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Abstract No. 192: MRI-guided transcatheter delivery of spio-labeled natural killer cells to hepatocellular carcinoma
JVIR 䡲 Scientific Session
Tuesday 䡲 S79
Purpose: High Intensity Focused Ultrasound (HIFU) is a completely non-invasive thermal ablation technique. Whereas most of the nerve block techniques are at the most minimally invasive and hence carry greater risk of complications. The objective of our study is to investigate if HIFU could non-invasively produce nerve conduction block. This can potentially be used to treat conditions like neuropathic pain and spasticity. Materials and Methods: Acute HIFU ablation lesions were created in bilateral sciatic nerves of swine model (Yorkshire pigs, n⫽5) for histo-pathological evaluation. HIFU lesions were created in bilateral sciatic nerves under magnetic resonance (MR) guidance. Animals were then immediately euthanized. Post euthanasia necropsy was performed and the tissue samples were collected for histopathological analysis and transmission electron microscopic examination for ultrastructural changes of the nerves. Results: Acute HIFU nerve lesions showed evidence of well demarcated, focally extensive thermal necrosis, on gross and histological examination. This was characterized by nuclear pyknosis, hyalinization and basophilia of stroma (endoneurium, perineurium and epineurium), along with hyperemia. Small multifocal hemorrhages were seen in the adjacent fat plan between the nerve and muscle with also edema and necrosis of the adjacent muscle. On transmission electron microscopic examination the regular smooth spirally oriented myelin seen in the normal nerve (control), was seen to be replaced by interrupted irregular wavy myelin sheath separated by multiple electron lucent and elongated vacuolar spaces within. Also the axoplasm showed focally disrupted pattern. Conclusion: This study demonstrates the feasibility of HIFU as a noninvasive nerve block technique. Future studies are necessary to evaluate the accurate targeting, reversibility and clinical significance.
1:38 PM
Interventional Oncology: Radioembolization II Tuesday, March 27, 2012 1:30 PM – 3:30 PM Room: 122 1:30 PM
Abstract No. 192
MRI-guided transcatheter delivery of spio-labeled natural killer cells to hepatocellular carcinoma 1
1
1
1,2
A. Sheu , Z. Zhang , W. Li , R.A. Omary , A.C. Larson1,2; 1Radiology, Northwestern University Feinberg School of Medicine, Chicago, IL; 2Biomedical Engineering, Northwestern University - McCormick School of Engineering and Applied Science, Evanston, IL Purpose: Adoptive immunotherapy with natural killer (NK) lymphocytes is a promising approach for treatment of HCC; however, IV delivery may lead to insufficient NK dose in tumors. Quantification of intra-tumoral NK delivery may be crucial to
Abstract No. 193
Assessment of holmium-166 microsphere biodistribution after radioembolization in patients with liver metastases: comparison between MRI and SPECT M. Smits1, G. van de Maat2, M. Elschot1, M.A. Vente1, M. Lam1, P. Seevinck2, F. van het Schip1, B. Zonnenberg1,3, C.J. Bakker2, H. de Jong1, M. van den Bosch1, F. Nijsen1; 1Radiology, University Medical Center Utrecht, Utrecht, Netherlands; 2Image Sciences Institute, University Medical Center Utrecht, Utrecht, Netherlands; 3Internal Medicine, University Medical Center Utrecht, Utrecht, Netherlands Purpose: Holmium-166 poly (L-lactic acid) microspheres (166HoPLLA-MS) have been developed as an alternative to yttrium-90 MS for radioembolization (RE). 166Ho-RE is currently under investigation in a phase I trial (HEPAR trial, ClinicalTrials.gov Identifier: NCT01031784). The main advantage of 166HoPLLA-MS is that it provides the possibility for in vivo biodistribution assessment post therapy by means of both MRI and SPECT. The purpose of this study was to validate MR-based assessment of the intrahepatic biodistribution of 166Ho-PLLA-MS with SPECT as a reference standard. Materials and Methods: 5 patients with liver metastases were treated by 166Ho-radioembolization (mean administered activity
