Title
In vitro and in vivo evaluation of <tex>$[^{99m}Tc]$</tex>-labeled tricarbonyl His-annexin A5 as an imaging agent for the detection of phosphatidylserine-expressing cells
Author
Faculty/Department
Faculty of Medicine and Health Sciences
Publication type
article
Publication
Subject
Biology
Pharmacology. Therapy
Source (journal)
Nuclear medicine and biology
Volume/pages
37(2010) :8 , p. 965-975
ISSN
0969-8086
Carrier
E
Target language
English (eng)
Full text (Publishers DOI)
Affiliation
University of Antwerp
Abstract
Introduction Apoptosis is one of the mechanisms behind successful chemotherapy and radiation treatment. Radiolabeled annexin A5 has been demonstrated to be a successful tool in the detection of apoptosis following chemotherapy in vivo. Methods His-tagged annexin A5 was labeled with [99mTc]-tricarbonyl and evaluated as apoptosis imaging radiotracer in vitro and in vivo. The binding of the radiotracer was evaluated in Colo205 cells stimulated with 5-FU (1 mM) for 4 and 24 h, and confirmed by flow cytometry. Biodistribution and dosimetric studies were performed in healthy nude mice (n=5) via planar scintigraphy. [99mTc]-(CO)3 His-annexin A5 was also evaluated for in vivo imaging of spontaneous apoptosis in Colo205-bearing mice (n=12). Results The labeling procedure yielded a compound with 95-99% radiochemical purity and good in vitro stability. In vitro binding experiments indicated that the radiotracer retained its PS-binding activity. [99mTc]-(CO)3 His-annexin A5 rapidly cleared from the blood and predominantly accumulated in the kidneys. Absorbed dose (per organ) was found to be 116±64 μGy/MBq for the kidneys and 10.38±0.50 μGy/MBq for the liver. The effective dose was 7.00±0.28 μSv/MBq. Spontaneous apoptosis in Colo205-bearing mice was visualised by [99mTc]-(CO)3 His-annexin A5 SPECT and correlated well with caspase-3 immunostaining (R=0.867, P<.01). Conclusion [99mTc]-(CO)3 His-annexin A5 may be a useful novel radioligand for the in vivo detection of cell death associated with PS expression. A simple, noninvasive way of detecting apoptosis in vivo could have many applications including a better understanding of the extent and timing of apoptosis in response to cancer therapies and assessment of early tumor response.
E-info
https://repository.uantwerpen.be/docman/iruaauth/ddda3a/f1a301f67fb.pdf
Handle