MBP-annexin V radiolabeled directly with iodine-124 can be used to image apoptosis in vivo using PET.

2.50
Hdl Handle:
http://hdl.handle.net/10541/76835
Title:
MBP-annexin V radiolabeled directly with iodine-124 can be used to image apoptosis in vivo using PET.
Authors:
Dekker, Bronwen A; Keen, Heather G; Lyons, Steve; Disley, Lynn; Hastings, David L; Reader, Andrew J; Ottewell, Penny; Watson, Alastair; Zweit, Jamal
Abstract:
A noninvasive method of measuring programmed cell death in the tumors of cancer patients using positron-emission tomography (PET) would provide valuable information regarding their response to therapeutic intervention. Our strategy is to radiolabel annexin V, a protein that binds to phosphatidylserine moieties that are translocated to the external leaflet of plasma membranes during apoptosis. We developed a phosphatidylserine-ELISA capable of distinguishing wild type from point mutant annexin V that is known to have a lower phosphatidylserine binding affinity. A maltose-binding protein/annexin V chimera was synthesized and purified with high yield using amylose resin. We showed that it bound to phosphatidylserine in the ELISA as well as to that exposed on apoptotic Jurkat cells; therefore, it was used in the development of a method for radiolabeling annexin V using iodine radionuclides. MBP-annexin V retained its phosphatidylserine binding properties on direct iodination, but at high levels of oxidizing agents (iodogen and chloramine T), its specificity for phosphatidylserine was compromised. (124)I-MBP-annexin V was successfully used to image Fas-mediated hepatic cell death in BDF-1 mice using PET. In conclusion, we have shown that MBP-annexin V and the phosphatidylserine ELISA are useful tools for the development of methods for radiolabeling annexin V for PET imaging.
Affiliation:
Cancer Research UK/UMIST, Department of Radiochemical Targeting and Imaging, Paterson Institute for Cancer Research, M20 4BX Manchester, UK.
Citation:
MBP-annexin V radiolabeled directly with iodine-124 can be used to image apoptosis in vivo using PET. 2005, 32 (3):241-52 Nucl. Med. Biol.
Journal:
Nuclear Medicine and Biology
Issue Date:
Apr-2005
URI:
http://hdl.handle.net/10541/76835
DOI:
10.1016/j.nucmedbio.2004.11.006
PubMed ID:
15820759
Type:
Article
Language:
en
ISSN:
0969-8051
Appears in Collections:
All Christie Publications ; All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorDekker, Bronwen A-
dc.contributor.authorKeen, Heather G-
dc.contributor.authorLyons, Steve-
dc.contributor.authorDisley, Lynn-
dc.contributor.authorHastings, David L-
dc.contributor.authorReader, Andrew J-
dc.contributor.authorOttewell, Penny-
dc.contributor.authorWatson, Alastair-
dc.contributor.authorZweit, Jamal-
dc.date.accessioned2009-08-10T17:01:25Z-
dc.date.available2009-08-10T17:01:25Z-
dc.date.issued2005-04-
dc.identifier.citationMBP-annexin V radiolabeled directly with iodine-124 can be used to image apoptosis in vivo using PET. 2005, 32 (3):241-52 Nucl. Med. Biol.en
dc.identifier.issn0969-8051-
dc.identifier.pmid15820759-
dc.identifier.doi10.1016/j.nucmedbio.2004.11.006-
dc.identifier.urihttp://hdl.handle.net/10541/76835-
dc.description.abstractA noninvasive method of measuring programmed cell death in the tumors of cancer patients using positron-emission tomography (PET) would provide valuable information regarding their response to therapeutic intervention. Our strategy is to radiolabel annexin V, a protein that binds to phosphatidylserine moieties that are translocated to the external leaflet of plasma membranes during apoptosis. We developed a phosphatidylserine-ELISA capable of distinguishing wild type from point mutant annexin V that is known to have a lower phosphatidylserine binding affinity. A maltose-binding protein/annexin V chimera was synthesized and purified with high yield using amylose resin. We showed that it bound to phosphatidylserine in the ELISA as well as to that exposed on apoptotic Jurkat cells; therefore, it was used in the development of a method for radiolabeling annexin V using iodine radionuclides. MBP-annexin V retained its phosphatidylserine binding properties on direct iodination, but at high levels of oxidizing agents (iodogen and chloramine T), its specificity for phosphatidylserine was compromised. (124)I-MBP-annexin V was successfully used to image Fas-mediated hepatic cell death in BDF-1 mice using PET. In conclusion, we have shown that MBP-annexin V and the phosphatidylserine ELISA are useful tools for the development of methods for radiolabeling annexin V for PET imaging.en
dc.language.isoenen
dc.subject.meshAnimals-
dc.subject.meshAnnexin A5-
dc.subject.meshApoptosis-
dc.subject.meshCarrier Proteins-
dc.subject.meshHepatocytes-
dc.subject.meshHumans-
dc.subject.meshIodine Radioisotopes-
dc.subject.meshJurkat Cells-
dc.subject.meshLiver-
dc.subject.meshMale-
dc.subject.meshMetabolic Clearance Rate-
dc.subject.meshMice-
dc.subject.meshOrgan Specificity-
dc.subject.meshPositron-Emission Tomography-
dc.subject.meshRadiopharmaceuticals-
dc.subject.meshTissue Distribution-
dc.titleMBP-annexin V radiolabeled directly with iodine-124 can be used to image apoptosis in vivo using PET.en
dc.typeArticleen
dc.contributor.departmentCancer Research UK/UMIST, Department of Radiochemical Targeting and Imaging, Paterson Institute for Cancer Research, M20 4BX Manchester, UK.en
dc.identifier.journalNuclear Medicine and Biologyen

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