Micro-CT Enables Microlocalisation and Quantification of Her2-targeted Gold Nanoparticles Within Tumour Regions

Overview

Journal Br J Radiol

Publisher Oxford University Press

Specialty Radiology

Date 2010 Nov 18

PMID 21081567

Citations 74

Authors

J F Hainfeld

M J OConnor

F A Dilmanian

D N Slatkin

D J Adams

H M Smilowitz

Affiliations

Soon will be listed here.

Abstract

Objectives: Gold nanoparticles are of interest as potential in vivo diagnostic and therapeutic agents, as X-ray contrast agents, drug delivery vehicles and radiation enhancers. The aim of this study was to quantitatively determine their targeting and microlocalisation in mouse tumour models after intravenous injection by using micro-CT.

Methods: Gold nanoparticles (15 nm) were coated with polyethylene glycol and covalently coupled to anti-Her2 antibodies (Herceptin). In vitro, conjugates incubated with Her2+ (BT-474) and Her2- (MCF7) human breast cancer cells showed specific targeted binding with a Her2+ to Her2- gold ratio of 39.4±2.7:1. Nude mice, simultaneously bearing subcutaneous Her2+ and Her2- human breast tumours in opposite thighs were prepared. Gold nanoparticles alone, conjugated to Herceptin or to a non-specific antibody were compared. After intravenous injection of the gold nanoparticles, gold concentrations were determined by atomic absorption spectroscopy. Microlocalisation of gold was carried out by calibrated micro-CT, giving both the radiodensities and gold concentrations in tumour and non-tumour tissue.

Results: All gold nanoparticle constructs showed accumulation, predominantly at tumour peripheries. However, the Herceptin-gold nanoparticles showed the best specific uptake in their periphery (15.8±1.7% injected dose per gram), 1.6-fold higher than Her2- tumours and 22-fold higher than surrounding muscle. Imaging readily enabled detection of small, 1.5 mm-thick tumours.

Conclusion: In this pre-clinical study, antibody-targeted 15 nm gold nanoparticles showed preferential uptake in cognate tumours, but even untargeted gold nanoparticles enhanced the visibility of tumour peripheries and enabled detection of millimetre-sized tumours. Micro-CT enabled quantification within various regions of a tumour.

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References

Paulus M, Gleason S, Kennel S, Hunsicker P, Johnson D . High resolution X-ray computed tomography: an emerging tool for small animal cancer research. Neoplasia. 2000; 2(1-2):62-70. PMC: 1531867. DOI: 10.1038/sj.neo.7900069. View

Andrew S, Johnstone R, Russell S, McKenzie I, Pietersz G . Comparison of in vitro cell binding characteristics of four monoclonal antibodies and their individual tumor localization properties in mice. Cancer Res. 1990; 50(14):4423-8. View

Lee S, Hassan M, Fisher R, Chertov O, Chernomordik V, Kramer-Marek G . Affibody molecules for in vivo characterization of HER2-positive tumors by near-infrared imaging. Clin Cancer Res. 2008; 14(12):3840-9. PMC: 3398736. DOI: 10.1158/1078-0432.CCR-07-4076. View

Hillyer J, Albrecht R . Gastrointestinal persorption and tissue distribution of differently sized colloidal gold nanoparticles. J Pharm Sci. 2001; 90(12):1927-36. DOI: 10.1002/jps.1143. View

Takeda M, Tada H, Higuchi H, Kobayashi Y, Kobayashi M, Sakurai Y . In vivo single molecular imaging and sentinel node navigation by nanotechnology for molecular targeting drug-delivery systems and tailor-made medicine. Breast Cancer. 2008; 15(2):145-52. DOI: 10.1007/s12282-008-0037-0. View

Storto G, Buchegger F, Waibel R, Kuenzi G, Offord R, Schubiger P . Biokinetics of a F(ab')3 iodine-131 labeled antigen binding construct (Mab 35) directed against CEA in patients with colorectal carcinoma. Cancer Biother Radiopharm. 2002; 16(5):371-9. DOI: 10.1089/108497801753354276. View

