Preliminary in vivo evaluation of a novel 99mTc-labeled HYNIC-cys-annexin A5 as an apoptosis imaging agent.
A novel cys-annexin A5 with a single cysteine-residue at its concave side has been developed by site-directed mutagenesis to allow conjugation through thiol-chemistry without affecting its apoptotic cell binding properties and was derivatized with HYNIC in a 1:1 stoichiometry. Similar to that of the 1st generation 99mTc-HYNIC-annexin A5, the novel 99mTc-HYNIC-cys-annexin A5 derivative shows in normal mice mainly renal and, to a lesser extent, hepatobiliary excretion. In murine models of hepatic apoptosis there was 257% increase in hepatic uptake of 99mTc-HYNIC-cys-annexin A5 as compared to normal mice. Using the novel tracer agent, acute reperfused myocardial infarction in rabbits was unequivocally delineated at 7h post-injection by muSPECT. The results indicate that the novel 99mTc-HYNIC-cys-annexin A5 shows similar apoptosis avidity as the 1st generation 99mTc-HYNIC-annexin A5.
Laboratory for Radiopharmacy, Faculty of Pharmaceutical Sciences, K.U. Leuven, O&N 2, Box 821, Herestraat 49, BE-3000 Leuven, Belgium.
Humphrey
H
Fonge
Marijke
M
de Saint Hubert
Kathleen
K
Vunckx
Dirk
D
Rattat
Johan
J
Nuyts
Guy
G
Bormans
Yicheng
Y
Ni
Chris
C
Reutelingsperger
Alfons
A
Verbruggen
D000818:Animals; D017304:Annexin A5 / Q000737:chemistry* / Q000494:pharmacology; D017209:Apoptosis; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003545:Cysteine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D015195:Drug Design; D008099:Liver / Q000378:metabolism; D051379:Mice; D008956:Models, Chemical; D009203:Myocardial Infarction / Q000378:metabolism; D015609:Organotechnetium Compounds / Q000494:pharmacology*; D011817:Rabbits; D013438:Sulfhydryl Compounds / Q000737:chemistry; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods
D017304:Annexin A5; D015609:Organotechnetium Compounds; D013438:Sulfhydryl Compounds; C515026:technetium 99m cysteine; C117287:technetium Tc 99m HYNIC annexin V; D003545:Cysteine