99mTc-radiolabeled composites enabling in vivo imaging of arterial dispersal and retention of microspheres in the vascular network of rabbit lungs, liver, and liver tumors

Ross W Stephens,1 Gregory D Tredwell,1 Karen J Knox,1 Lee A Philip,1 David W King,1 Kelly M Debono,2 Jessica L Bell,1 Tim J Senden,1 Marcel R Tanudji,3 Jillean G Winter,3 Stephanie A Bickley,3 Michael J Tapner,3 Stephen K Jones3 1The Biomedical Radiochemistry Laboratory, Department of Applied Mathem...

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Autores principales:	Stephens RW, Tredwell GD, Knox KJ, Philip LA, King DW, Debono KM, Bell JL, Senden TJ, Tanudji MR, Winter JG, Bickley SA, Tapner MJ, Jones SK
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2019
Materias:	Liver cancer SIRT radiolabelled microspheres medical imaging Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/17d1c7ea58ba4b3190e0f3d93139d745
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spelling	oai:doaj.org-article:17d1c7ea58ba4b3190e0f3d93139d7452021-12-02T04:04:11Z99mTc-radiolabeled composites enabling in vivo imaging of arterial dispersal and retention of microspheres in the vascular network of rabbit lungs, liver, and liver tumors1178-2013https://doaj.org/article/17d1c7ea58ba4b3190e0f3d93139d7452019-01-01T00:00:00Zhttps://www.dovepress.com/99mtc-radiolabeled-composites-enabling-in-vivo-imaging-of-arterial-dis-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Ross W Stephens,1 Gregory D Tredwell,1 Karen J Knox,1 Lee A Philip,1 David W King,1 Kelly M Debono,2 Jessica L Bell,1 Tim J Senden,1 Marcel R Tanudji,3 Jillean G Winter,3 Stephanie A Bickley,3 Michael J Tapner,3 Stephen K Jones3 1The Biomedical Radiochemistry Laboratory, Department of Applied Mathematics, Research School of Physics and Engineering, Australian National University, Canberra, ACT, Australia; 2Animal Services Division, Research School of Biology, Australian National University, Canberra, ACT, Australia; 3Research and Development, Sirtex Medical Limited, Sydney, NSW, Australia Purpose: Selective internal radiation therapy (SIRT) is an effective treatment option for liver tumors, using Y-90-loaded polymer microspheres that are delivered via catheterization of the hepatic artery. Since Y-90 is a beta emitter and not conveniently imaged by standard clinical instrumentation, dosimetry is currently evaluated in each patient using a surrogate particle, 99mTechnetium-labeled macroaggregated albumin (99mTc-MAA). We report a new composite consisting of 99mTc-labeled nanoparticles attached to the same polymer microspheres as used for SIRT, which can be imaged with standard SPECT.Methods: Carbon nanoparticles with an encapsulated core of 99mTc were coated with the polycation protamine sulfate to provide electrostatic attachment to anionic polystyrene sulfonate microspheres of different sizes (30, 12, and 8 µm). The in vivo stability of these composites was determined via intravenous injection and entrapment in the capillary network of normal rabbit lungs for up to 3 hours. Furthermore, we evaluated their biodistribution in normal rabbit livers, and livers implanted with VX2 tumors, following intrahepatic artery instillation. Results: We report distribution tests for three different sizes of radiolabeled microspheres and compare the results with those obtained using 99mTc-MAA. Lung retention of the radiolabeled microspheres ranged from 72.8% to 92.9%, with the smaller diameter microspheres showing the lowest retention. Liver retention of the microspheres was higher, with retention in normal livers ranging from 99.2% to 99.8%, and in livers with VX2 tumors from 98.2% to 99.2%. The radiolabeled microspheres clearly demonstrated preferential uptake at tumor sites due to the increased arterial perfusion produced by angiogenesis.Conclusion: We describe a novel use of radiolabeled carbon nanoparticles to generate an imageable microsphere that is stable in vivo under the shear stress conditions of arterial networks. Following intra-arterial instillation in the normal rabbit liver, they distribute in a distinct segmented pattern, with the smaller microspheres extending throughout the organ in finer detail, while still being well retained within the liver. Furthermore, in livers hosting an implanted VX2 tumor, they reveal the increased arterial perfusion of tumor tissue resulting from angiogenesis. These novel composites may have potential as a more representative mimic of the vascular distribution of therapeutic microspheres in patients undergoing SIRT. Keywords: liver cancer, SIRT, radiolabeled microspheres, medical imagingStephens RWTredwell GDKnox KJPhilip LAKing DWDebono KMBell JLSenden TJTanudji MRWinter JGBickley SATapner MJJones SKDove Medical PressarticleLiver cancerSIRTradiolabelled microspheresmedical imagingMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 14, Pp 889-900 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Liver cancer SIRT radiolabelled microspheres medical imaging Medicine (General) R5-920
