In vivo imaging of tumor apoptosis using histone H1-targeting peptide.
In vivo imaging of apoptosis could allow monitoring of tumor response to cancer treatments such as chemotherapy. Using phage display, we identified the CQRPPR peptide, named ApoPep-1(Apoptosis-targeting Peptide-1), that was able to home to apoptotic and necrotic cells in tumor tissue. ApoPep-1 also bound to apoptotic and necrotic cells in culture, while only little binding to live cells was observed. Its binding to apoptotic cells was not dependent on calcium ion and not competed by annexin V. The receptor for ApoPep-1 was identified to be histone H1 that was exposed on the surface of apoptotic cells. In necrotic cells, ApoPep-1 entered the cells and bound to histone H1 in the nucleus. The imaging signals produced during monitoring of tumor apoptosis in response to chemotherapy was enhanced by the homing of a fluorescent dye- or radioisotope-labeled ApoPep-1 to tumor treated with anti-cancer drugs, whereas its uptake of the liver and lung was minimal. These results suggest that ApoPep-1 holds great promise as a probe for in vivo imaging of apoptosis, while histone H1 is a unique molecular signature for this purpose.
Wang
Kai
K
Department of Biochemistry and Cell Biology, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.
Purushotham
Sangeetha
S
Lee
Ji-Young
JY
Na
Moon-Hee
MH
Park
Hyekyung
H
Oh
Sun-Jeong
SJ
Park
Rang-Woon
RW
Park
Jae Yong
JY
Lee
Eungbae
E
Cho
Byung Chae
BC
Song
Mi-Na
MN
Baek
Moon-Chang
MC
Kwak
Wonjung
W
Yoo
Jeongsoo
J
Hoffman
Allan S
AS
Oh
Yu-Kyoung
YK
Kim
In-San
IS
Lee
Byung-Heon
BH
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D045744:Cell Line, Tumor; D005260:Female; D006657:Histones / Q000378:metabolism*; D006801:Humans; D008264:Macrophages / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D009336:Necrosis; D009369:Neoplasms / Q000175:diagnosis* / Q000473:pathology; D009842:Oligopeptides / Q000737:chemistry / Q000378:metabolism; D019151:Peptide Library; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D049268:Positron-Emission Tomography; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley
D006657:Histones; D009842:Oligopeptides; D019151:Peptide Library; D010455:Peptides; C578342:cysteinyl-glutaminyl-arginyl-prolyl-prolyl-arginine