PMID- 25344147
OWN - NLM
STAT- MEDLINE
DCOM- 20160308
LR  - 20240325
IS  - 1860-2002 (Electronic)
IS  - 1536-1632 (Print)
IS  - 1536-1632 (Linking)
VI  - 17
IP  - 3
DP  - 2015 Jun
TI  - Imaging caspase-3 activation as a marker of apoptosis-targeted treatment response 
      in cancer.
PG  - 384-93
LID - 10.1007/s11307-014-0802-8 [doi]
AB  - PURPOSE: We tested whether positron emission tomography (PET) with the 
      caspase-3-targeted isatin analog [(18)F]WC-4-116 could image caspase-3 activation 
      in response to an apoptosis-inducing anticancer therapy. PROCEDURES: 
      [(18)F]WC-4-116 uptake was determined in etoposide-treated EL4 cells. 
      Biodistribution studies with [(18)F]WC-4-116 and [(18)F]ICMT-18, a 
      non-caspase-3-targeted tracer, as well as [(18)F]WC-4-116 microPET imaging 
      assessed responses in Colo205 tumor-bearing mice treated with death receptor 5 
      (DR5)-targeted agonist antibodies. Immunohistochemical staining and enzyme assays 
      confirmed caspase-3 activation. Two-way analysis of variance or Student's t test 
      assessed for treatment-related changes in tracer uptake. RESULTS: [(18)F]WC-4-116 
      increased 8 +/- 2 fold in etoposide-treated cells. The [(18)F]WC-4-116 % ID/g also 
      increased significantly in tumors with high caspase-3 enzyme activity (p < 0.05). 
      [(18)F]ICMT-18 tumor uptake did not differ in tumors with high or low caspase-3 
      enzyme activity. CONCLUSIONS: [(18)F]WC-4-116 uptake in vivo reflects increased 
      caspase-3 activation and may be useful for detecting caspase-3-mediated apoptosis 
      treatment responses in cancer.
FAU - Chen, Delphine L
AU  - Chen DL
AD  - Division of Radiological Sciences and Nuclear Medicine, Mallinckrodt Institute of 
      Radiology, Washington University School of Medicine, Campus Box 8225, 510 S. 
      Kingshighway Blvd., St. Louis, MO, 63110, USA, chend@mir.wustl.edu.
FAU - Engle, Jacquelyn T
AU  - Engle JT
FAU - Griffin, Elizabeth A
AU  - Griffin EA
FAU - Miller, J Philip
AU  - Miller JP
FAU - Chu, Wenhua
AU  - Chu W
FAU - Zhou, Dong
AU  - Zhou D
FAU - Mach, Robert H
AU  - Mach RH
LA  - eng
GR  - K08 EB006702/EB/NIBIB NIH HHS/United States
GR  - P30 CA091842/CA/NCI NIH HHS/United States
GR  - R21 CA121952/CA/NCI NIH HHS/United States
GR  - R33 CA121952/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Mol Imaging Biol
JT  - Molecular imaging and biology
JID - 101125610
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Fluorine Radioisotopes)
RN  - 0 (Radiopharmaceuticals)
RN  - 0 (Receptors, TNF-Related Apoptosis-Inducing Ligand)
RN  - 0 (Sulfonamides)
RN  - 0 (WC-4-116)
RN  - 82X95S7M06 (Isatin)
RN  - EC 3.4.22.- (Caspase 3)
RN  - EC 3.4.22.- (Caspase 7)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents/*chemistry
MH  - *Apoptosis
MH  - Caspase 3/*metabolism
MH  - Caspase 7/metabolism
MH  - Cell Line, Tumor
MH  - Female
MH  - Fluorine Radioisotopes/chemistry
MH  - HeLa Cells
MH  - Humans
MH  - Immunohistochemistry
MH  - Inhibitory Concentration 50
MH  - Isatin/analogs & derivatives/chemistry
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Nude
MH  - Neoplasms/diagnostic imaging/*drug therapy/*enzymology
MH  - Positron-Emission Tomography
MH  - Radiopharmaceuticals
MH  - Receptors, TNF-Related Apoptosis-Inducing Ligand/metabolism
MH  - Sulfonamides/chemistry
MH  - Tissue Distribution
PMC - PMC4874215
MID - NIHMS782574
COIS- CONFLICT OF INTEREST The authors declare that they have no conflicts of interest.
EDAT- 2014/10/26 06:00
MHDA- 2016/03/10 06:00
PMCR- 2016/06/01
CRDT- 2014/10/26 06:00
PHST- 2014/10/26 06:00 [entrez]
PHST- 2014/10/26 06:00 [pubmed]
PHST- 2016/03/10 06:00 [medline]
PHST- 2016/06/01 00:00 [pmc-release]
AID - 10.1007/s11307-014-0802-8 [doi]
PST - ppublish
SO  - Mol Imaging Biol. 2015 Jun;17(3):384-93. doi: 10.1007/s11307-014-0802-8.