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Cd125mTe/ZnS Nanoparticles coupled with anti-thrombomodulin monoclonal antibody 201B

Cd125mTe/ZnS-201B
, PhD
National Center for Biotechnology Information, NLM, NIH
Corresponding author.

Created: ; Last Update: December 24, 2009.

Chemical name:Cd125mTe/ZnS Nanoparticles coupled with anti-thrombomodulin monoclonal antibody 201B
Abbreviated name:Cd125mTe/ZnS-201B
Synonym:
Agent category:Antibody
Target:Lung thrombomodulin
Target category:Receptor
Method of detection:Single-photon emission computed tomography (SPECT), planar gamma imaging
Source of signal\contrast:125mTe
Activation:No
Studies:
  • Checkbox Rodents
Click on protein, nucleotide (RefSeq), and gene for more information about thrombomodulin.

Background

[PubMed]

Cd125mTe/ZnS nanoparticles consist of Cd125mTe cores capped with ZnS to prevent particle degradation and to reduce leaching of 125mTe (t1/2 = 58 days, x-ray = 27–30 keV, and gamma ray = 35.5 keV) into blood stream and tissues. They can be derivatized for conjugation with biomolecules, such as peptides, antibodies, nucleic acids, and small organic compounds for in vitro and in vivo studies. Cd125mTe/ZnS nanoparticles have a diameter of ~5 nm. There have been limited in vivo studies of the toxicological and pharmacological profiles of Cd125mTe/ZnS in small animals (1). Thrombomodulin (CD141 or BDCA-3) is an integral membrane receptor protein expressed on the surface of endothelial cells (2). Thrombin binds to thrombomodulin to participate in coagulation, inflammation, and cancer (3). Monoclonal antibody (mAb) 201B against mouse lung thrombomodulin has been coupled to Cd125mTe/ZnS nanoparticles for single-photon emission computed tomography (SPECT) biodistribution studies in mice (4).

Synthesis

[PubMed]

Woodward et al. (4) prepared Cd125mTe nanoparticles by incubation of 125mTe with CdO and tetradecylphosphonic acid at 250°C for 5 min. Cd125mTe nanoparticles were incubated with zinc diethydithiocarbamate in trioctylphosphine solution at 250°C for 2 h to form Cd125mTe/ZnS nanoparticles. Cd125mTe/ZnS nanoparticles were treated with excess mercaptoacetic acid at 60°C for 1 h. A reaction mixture containing 0.05 mM Cd125mTe nanoparticles, 2 nmol antibody (201B or control mAb 33), 5 mM N-hydroxysulfosuccinimide, 0.05 M 1-ethyl-3(3-dimethylaminopropyl)carbodiimide hydrochloride in phosphate-buffered saline (PBS; pH, 7.0) was incubated at room temperature for 2−4 h, then stored at 4°C overnight. Cd125mTe/ZnS-201B nanoparticles were purified with column chromatography with >97% 125mTe recovered. Cd125mTe/ZnS-201B nanoparticles retained >97% of the radioactivity after 7 days in PBS at room temperature. Kennel et al. (5) reported that Cd125mTe/ZnS-201B nanoparticles had a diameter of 20–30 nm with a radiospecific activity of 78.5 MBq/nmol (2.1 mCi/nmol of antibody). There were ~3 nanoparticles per antibody molecule.

In Vitro Studies: Testing in Cells and Tissues

[PubMed]

No publication is currently available.

Animal Studies

Rodents

[PubMed]

Woodward et al. (4) studied long-term ex vivo biodistribution in normal mice (n = 5/group) at 1, 4, 24, 72, and 144 h after intravenous injection of 2.9 MBq (0.078 mCi) Cd125mTe/ZnS-201B nanoparticles/mouse. Lung (targeted organ) accumulation was 437 ± 26, 276 ± 37, 188 ± 24, 151 ± 18, and 136 ± 19% injected dose per gram tissue (% ID/g) at the respective time points. The spleen showed accumulation of 15 ± 2, 55 ± 8, 66 ± 9, 47 ± 8, and 39 ± 12% ID/g, while the liver accumulated 15 ± 1, 25 ± 2, 23 ± 3, 18 ± 2, and 19 ± 4% ID/g at these time points. Radioactivity accumulation in the kidney was lower than in the liver.

Ex vivo biodistribution studies of Cd125mTe/ZnS nanoparticles conjugated with control mAb 33 were also performed in mice at 4 h and 24 h. Lung accumulation of Cd125mTe/ZnS nanoparticles conjugated with control mAb 33 was ~100-fold lower than that of Cd125mTe/ZnS-201B nanoparticles alone, with 4 ± 1 and 2 ± 1% ID/g at 4 h and 24 h, respectively. However, the liver accumulation was 2–3 times higher than that of Cd125mTe/ZnS-201B nanoparticles. The blood concentration was <1% ID/g for both nanoparticles at 24 h after injection.

SPECT/computed tomography imaging scans were also performed with both nanoparticles in mice. The lung, spleen, and liver were clearly visualized with 201B nanoparticles, whereas only the liver and spleen were visualized with the control mAb nanoparticles. Kennel et al. (5) confirmed and extended those data. Ex vivo autoradiography studies in the lung showed that Cd125mTe/ZnS-201B nanoparticles accumulated more uniformly and in higher quantities in the lung than Cd125mTe/ZnS nanoparticles with control mAb. Depletion of phagocytic cells in the liver prior to injection of Cd125mTe/ZnS-201B nanoparticles enhanced the accumulation in the lung and decreased accumulation in the liver with little effect on the spleen accumulation. Immunohistostaining confirmed the depletion of phagocytic cells in the liver. No blocking experiment was performed.

Other Non-Primate Mammals

[PubMed]

No publication is currently available.

Non-Human Primates

[PubMed]

No publication is currently available.

Human Studies

[PubMed]

No publication is currently available.

References

1.
Singh N., Manshian B., Jenkins G.J., Griffiths S.M., Williams P.M., Maffeis T.G., Wright C.J., Doak S.H. NanoGenotoxicology: the DNA damaging potential of engineered nanomaterials. Biomaterials. 2009;30(23-24):3891–914. [PubMed: 19427031]
2.
Koutsi A., Papapanagiotou A., Papavassiliou A.G. Thrombomodulin: from haemostasis to inflammation and tumourigenesis. Int J Biochem Cell Biol. 2008;40(9):1669–73. [PubMed: 17709273]
3.
Hanly A.M., Winter D.C. The role of thrombomodulin in malignancy. Semin Thromb Hemost. 2007;33(7):673–9. [PubMed: 18000794]
4.
Woodward D., Kennel S.J., Mirzadeh S., Dai S. W. J.S., and R. T., In vivo SPECT/CT imaging and biodistribution using radioactive Cd125mTe/ZnD nanoparticles. Nanotechnology. 2007;18:1–5.
5.
Kennel S.J., Woodward J.D., Rondinone A.J., Wall J., Huang Y., Mirzadeh S. The fate of MAb-targeted Cd(125m)Te/ZnS nanoparticles in vivo. Nucl Med Biol. 2008;35(4):501–14. [PubMed: 18482688]

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