PET imaging of apoptosis with 64Cu-labeled streptavidin following pretargeting of phosphatidylserine with biotinylated annexin-V View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2006-09-22

AUTHORS

Nicole Cauchon, Réjean Langlois, Jacques A. Rousseau, Guillaume Tessier, Jules Cadorette, Roger Lecomte, Darel J. Hunting, Roberto A. Pavan, Stefan K. Zeisler, Johan E. van Lier

ABSTRACT

PurposeIn vivo detection of apoptosis is a diagnostic tool with potential clinical applications in cardiology and oncology. Radiolabeled annexin-V (anxV) is an ideal probe for in vivo apoptosis detection owing to its strong affinity for phosphatidylserine (PS), the molecular flag on the surface of apoptotic cells. Most clinical studies performed to visualize apoptosis have used 99mTc-anxV; however, its poor distribution profile often compromises image quality. In this study, tumor apoptosis after therapy was visualized by positron emission tomography (PET) using 64Cu-labeled streptavidin (SAv), following pre-targeting of apoptotic cells with biotinylated anxV. MethodsApoptosis was induced in tumor-bearing mice by photodynamic therapy (PDT) using phthalocyanine dyes as photosensitizers, and red light. After PDT, mice were injected i.v. with biotinylated anxV, followed 2 h later by an avidin chase, and after another 2 h with 64Cu-DOTA-biotin-SAv. PET images were subsequently recorded up to 13 h after PDT.ResultsPET images delineated apoptosis in treated tumors as early as 30 min after 64Cu-DOTA-biotin-SAv administration, with tumor-to-background ratios reaching a maximum at 3 h post-injection, i.e., 7 h post-PDT. Omitting the administration of biotinylated anxV or the avidin chase failed to provide a clear PET image, confirming that all three steps are essential for adequate visualization of apoptosis. Furthermore, differences in action mechanisms between photosensitizers that target tumor cells directly or via initial vascular stasis were clearly recognized through differences in tracer uptake patterns detecting early or delayed apoptosis.ConclusionThis study demonstrates the efficacy of a three-step 64Cu pretargeting procedure for PET imaging of apoptosis. Our data also confirm the usefulness of small animal PET to evaluate cancer treatment protocols. More... »

PAGES

247-258

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s00259-006-0199-y

DOI

http://dx.doi.org/10.1007/s00259-006-0199-y

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1015397815

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/17021816


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34 schema:description PurposeIn vivo detection of apoptosis is a diagnostic tool with potential clinical applications in cardiology and oncology. Radiolabeled annexin-V (anxV) is an ideal probe for in vivo apoptosis detection owing to its strong affinity for phosphatidylserine (PS), the molecular flag on the surface of apoptotic cells. Most clinical studies performed to visualize apoptosis have used 99mTc-anxV; however, its poor distribution profile often compromises image quality. In this study, tumor apoptosis after therapy was visualized by positron emission tomography (PET) using 64Cu-labeled streptavidin (SAv), following pre-targeting of apoptotic cells with biotinylated anxV. MethodsApoptosis was induced in tumor-bearing mice by photodynamic therapy (PDT) using phthalocyanine dyes as photosensitizers, and red light. After PDT, mice were injected i.v. with biotinylated anxV, followed 2 h later by an avidin chase, and after another 2 h with 64Cu-DOTA-biotin-SAv. PET images were subsequently recorded up to 13 h after PDT.ResultsPET images delineated apoptosis in treated tumors as early as 30 min after 64Cu-DOTA-biotin-SAv administration, with tumor-to-background ratios reaching a maximum at 3 h post-injection, i.e., 7 h post-PDT. Omitting the administration of biotinylated anxV or the avidin chase failed to provide a clear PET image, confirming that all three steps are essential for adequate visualization of apoptosis. Furthermore, differences in action mechanisms between photosensitizers that target tumor cells directly or via initial vascular stasis were clearly recognized through differences in tracer uptake patterns detecting early or delayed apoptosis.ConclusionThis study demonstrates the efficacy of a three-step 64Cu pretargeting procedure for PET imaging of apoptosis. Our data also confirm the usefulness of small animal PET to evaluate cancer treatment protocols.
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42 ConclusionThis study
43 MethodsApoptosis
44 PET images
45 PET imaging
46 ResultsPET images
47 SAv administration
48 action mechanism
49 adequate visualization
50 administration
51 affinity
52 animal positron emission tomography
53 anxV.
54 apoptosis
55 apoptosis detection
56 apoptotic cells
57 applications
58 avidin chase
59 background ratio
60 biotinylated anxV
61 cancer treatment protocols
62 cardiology
63 cells
64 chase
65 clear PET image
66 clinical applications
67 clinical studies
68 data
69 detection
70 detection of apoptosis
71 diagnostic tool
72 differences
73 distribution profiles
74 dye
75 efficacy
76 emission tomography
77 flags
78 ideal probe
79 image quality
80 images
81 imaging
82 initial vascular stasis
83 light
84 maximum
85 mechanism
86 mice
87 min
88 molecular flag
89 most clinical studies
90 oncology
91 patterns
92 phosphatidylserine
93 photodynamic therapy
94 photosensitizer
95 phthalocyanine dyes
96 poor distribution profile
97 positron emission tomography
98 potential clinical applications
99 pretargeting
100 pretargeting of phosphatidylserine
101 probe
102 procedure
103 profile
104 protocol
105 purposeIn
106 quality
107 ratio
108 red light
109 small animal positron emission tomography
110 stasis
111 step
112 streptavidin
113 strong affinity
114 study
115 surface
116 therapy
117 three-step 64Cu
118 tomography
119 tool
120 tracer uptake patterns
121 treatment protocol
122 tumor apoptosis
123 tumor cells
124 tumor-bearing mice
125 tumors
126 uptake patterns
127 usefulness
128 vascular stasis
129 visualization
130 vivo apoptosis detection
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