TUESDAY: Scientific Sessions
Scientific Session 15
optimize therapy or to predict response. The purpose of this study was: a) to demonstrate the feasibility of transcatheter intra-arterial (IA) infusion for targeted delivery to HCC and b) to validate the potential of iron-oxide labeling methods to visualize IA NK delivery with MRI. Materials and Methods: NK-92 cells (ATCC; Manassas, VA) were labeled with iron-oxide nanoparticles (GENOVIS AB, Sweden) using a protamine transfection agent. Cell viability was measured using a cell counter, and labeling efficacy was measured by fluorescence microscopy. McA-RH7777 liver tumors were grown in 6 Sprague-Dawley rats. GDA was ligated distal to site of puncture, 24G catheter was placed in the proper hepatic artery, and the celiac artery was temporarily ligated to control bleeding. DSA confirmed catheter placement. 7.0T MRI scanner (Bruker, Billerica, MA) performed T2W and T2*W scans pre- and postNK infusion. T2* measurements in tumor and normal liver were compared pre- and post-infusion using paired t-test. Livers were harvested for Prussian blue histology to confirm NK delivery; percentage of cells in a high-powered (20⫻) field identified as NK (%HPF) were compared between tumor and normal tissues. Results: NK cell viability was ⬎90% before and after labeling. Labeling efficacy was ⬎95%. DSA confirmed successful catheter placement in each animal. Transcatheter NK infusions led to significant reductions in tumor T2* (mean ⫾ SD: pre 13.5⫾0.2ms, post 6.4⫾2.6ms, p⫽0.02) during intra-procedural MRI scans. NK deposition attenuated tissue signal intensity within both T2 and T2* scans. Histologic %HPF measurements were significantly higher in tumor (0.81%) than surrounding normal liver tissues (0.08%) (p⬍0.01). Conclusion: Transcatheter infusion permitted selective delivery of NK cells to HCC. The intra-hepatic distribution of iron-oxide labeled NK cells was quantitatively visualized with MRI. Future studies will compare therapeutic outcomes following IV and transcatheter IA administration routes.
Tuesday 䡲 S79
Purpose: High Intensity Focused Ultrasound (HIFU) is a completely non-invasive thermal ablation technique. Whereas most of the nerve block techniques are at the most minimally invasive and hence carry greater risk of complications. The objective of our study is to investigate if HIFU could non-invasively produce nerve conduction block. This can potentially be used to treat conditions like neuropathic pain and spasticity. Materials and Methods: Acute HIFU ablation lesions were created in bilateral sciatic nerves of swine model (Yorkshire pigs, n⫽5) for histo-pathological evaluation. HIFU lesions were created in bilateral sciatic nerves under magnetic resonance (MR) guidance. Animals were then immediately euthanized. Post euthanasia necropsy was performed and the tissue samples were collected for histopathological analysis and transmission electron microscopic examination for ultrastructural changes of the nerves. Results: Acute HIFU nerve lesions showed evidence of well demarcated, focally extensive thermal necrosis, on gross and histological examination. This was characterized by nuclear pyknosis, hyalinization and basophilia of stroma (endoneurium, perineurium and epineurium), along with hyperemia. Small multifocal hemorrhages were seen in the adjacent fat plan between the nerve and muscle with also edema and necrosis of the adjacent muscle. On transmission electron microscopic examination the regular smooth spirally oriented myelin seen in the normal nerve (control), was seen to be replaced by interrupted irregular wavy myelin sheath separated by multiple electron lucent and elongated vacuolar spaces within. Also the axoplasm showed focally disrupted pattern. Conclusion: This study demonstrates the feasibility of HIFU as a noninvasive nerve block technique. Future studies are necessary to evaluate the accurate targeting, reversibility and clinical significance.
