A ferritin-containing nanoconjugate as MRI image-guidance to target Necl-5, a tumor-surface antigen: a potential thermal accelerant for microwave ablation

Purpose: A ferritin-containing nanoparticle conjugated with a target-specific antibody was investigated as a MRI contrast agent for tumor detection. A genetically modified ferritin to markedly improve Fe (III) payload (up to 7,000 Fe ions), was chemically tethered to a monoclonal antibody against ra...

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Main Authors: Park, William K. C., Mills, David R., Lim, Sierin, Sana, Barindra, Frank, Victoria E., Kenyon, Brendan M., Primmer, Michael P., Paul, Jarod B., Baird, Greyson L., Walsh, Edward G., Dupuy, Damian E.
Other Authors: Ryan, Thomas P.
Format: Conference or Workshop Item
Language:English
Published: 2018
Subjects:
Online Access:https://hdl.handle.net/10356/86825
http://hdl.handle.net/10220/44303
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Institution: Nanyang Technological University
Language: English
id sg-ntu-dr.10356-86825
record_format dspace
institution Nanyang Technological University
building NTU Library
continent Asia
country Singapore
Singapore
content_provider NTU Library
collection DR-NTU
language English
topic Ferritin
Nanoconjugate
spellingShingle Ferritin
Nanoconjugate
Park, William K. C.
Mills, David R.
Lim, Sierin
Sana, Barindra
Frank, Victoria E.
Kenyon, Brendan M.
Primmer, Michael P.
Paul, Jarod B.
Baird, Greyson L.
Walsh, Edward G.
Dupuy, Damian E.
A ferritin-containing nanoconjugate as MRI image-guidance to target Necl-5, a tumor-surface antigen: a potential thermal accelerant for microwave ablation
description Purpose: A ferritin-containing nanoparticle conjugated with a target-specific antibody was investigated as a MRI contrast agent for tumor detection. A genetically modified ferritin to markedly improve Fe (III) payload (up to 7,000 Fe ions), was chemically tethered to a monoclonal antibody against rat Nectin-like molecule 5 (Necl-5). Necl-5 is a cell surface glycoprotein that is highly expressed on the cell surface of many common epithelial cancers, including prostate cancer. It was previously demonstrated that this novel nanoconjugate agent exhibited effective in vitro targeting of Necl- 5 expressing tumor cells and exhibited strong MRI contrast characteristics via shortening of T2. Here, we demonstrate that the nanoconjugate-Necl-5 interaction can be exploited to target and detect tumor in vivo by MRI. Procedure: Using an in vivo tumor model (i.e., tumor size 0.5-1 cm, immunodeficient beige/nude/xid mouse, xenograft injection with transformed rat prostate cells), efficacy of the conjugate targeting the tumor was examined. We used two injection strategies, a direct and a tail vein injection (0.8 mg, 300 μL per subject). Pre-injection baseline and postinjection scans were performed with the following spin-echo sequence parameters: Field of view = 90x53mm, reconstruction matrix size = 192x114, slice thickness = 1mm (10 slices), repetition time (TR) = 2070 ms, echo times (TE) = 11-198 ms in 11ms steps (18 echoes), number of averages = 2, acquisition time per scan = 7min 56s. Results: All T2 data obtained were converted to R2 for demonstration purposes (R2 = 1/T2). The tail vein injected conjugate significantly increased R2 response (22.9 ± 5.2 s-1) as compared to control (13.5 ±1.7 s-1) at 4 h. The weaker R2 increase was noted (15.2 ± 2.0 s-1) at 24 h. No notable changes in R2 were observed in surrounding tissues regardless the stages of the measurement. We also measured the initial conjugate kinetics for both injection methods with respect to the ability of targeting the tumor. Direct injection of the nanoconjugate in to the center of the tumor showed a stronger and more rapid increase in R2 than the tail vein injection. Conclusion: The nanoconjugate interacts strongly and selectively in situ with Necl-5 overexpressing tumor cells. Direct injection of the nanoconjugate into the body of the tumor caused a more significant in situ R2 increase in MRI than the tail vein injection. Varying degrees of R2 increase within the tumor mass is likely to represent different distribution patterns of the conjugate, reflective of tumor heterogeneity.
author2 Ryan, Thomas P.
author_facet Ryan, Thomas P.
Park, William K. C.
Mills, David R.
Lim, Sierin
Sana, Barindra
Frank, Victoria E.
Kenyon, Brendan M.
Primmer, Michael P.
Paul, Jarod B.
Baird, Greyson L.
Walsh, Edward G.
Dupuy, Damian E.
format Conference or Workshop Item
author Park, William K. C.
Mills, David R.
Lim, Sierin
Sana, Barindra
Frank, Victoria E.
Kenyon, Brendan M.
Primmer, Michael P.
Paul, Jarod B.
Baird, Greyson L.
Walsh, Edward G.
