|
Title
|
|
|
|
In vitro and in vivo evaluation of -labeled tricarbonyl His-annexin A5 as an imaging agent for the detection of phosphatidylserine-expressing cells
|
|
|
Author
|
|
|
|
|
|
|
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. |
|
|
|
Language
|
|
|
|
English
|
|
|
Source (journal)
|
|
|
|
Nuclear geophysics. - Oxford, 1993, currens
|
|
|
Publication
|
|
|
|
Oxford
:
2010
|
|
|
ISSN
|
|
|
|
0969-8086
[print]
1878-6383
[online]
|
|
|
DOI
|
|
|
|
10.1016/J.NUCMEDBIO.2010.06.007
|
|
|
Volume/pages
|
|
|
|
37
:8
(2010)
, p. 965-975
|
|
|
ISI
|
|
|
|
000284456800014
|
|
|
Full text (Publisher's DOI)
|
|
|
|
|
|
|
Full text (publisher's version - intranet only)
|
|
|
|
|
|