spellingShingle	Liver cancer SIRT radiolabelled microspheres medical imaging Medicine (General) R5-920 Stephens RW Tredwell GD Knox KJ Philip LA King DW Debono KM Bell JL Senden TJ Tanudji MR Winter JG Bickley SA Tapner MJ Jones SK 99mTc-radiolabeled composites enabling in vivo imaging of arterial dispersal and retention of microspheres in the vascular network of rabbit lungs, liver, and liver tumors
description	Ross W Stephens,1 Gregory D Tredwell,1 Karen J Knox,1 Lee A Philip,1 David W King,1 Kelly M Debono,2 Jessica L Bell,1 Tim J Senden,1 Marcel R Tanudji,3 Jillean G Winter,3 Stephanie A Bickley,3 Michael J Tapner,3 Stephen K Jones3 1The Biomedical Radiochemistry Laboratory, Department of Applied Mathematics, Research School of Physics and Engineering, Australian National University, Canberra, ACT, Australia; 2Animal Services Division, Research School of Biology, Australian National University, Canberra, ACT, Australia; 3Research and Development, Sirtex Medical Limited, Sydney, NSW, Australia Purpose: Selective internal radiation therapy (SIRT) is an effective treatment option for liver tumors, using Y-90-loaded polymer microspheres that are delivered via catheterization of the hepatic artery. Since Y-90 is a beta emitter and not conveniently imaged by standard clinical instrumentation, dosimetry is currently evaluated in each patient using a surrogate particle, 99mTechnetium-labeled macroaggregated albumin (99mTc-MAA). We report a new composite consisting of 99mTc-labeled nanoparticles attached to the same polymer microspheres as used for SIRT, which can be imaged with standard SPECT.Methods: Carbon nanoparticles with an encapsulated core of 99mTc were coated with the polycation protamine sulfate to provide electrostatic attachment to anionic polystyrene sulfonate microspheres of different sizes (30, 12, and 8 µm). The in vivo stability of these composites was determined via intravenous injection and entrapment in the capillary network of normal rabbit lungs for up to 3 hours. Furthermore, we evaluated their biodistribution in normal rabbit livers, and livers implanted with VX2 tumors, following intrahepatic artery instillation. Results: We report distribution tests for three different sizes of radiolabeled microspheres and compare the results with those obtained using 99mTc-MAA. Lung retention of the radiolabeled microspheres ranged from 72.8% to 92.9%, with the smaller diameter microspheres showing the lowest retention. Liver retention of the microspheres was higher, with retention in normal livers ranging from 99.2% to 99.8%, and in livers with VX2 tumors from 98.2% to 99.2%. The radiolabeled microspheres clearly demonstrated preferential uptake at tumor sites due to the increased arterial perfusion produced by angiogenesis.Conclusion: We describe a novel use of radiolabeled carbon nanoparticles to generate an imageable microsphere that is stable in vivo under the shear stress conditions of arterial networks. Following intra-arterial instillation in the normal rabbit liver, they distribute in a distinct segmented pattern, with the smaller microspheres extending throughout the organ in finer detail, while still being well retained within the liver. Furthermore, in livers hosting an implanted VX2 tumor, they reveal the increased arterial perfusion of tumor tissue resulting from angiogenesis. These novel composites may have potential as a more representative mimic of the vascular distribution of therapeutic microspheres in patients undergoing SIRT. Keywords: liver cancer, SIRT, radiolabeled microspheres, medical imaging
format	article
author	Stephens RW Tredwell GD Knox KJ Philip LA King DW Debono KM Bell JL Senden TJ Tanudji MR Winter JG Bickley SA Tapner MJ Jones SK
author_facet	Stephens RW Tredwell GD Knox KJ Philip LA King DW Debono KM Bell JL Senden TJ Tanudji MR Winter JG Bickley SA Tapner MJ Jones SK
author_sort	Stephens RW
title	99mTc-radiolabeled composites enabling in vivo imaging of arterial dispersal and retention of microspheres in the vascular network of rabbit lungs, liver, and liver tumors
title_short	99mTc-radiolabeled composites enabling in vivo imaging of arterial dispersal and retention of microspheres in the vascular network of rabbit lungs, liver, and liver tumors
title_full	99mTc-radiolabeled composites enabling in vivo imaging of arterial dispersal and retention of microspheres in the vascular network of rabbit lungs, liver, and liver tumors
title_fullStr	99mTc-radiolabeled composites enabling in vivo imaging of arterial dispersal and retention of microspheres in the vascular network of rabbit lungs, liver, and liver tumors
title_full_unstemmed	99mTc-radiolabeled composites enabling in vivo imaging of arterial dispersal and retention of microspheres in the vascular network of rabbit lungs, liver, and liver tumors
title_sort	99mtc-radiolabeled composites enabling in vivo imaging of arterial dispersal and retention of microspheres in the vascular network of rabbit lungs, liver, and liver tumors
publisher	Dove Medical Press
publishDate	2019
url	https://doaj.org/article/17d1c7ea58ba4b3190e0f3d93139d745
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99mTc-radiolabeled composites enabling in vivo imaging of arterial dispersal and retention of microspheres in the vascular network of rabbit lungs, liver, and liver tumors

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