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01-12-2012 | PRECLINICAL STUDIES

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

Authors: Thierry Marysael, Matthias Bauwens, Yicheng Ni, Guy Bormans, Jef Rozenski, Peter de Witte

Published in: Investigational New Drugs | Issue 6/2012

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.

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Title: Pretargeting of necrotic tumors with biotinylated hypericin using 123I-labeled avidin: evaluation of a two-step strategy
Authors: Thierry Marysael
Matthias Bauwens
Yicheng Ni
Guy Bormans
Jef Rozenski
Peter de Witte
Publication date: 01-12-2012
Publisher: Springer US
Published in: Investigational New Drugs / Issue 6/2012
Print ISSN: 0167-6997
Electronic ISSN: 1573-0646
DOI: https://doi.org/10.1007/s10637-011-9778-2

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