Skip to main content
SpringerLink
Log in

Radiosynthesis and Assessment of Ocular Pharmacokinetics of 124I-Labeled Chitosan in Rabbits Using Small-Animal PET

  • Brief Article
  • Published:
Molecular Imaging and Biology Aims and scope Submit manuscript

Abstract

Purpose

The polysaccharide chitosan is a unique material for the design of ocular drug-delivery vehicles. The aim of this study was to radiolabel chitosan with iodine-124 (124I) for measurement of ocular pharmacokinetics in rabbits using small-animal positron emission tomography (PET).

Procedures

Crl:CHBB (HM) rabbits received one drop (35 µL) of either a formulation containing chitosan (0.5%, w/v) spiked with 124I-labeled chitosan ([124I]chitosan) (n = 4) or a control solution of sodium [124I]iodide in buffer (n = 2) in the conjunctival sac of the right eye. Radioactivity distribution in the head region was measured at five different time points between 0 and 22 h after topical application. Regions of interest were manually defined in the reconstructed PET images, and activity concentration was quantified as percent applied dose (AD) per cubic centimeter tissue.

Results

Clear differences were observed in the ocular pharmacokinetics of the two formulations. At 3 h after application, ocular activity uptake was 0.5 ± 0.1%AD/cc for sodium [124I]iodide, compared to 4.7 ± 5.3%AD/cc for the [124I]chitosan formulation.

Conclusions

We were able to show that ocular pharmacokinetics of 124I-labeled ophthalmic formulations can be measured with small-animal PET and that [124I]chitosan had approximately a 2-fold increased ocular retention through the study period compared to sodium [124I]iodide.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1.
Fig. 2.
Fig. 3.

References

  1. Illum L (1998) Chitosan and its use as a pharmaceutical excipient. Pharm Res 15:1326–1331

    Article  PubMed  CAS  Google Scholar 

  2. Alonso MJ, Sanchez A (2003) The potential of chitosan in ocular drug delivery. J Pharm Pharmacol 55:1451–1463

    Article  PubMed  CAS  Google Scholar 

  3. Felt O, Furrer P, Mayer JM et al (1999) Topical use of chitosan in ophthalmology: tolerance assessment and evaluation of precorneal retention. Int J Pharm 180:185–193

    Article  PubMed  CAS  Google Scholar 

  4. Felt O, Carrel A, Baehni P, Buri P, Gurny R (2000) Chitosan as tear substitute: a wetting agent endowed with antimicrobial efficacy. J Ocul Pharmacol Ther 16:261–270

    Article  PubMed  CAS  Google Scholar 

  5. Bernkop-Schnürch A, Hornof M, Guggi D (2004) Thiolated chitosans. Eur J Pharm Biopharm 57:9–17

    Article  PubMed  Google Scholar 

  6. Leitner VM, Walker GF, Bernkop-Schnürch A (2003) Thiolated polymers: evidence for the formation of disulphide bonds with mucus glycoproteins. Eur J Pharm Biopharm 56:207–214

    Article  PubMed  CAS  Google Scholar 

  7. Hongyok T, Chae JJ, Shin YJ et al (2009) Effect of chitosan-N-acetylcysteine conjugate in a mouse model of botulinum toxin B-induced dry eye. Arch Ophthalmol 127:525–532

    Article  PubMed  CAS  Google Scholar 

  8. Gupta H, Aqil M, Khar RK et al (2009) Development and characterization of 99mTc-timolol maleate for evaluating efficacy of in situ ocular drug delivery system. AAPS PharmSciTech 10:540–546

    Article  PubMed  CAS  Google Scholar 

  9. Soane RJ, Frier M, Perkins AC et al (1999) Evaluation of the clearance characteristics of bioadhesive systems in humans. Int J Pharm 178:55–65

    Article  PubMed  CAS  Google Scholar 

  10. Loening AM, Gambhir SS (2003) AMIDE: a free software tool for multimodality medical image analysis. Mol Imaging 2:131–137

    Article  PubMed  Google Scholar 

  11. Wilbur DS (1992) Radiohalogenation of proteins: an overview of radionuclides, labeling methods, and reagents for conjugate labeling. Bioconjug Chem 3:433–470

    Article  PubMed  CAS  Google Scholar 

  12. Bolton AE, Hunter WM (1973) The labelling of proteins to high specific radioactivities by conjugation to a 125I-containing acylating agent. Biochem J 133:529–539

    PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The authors thank Gloria Stundner (AIT Austrian Institute of Technology GmbH) and Thomas Filip and Maria Zsebedics (Seibersdorf Laboratories GmbH) for their skilful help with laboratory animal handling and the staff of the radiochemistry laboratory (Seibersdorf Laboratories GmbH) for performing the radiolabeling. Peter Angelberger is gratefully acknowledged for continuous support and critical reading of the manuscript. AIT Austrian Institute of Technology GmbH received research funding from Croma Pharma GmbH for conducting the present study. Croma Pharma GmbH had access to all data and reviewed the manuscript. Drs Dangl, Hoffer, and Hornof are Croma Pharma GmbH employees. The other authors declare no conflict of interest.

Author information

Authors and Affiliations

  1. Molecular Medicine, AIT Austrian Institute of Technology GmbH, 2444, Seibersdorf, Austria

    Claudia Kuntner, Thomas Wanek & Oliver Langer

  2. Research Department, Croma Pharma GmbH, 2100, Leobendorf, Austria

    Martin Hoffer, Daniel Dangl & Margit Hornof

  3. Radiopharmaceuticals, Radiation Safety and Applications, Seibersdorf Labor GmbH, Seibersdorf, Austria

    Herbert Kvaternik

  4. Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria

    Oliver Langer

Authors
  1. Claudia Kuntner
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Thomas Wanek
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Martin Hoffer
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Daniel Dangl
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Margit Hornof
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Herbert Kvaternik
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Oliver Langer
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Claudia Kuntner.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kuntner, C., Wanek, T., Hoffer, M. et al. Radiosynthesis and Assessment of Ocular Pharmacokinetics of 124I-Labeled Chitosan in Rabbits Using Small-Animal PET. Mol Imaging Biol 13, 222–226 (2011). https://doi.org/10.1007/s11307-010-0352-7

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11307-010-0352-7

Key words

Search

Navigation