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Title: Pretargeting of necrotic tumors with biotinylated hypericin using I-123-labeled avidin: evaluation of a two-step strategy
Authors: Marysael, Thierry ×
Bauwens, Matthias
Ni, Yicheng
Bormans, Guy
Rozenski, Jef
de Witte, Peter #
Issue Date: Dec-2012
Publisher: M. Nijhoff
Series Title: Investigational New Drugs vol:30 issue:6 pages:2132-2140
Abstract: 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 (123)I-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 (123)I-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 (123)I-avidin in pretargeted compared to nontargeted tissue. However, absolute accumulation of (123)I-avidin in necrotic tumors was low as shown by biodistribution experiments. Direct injection of hypericin-biotin or biotin-fluorescein did not substantially improve (123)I-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.
URI: 
ISSN: 0167-6997
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Medicinal Chemistry (Rega Institute)
Laboratory for Pharmaceutical Biology (-)
Radiology
Radiopharmacy
Theragnostic Laboratory (+)
× corresponding author
# (joint) last author

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