
JVIR
T1 and T2 contrast to confound most clinical scans with opportunity to visualize and quantify the microspheres using R2* mapping protocols. References 1. S Kehoe et al, Predicting the Thermal Responses and Radiopacity of Multicomponent Zinc-Silicate Glasses: A focus on ZnO, La2O3 SiO2 and TiO2, Journal of Non-Crystalline Solids 2012;358:3388-3395. 2. C V Bowen et al, Application of static dephasing regime theory to superparamagnetic iron-oxide loaded cells, Magnetic Resonance in Medicine 2002; 48:52-61.
5:27 PM
1. S. Kehoe, M. Looney, N. Kilcup, E. Tonkopi, C. Daly, R.J. Abraham, D. Boyd. J. Non-Cryst. Solids 402 (2014) 84.
’
Abstract No. 171
Sorafenib loaded drug-eluting beads: loading and eluting kinetics and in vitro viability study
S.J. Lahti1,2, D. Zeng3, J.B. Jia1,2, M. Xing1,2, H.S. Kim1,2; 1 Interventional Radiology, Department of Radiology, University of Pittsburgh School of Medicine, Pittsburgh, PA; 2Interventional Oncology Translational Laboratory, Department of Radiology, University of Pittsburgh School of Medicine, Pittsburgh, PA; 3Molecular Imaging Laboratory, Department of Radiology, University of Pittsburgh School of Medicine, Pittsburgh, PA Purpose: VEGF up-regulation contributes to the reestablishment of tumor circulation and recurrence after chemoembolization, making combination chemoembolization/antiangiogenic therapy highly desirable. Sorafenib is kinase inhibitor with activity against VEGFR. In this study we demonstrate the in vitro loading, release, and biologic efficacy of sorafenib DEB. Materials and Methods: LC Beads 300-500μm (Biocompatibles UK Ltd.) microspheres were incubated with sorafenibHCl in water. Drug loading was quantified using HPLC. Drug release in normal saline was measured by UV-VIS spectrometry. Biologic efficacy was assessed by measurement of the viability of human colorectal and hepatocellular carcinoma cells in the presence or absence of sorafenib DEBs using the CellTiter-Glos Cell Viability Assay (Promega Inc.). Viability of exposed cells was calculated relative to untreated controls and expressed aspercent viability. Results: Sorafenib can be loaded and released from LC Beads. Over 48 hours, analysis of the bead supernatant showed a drop in the concentration of free sorafenib from 20 μg/ml to 0.2 μg/ml, corresponding to 98.9% loading. Upon serial replacement of the drug-depleted supernatant with fresh stock, sorafenib was loaded to at least 10mgs/mL bead, albeit with less efficiency. Under non-saturating conditions, sorafenib release in saline plateaued after 4 hours with nearly 50% being released within 1 hour. When added to HCT116 cells, sorafenib-loaded beads strongly inhibited cell growth. Relative to untreated controls, cells treated with 5 μl of sorafenib-loaded bead showed decreases in cell viability of 75.2 and 96.4% after 24 and 48 hours of exposure, respectively. In contrast, growth of the HT29 colorectal and HepG2 HCC cell lines were not significantly affected by exposure to sorafenib DEBs. Conclusion: Sorafenib can load to and release from LC Bead microspheres, and sorafenib DEBs inhibit proliferation of human colorectal cancer cells in vitro.