Tumor targeting with antibody-functionalized, radiolabeled carbon nanotubes Journal Article
| Authors: | McDevitt, M. R.; Chattopadhyay, D.; Kappel, B. J.; Jaggi, J. S.; Schiffman, S. R.; Antczak, C.; Njardarson, J. T.; Brentjens, R.; Scheinberg, D. A. |
| Article Title: | Tumor targeting with antibody-functionalized, radiolabeled carbon nanotubes |
| Abstract: | Single-walled carbon nanotubes (CNT) are mechanically robust graphene cylinders with a high aspect ratio that are comprised of sp2-bonded carbon atoms and possessing highly regular structures with defined periodicity. CNT exhibit unique mechanochemical properties that can be exploited for the development of novel drug delivery platforms. We hypothesized that novel prototype nanostructures consisting of biologies, radionuclides, fluorochromes, and CNT could be synthesized and designed to target tumor cells. Methods: Tumor-targeting CNT constructs were synthesized from sidewall-functionalized, water-soluble CNT platforms by covalently attaching multiple copies of tumor-specific monoclonal antibodies, radiometal-ion chelates, and fluorescent probes. The constructs were characterized spectroscopically, chromatographically, and electrophoretically. The specific reactivity of these constructs was evaluated in vitro by flow cytometry and cell-based immunoreactivity assays and in vivo using biodistribution in a murine xenograft model of lymphoma. Results: A soluble, reactive CNT platform was used as the starting point to build multifunctional constructs with appended antibody, metal-ion chelate, and fluorescent chromophore moieties to effect specific targeting, to carry and deliver a radiometal-ion, and to report location, respectively. These nanoconstructs were found to be specifically reactive with the human cancer cells they were designed to target in vivo in a model of disseminated human lymphoma and in vitro by flow cytometry and cell-based immunoreactivity assays versus appropriate controls. Conclusion: The key achievement in these studies was the selective targeting of tumor in vitro and in vivo by the use of specific antibodies appended to a soluble, nanoscale CNT construct. The ability to specifically target tumor with prototype-radiolabeled or fluorescent-labeled, antibody-appended CNT constructs was encouraging and suggested further investigation of CNT as a novel delivery platform. Copyright © 2007 by the Society of Nuclear Medicine, Inc. |
| Keywords: | controlled study; nonhuman; drug targeting; rituximab; flow cytometry; radiopharmaceuticals; mouse; animals; mice; animal tissue; fluorescence; fluorescent dye; animal experiment; animal model; cancer cell culture; tumor xenograft; mice, scid; cell line, tumor; immunoreactivity; cancer model; mice, inbred balb c; monoclonal antibody; lymphoma, b-cell; antibodies, monoclonal; indium radioisotopes; drug accumulation; drug distribution; isotope labeling; lymphoma; transplantation, heterologous; drug clearance; chemical structure; neoplasm transplantation; indium 111; antibodies, neoplasm; reaction analysis; 1,4,7,10 tetraazacyclododecane 1,4,7,10 tetraacetic acid; synthesis; chelating agents; scid mouse; nanotechnology; solubility; single walled nanotube; nanotubes, carbon; heterocyclic compounds, 1-ring; covalent bond; metal ion; dota; nanoconstructs; single-walled carbon nanotubes; metal chelate |
| Journal Title: | Journal of Nuclear Medicine |
| Volume: | 48 |
| Issue: | 7 |
| ISSN: | 0161-5505 |
| Publisher: | Society of Nuclear Medicine |
| Date Published: | 2007-07-01 |
| Start Page: | 1180 |
| End Page: | 1189 |
| Language: | English |
| DOI: | 10.2967/jnumed.106.039131 |
| PUBMED: | 17607040 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 100" - "Export Date: 17 November 2011" - "CODEN: JNMEA" - "Source: Scopus" |
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