Investigational New Drugs

, Volume 30, Issue 6, pp 2132–2140

Pretargeting of necrotic tumors with biotinylated hypericin using 123I-labeled avidin: evaluation of a two-step strategy

  • Thierry Marysael
  • Matthias Bauwens
  • Yicheng Ni
  • Guy Bormans
  • Jef Rozenski
  • Peter de Witte
PRECLINICAL STUDIES

DOI: 10.1007/s10637-011-9778-2

Cite this article as:
Marysael, T., Bauwens, M., Ni, Y. et al. Invest New Drugs (2012) 30: 2132. doi:10.1007/s10637-011-9778-2

Summary

As an alternative to directly targeting of necrotic tissue using hypericin, we synthesized a conjugate of hypericin to biotin for use in a pretargeting approach. With this conjugate, we explored the possibility of a two-step pretargeting strategy using 123I-labeled avidin as effector molecule directed against necrotic RIF-1 tumors. Hypericin was conjugated to biotin-ethylenediamine in a straightforward coupling method using n-hydroxysuccinimide and dicyclohexylcarbodiimide. The necrosis avidity of the conjugate was first confirmed in necrotic liver tissue by means of fluorescence microscopy. Using autoradiography imaging and whole body-biodistribution, the accumulation of 123I-avidin in necrotic tumor tissue was evaluated 24 h after administration and 48 h after pretargeting with hypericin-biotin. Analysis of autoradiography images show a higher accumulation of 123I-avidin in pretargeted compared to nontargeted tissue. However, absolute accumulation of 123I-avidin in necrotic tumors was low as shown by biodistribution experiments. Direct injection of hypericin-biotin or biotin-fluorescein did not substantially improve 123I-avidin accumulation after pretargeting, pointing towards a poor penetration of avidin in necrotic tissue. Our results show the feasibility of a pretargeting technique using a small molecule as targeting agent. However, for a more efficient accumulation of the effector molecule in necrotic tissue, other pretargeting strategies need to be investigated.

Keywords

Hypericin Tumor necrosis therapy Biotin Pretargeting Avidin 

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Thierry Marysael
    • 1
  • Matthias Bauwens
    • 2
  • Yicheng Ni
    • 3
  • Guy Bormans
    • 2
  • Jef Rozenski
    • 4
  • Peter de Witte
    • 1
  1. 1.Laboratorium voor Farmaceutische Biologie, Faculteit Farmaceutische WetenschappenKU LeuvenLeuvenBelgium
  2. 2.Laboratorium voor Radiofarmacie, Faculteit Farmaceutische WetenschappenK.U.LeuvenLeuvenBelgium
  3. 3.Departement Radiology, Faculteit GeneeskundeK.U.LeuvenLeuvenBelgium
  4. 4.Laboratorium voor Medicinale ChemieK.U.LeuvenLeuvenBelgium

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