Dupuy, Damian E.
author_sort Park, William K. C.
title A ferritin-containing nanoconjugate as MRI image-guidance to target Necl-5, a tumor-surface antigen: a potential thermal accelerant for microwave ablation
title_short A ferritin-containing nanoconjugate as MRI image-guidance to target Necl-5, a tumor-surface antigen: a potential thermal accelerant for microwave ablation
title_full A ferritin-containing nanoconjugate as MRI image-guidance to target Necl-5, a tumor-surface antigen: a potential thermal accelerant for microwave ablation
title_fullStr A ferritin-containing nanoconjugate as MRI image-guidance to target Necl-5, a tumor-surface antigen: a potential thermal accelerant for microwave ablation
title_full_unstemmed A ferritin-containing nanoconjugate as MRI image-guidance to target Necl-5, a tumor-surface antigen: a potential thermal accelerant for microwave ablation
title_sort ferritin-containing nanoconjugate as mri image-guidance to target necl-5, a tumor-surface antigen: a potential thermal accelerant for microwave ablation
publishDate 2018
url https://hdl.handle.net/10356/86825
http://hdl.handle.net/10220/44303
_version_ 1787136698917847040
spelling sg-ntu-dr.10356-868252023-12-29T06:44:10Z A ferritin-containing nanoconjugate as MRI image-guidance to target Necl-5, a tumor-surface antigen: a potential thermal accelerant for microwave ablation Park, William K. C. Mills, David R. Lim, Sierin Sana, Barindra Frank, Victoria E. Kenyon, Brendan M. Primmer, Michael P. Paul, Jarod B. Baird, Greyson L. Walsh, Edward G. Dupuy, Damian E. Ryan, Thomas P. School of Chemical and Biomedical Engineering Proceedings of SPIE - Energy-based Treatment of Tissue and Assessment IX Ferritin Nanoconjugate Purpose: A ferritin-containing nanoparticle conjugated with a target-specific antibody was investigated as a MRI contrast agent for tumor detection. A genetically modified ferritin to markedly improve Fe (III) payload (up to 7,000 Fe ions), was chemically tethered to a monoclonal antibody against rat Nectin-like molecule 5 (Necl-5). Necl-5 is a cell surface glycoprotein that is highly expressed on the cell surface of many common epithelial cancers, including prostate cancer. It was previously demonstrated that this novel nanoconjugate agent exhibited effective in vitro targeting of Necl- 5 expressing tumor cells and exhibited strong MRI contrast characteristics via shortening of T2. Here, we demonstrate that the nanoconjugate-Necl-5 interaction can be exploited to target and detect tumor in vivo by MRI. Procedure: Using an in vivo tumor model (i.e., tumor size 0.5-1 cm, immunodeficient beige/nude/xid mouse, xenograft injection with transformed rat prostate cells), efficacy of the conjugate targeting the tumor was examined. We used two injection strategies, a direct and a tail vein injection (0.8 mg, 300 μL per subject). Pre-injection baseline and postinjection scans were performed with the following spin-echo sequence parameters: Field of view = 90x53mm, reconstruction matrix size = 192x114, slice thickness = 1mm (10 slices), repetition time (TR) = 2070 ms, echo times (TE) = 11-198 ms in 11ms steps (18 echoes), number of averages = 2, acquisition time per scan = 7min 56s. Results: All T2 data obtained were converted to R2 for demonstration purposes (R2 = 1/T2). The tail vein injected conjugate significantly increased R2 response (22.9 ± 5.2 s-1) as compared to control (13.5 ±1.7 s-1) at 4 h. The weaker R2 increase was noted (15.2 ± 2.0 s-1) at 24 h. No notable changes in R2 were observed in surrounding tissues regardless the stages of the measurement. We also measured the initial conjugate kinetics for both injection methods with respect to the ability of targeting the tumor. Direct injection of the nanoconjugate in to the center of the tumor showed a stronger and more rapid increase in R2 than the tail vein injection. Conclusion: The nanoconjugate interacts strongly and selectively in situ with Necl-5 overexpressing tumor cells. Direct injection of the nanoconjugate into the body of the tumor caused a more significant in situ R2 increase in MRI than the tail vein injection. Varying degrees of R2 increase within the tumor mass is likely to represent different distribution patterns of the conjugate, reflective of tumor heterogeneity. Published version 2018-01-10T06:23:05Z 2019-12-06T16:29:42Z 2018-01-10T06:23:05Z 2019-12-06T16:29:42Z 2017 Conference Paper Park, W. K. C., Mills, D. R., Lim, S., Sana, B., Frank, V. E., Kenyon, B. M., et al. (2017). A ferritin-containing nanoconjugate as MRI image-guidance to target Necl-5, a tumor-surface antigen: a potential thermal accelerant for microwave ablation. Proceedings of SPIE - Energy-based Treatment of Tissue and Assessment IX, 10066, 100660H-. https://hdl.handle.net/10356/86825 http://hdl.handle.net/10220/44303 10.1117/12.2250041 en © 2017 Society of Photo-Optical Instrumentation Engineers (SPIE). This paper was published in Proceedings of SPIE - Energy-based Treatment of Tissue and Assessment IX and is made available as an electronic reprint (preprint) with permission of Society of Photo-Optical Instrumentation Engineers (SPIE). The published version is available at: [http://dx.doi.org/10.1117/12.2250041]. One print or electronic copy may be made for personal use only. Systematic or multiple reproduction, distribution to multiple locations via electronic or other means, duplication of any material in this paper for a fee or for commercial purposes, or modification of the content of the paper is prohibited and is subject to penalties under law. 9 p. application/pdf