1:38 PM
Interventional Oncology: Radioembolization II Tuesday, March 27, 2012 1:30 PM – 3:30 PM Room: 122 1:30 PM
Abstract No. 192
MRI-guided transcatheter delivery of spio-labeled natural killer cells to hepatocellular carcinoma 1
1
1
1,2
A. Sheu , Z. Zhang , W. Li , R.A. Omary , A.C. Larson1,2; 1Radiology, Northwestern University Feinberg School of Medicine, Chicago, IL; 2Biomedical Engineering, Northwestern University - McCormick School of Engineering and Applied Science, Evanston, IL Purpose: Adoptive immunotherapy with natural killer (NK) lymphocytes is a promising approach for treatment of HCC; however, IV delivery may lead to insufficient NK dose in tumors. Quantification of intra-tumoral NK delivery may be crucial to
Abstract No. 193
Assessment of holmium-166 microsphere biodistribution after radioembolization in patients with liver metastases: comparison between MRI and SPECT M. Smits1, G. van de Maat2, M. Elschot1, M.A. Vente1, M. Lam1, P. Seevinck2, F. van het Schip1, B. Zonnenberg1,3, C.J. Bakker2, H. de Jong1, M. van den Bosch1, F. Nijsen1; 1Radiology, University Medical Center Utrecht, Utrecht, Netherlands; 2Image Sciences Institute, University Medical Center Utrecht, Utrecht, Netherlands; 3Internal Medicine, University Medical Center Utrecht, Utrecht, Netherlands Purpose: Holmium-166 poly (L-lactic acid) microspheres (166HoPLLA-MS) have been developed as an alternative to yttrium-90 MS for radioembolization (RE). 166Ho-RE is currently under investigation in a phase I trial (HEPAR trial, ClinicalTrials.gov Identifier: NCT01031784). The main advantage of 166HoPLLA-MS is that it provides the possibility for in vivo biodistribution assessment post therapy by means of both MRI and SPECT. The purpose of this study was to validate MR-based assessment of the intrahepatic biodistribution of 166Ho-PLLA-MS with SPECT as a reference standard. Materials and Methods: 5 patients with liver metastases were treated by 166Ho-radioembolization (mean administered activity
TUESDAY: Scientific Sessions
Scientific Session 15
optimize therapy or to predict response. The purpose of this study was: a) to demonstrate the feasibility of transcatheter intra-arterial (IA) infusion for targeted delivery to HCC and b) to validate the potential of iron-oxide labeling methods to visualize IA NK delivery with MRI. Materials and Methods: NK-92 cells (ATCC; Manassas, VA) were labeled with iron-oxide nanoparticles (GENOVIS AB, Sweden) using a protamine transfection agent. Cell viability was measured using a cell counter, and labeling efficacy was measured by fluorescence microscopy. McA-RH7777 liver tumors were grown in 6 Sprague-Dawley rats. GDA was ligated distal to site of puncture, 24G catheter was placed in the proper hepatic artery, and the celiac artery was temporarily ligated to control bleeding. DSA confirmed catheter placement. 7.0T MRI scanner (Bruker, Billerica, MA) performed T2W and T2*W scans pre- and postNK infusion. T2* measurements in tumor and normal liver were compared pre- and post-infusion using paired t-test. Livers were harvested for Prussian blue histology to confirm NK delivery; percentage of cells in a high-powered (20⫻) field identified as NK (%HPF) were compared between tumor and normal tissues. Results: NK cell viability was ⬎90% before and after labeling. Labeling efficacy was ⬎95%. DSA confirmed successful catheter placement in each animal. Transcatheter NK infusions led to significant reductions in tumor T2* (mean ⫾ SD: pre 13.5⫾0.2ms, post 6.4⫾2.6ms, p⫽0.02) during intra-procedural MRI scans. NK deposition attenuated tissue signal intensity within both T2 and T2* scans. Histologic %HPF measurements were significantly higher in tumor (0.81%) than surrounding normal liver tissues (0.08%) (p⬍0.01). Conclusion: Transcatheter infusion permitted selective delivery of NK cells to HCC. The intra-hepatic distribution of iron-oxide labeled NK cells was quantitatively visualized with MRI. Future studies will compare therapeutic outcomes following IV and transcatheter IA administration routes.