Hainfeld J, Slatkin D, Focella T, Smilowitz H . Gold nanoparticles: a new X-ray contrast agent. Br J Radiol. 2006; 79(939):248-53. DOI: 10.1259/bjr/13169882. View

Beatty J, Duda R, Williams L, Sheibani K, Paxton R, Beatty B . Preoperative imaging of colorectal carcinoma with 111In-labeled anticarcinoembryonic antigen monoclonal antibody. Cancer Res. 1986; 46(12 Pt 1):6494-502. View

Zhang G, Yang Z, Lu W, Zhang R, Huang Q, Tian M . Influence of anchoring ligands and particle size on the colloidal stability and in vivo biodistribution of polyethylene glycol-coated gold nanoparticles in tumor-xenografted mice. Biomaterials. 2009; 30(10):1928-36. PMC: 2745599. DOI: 10.1016/j.biomaterials.2008.12.038. View

10.

Dvorak H, Nagy J, Dvorak J, Dvorak A . Identification and characterization of the blood vessels of solid tumors that are leaky to circulating macromolecules. Am J Pathol. 1988; 133(1):95-109. PMC: 1880651. View

11.

Wise P, Barraclough C . Effects of estradiol and progesterone on plasma gonadotropins, prolactin, and LHRH in specific brain areas of ovariectomized rats. Biol Reprod. 1981; 24(4):820-30. DOI: 10.1095/biolreprod24.4.820. View

12.

Cai Q, Kim S, Choi K, Kim S, Byun S, Kim K . Colloidal gold nanoparticles as a blood-pool contrast agent for X-ray computed tomography in mice. Invest Radiol. 2007; 42(12):797-806. DOI: 10.1097/RLI.0b013e31811ecdcd. View

13.

Hainfeld J, Slatkin D, Smilowitz H . The use of gold nanoparticles to enhance radiotherapy in mice. Phys Med Biol. 2004; 49(18):N309-15. DOI: 10.1088/0031-9155/49/18/n03. View

14.

Pietras R, Fendly B, Chazin V, Pegram M, Howell S, Slamon D . Antibody to HER-2/neu receptor blocks DNA repair after cisplatin in human breast and ovarian cancer cells. Oncogene. 1994; 9(7):1829-38. View

15.

Noguchi Y, Wu J, Duncan R, Strohalm J, Ulbrich K, Akaike T . Early phase tumor accumulation of macromolecules: a great difference in clearance rate between tumor and normal tissues. Jpn J Cancer Res. 1998; 89(3):307-14. PMC: 5921799. DOI: 10.1111/j.1349-7006.1998.tb00563.x. View

16.

Terentyuk G, Maslyakova G, Suleymanova L, Khlebtsov B, Kogan B, Akchurin G . Circulation and distribution of gold nanoparticles and induced alterations of tissue morphology at intravenous particle delivery. J Biophotonics. 2009; 2(5):292-302. DOI: 10.1002/jbio.200910005. View

17.

Bhattacharyya S, Wang S, Reinecke D, Kiser Jr W, Kruger R, DeGrado T . Synthesis and evaluation of near-infrared (NIR) dye-herceptin conjugates as photoacoustic computed tomography (PCT) probes for HER2 expression in breast cancer. Bioconjug Chem. 2008; 19(6):1186-93. PMC: 2562750. DOI: 10.1021/bc700482u. View

18.

Haigler H, McKanna J, Cohen S . Direct visualization of the binding and internalization of a ferritin conjugate of epidermal growth factor in human carcinoma cells A-431. J Cell Biol. 1979; 81(2):382-95. PMC: 2110321. DOI: 10.1083/jcb.81.2.382. View

19.

Sonavane G, Tomoda K, Makino K . Biodistribution of colloidal gold nanoparticles after intravenous administration: effect of particle size. Colloids Surf B Biointerfaces. 2008; 66(2):274-80. DOI: 10.1016/j.colsurfb.2008.07.004. View

20.

Niidome T, Yamagata M, Okamoto Y, Akiyama Y, Takahashi H, Kawano T . PEG-modified gold nanorods with a stealth character for in vivo applications. J Control Release. 2006; 114(3):343-7. DOI: 10.1016/j.jconrel.2006.06.017. View