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Proceedings Paper

A ferritin-containing nanoconjugate as MRI image-guidance to target Necl-5, a tumor-surface antigen: a potential thermal accelerant for microwave ablation
Author(s): William K. C. Park; David R. Mills; Sierin Lim; Barindra Sana; Victoria E. Frank; Brendan M. Kenyon; Michael P. Primmer; Jarod B. Paul; Greyson L. Baird; Edward Walsh; Damian E. Dupuy
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Paper Abstract

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.

Paper Details

Date Published: 22 February 2017
PDF: 9 pages
Proc. SPIE 10066, Energy-based Treatment of Tissue and Assessment IX, 100660H (22 February 2017); doi: 10.1117/12.2250041
Show Author Affiliations
William K. C. Park, Rhode Island Hospital (United States)
The Warren Alpert Medical School of Brown Univ. (United States)
David R. Mills, Rhode Island Hospital (United States)
The Warren Alpert Medical School of Brown Univ. (United States)
Sierin Lim, Nanyang Technological Univ. (Singapore)
Barindra Sana, Nanyang Technological Univ. (Singapore)
Victoria E. Frank, Rhode Island Hospital (United States)
The Warren Alpert Medical School of Brown Univ. (United States)
Brendan M. Kenyon, Rhode Island Hospital (United States)
The Warren Alpert Medical School of Brown Univ. (United States)
Michael P. Primmer, Rhode Island Hospital (United States)
The Warren Alpert Medical School of Brown Univ. (United States)
Jarod B. Paul, Rhode Island Hospital (United States)
The Warren Alpert Medical School of Brown Univ. (United States)
Greyson L. Baird, Rhode Island Hospital (United States)
The Warren Alpert Medical School of Brown Univ. (United States)
Edward Walsh, Brown Univ. Institute for Brain Science (United States)
Damian E. Dupuy, Rhode Island Hospital (United States)
The Warren Alpert Medical School of Brown Univ. (United States)


Published in SPIE Proceedings Vol. 10066:
Energy-based Treatment of Tissue and Assessment IX
Thomas P. Ryan, Editor(s)

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