Novel targeted nuclear imaging agent for gastric cancer diagnosis: glucose-regulated protein 78 binding peptide-guided 111In-labeled polymeric micelles

Chun-Chia Cheng,1,2,* Chiung-Fang Huang,3,4,* Ai-Sheng Ho,5 Cheng-Liang Peng,6 Chun-Chao Chang,7,8 Fu-Der Mai,1,9 Ling-Yun Chen,10 Tsai-Yueh Luo,2 Jungshan Chang1,11,121Graduate Institute of Medical Sciences, Taipei Medical University, Taipei, 2Institute of Nuclear Energy Research, Atomic Energy Cou...

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Autores principales: Cheng CC, Huang CF, Ho AS, Peng CL, Chang CC, Mai FD, Chen LY, Luo TY, Chang J
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Publicado: Dove Medical Press 2013
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spelling oai:doaj.org-article:10d726b081524787881233320af9df482021-12-02T04:46:25ZNovel targeted nuclear imaging agent for gastric cancer diagnosis: glucose-regulated protein 78 binding peptide-guided 111In-labeled polymeric micelles1176-91141178-2013https://doaj.org/article/10d726b081524787881233320af9df482013-04-01T00:00:00Zhttp://www.dovepress.com/novel-targeted-nuclear-imaging-agent-for-gastric-cancer-diagnosis-gluc-a12712https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Chun-Chia Cheng,1,2,* Chiung-Fang Huang,3,4,* Ai-Sheng Ho,5 Cheng-Liang Peng,6 Chun-Chao Chang,7,8 Fu-Der Mai,1,9 Ling-Yun Chen,10 Tsai-Yueh Luo,2 Jungshan Chang1,11,121Graduate Institute of Medical Sciences, Taipei Medical University, Taipei, 2Institute of Nuclear Energy Research, Atomic Energy Council, Taoyuan, 3School of Dental Technology, Taipei Medical University, Taipei, 4Division of Family and Operative Dentistry, Department of Dentistry, Taipei Medical University Hospital, Taipei, 5Division of Gastroenterology, Cheng Hsin General Hospital, Taipei, 6Institute of Biomedical Engineering, National Taiwan University, Taipei, 7Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taipei Medical University Hospital, Taipei, 8Department of Internal Medicine, Taipei Medical University, Taipei, 9Department of Biochemistry, Taipei Medical University, Taipei, 10Institute of Biochemistry and Biotechnology, Chung Shan Medical University, Taichung, 11Neuroscience Research Center, Taipei Medical University Hospital, Taipei, 12Research Center for Biomedical Implants and Microsurgery Devices, Taipei Medical University, Taipei, Taiwan*These authors contributed equally to this workAbstract: Increased expression of cellular membrane bound glucose-regulated protein 78 (GRP78) is considered to be one of the biomarkers for gastric cancers. Therefore, peptides or molecules with specific recognition to GRP78 can act as a guiding probe to direct conjugated imaging agents to localized cancers. Based on this rationale, GRP78-guided polymeric micelles were designed and manufactured for nuclear imaging detection of tumors. Thiolated GRP78 binding peptide (GRP78BP) was first labeled with maleimide-terminated poly(ethylene glycol)&ndash;poly(&epsilon;-caprolactone) and then mixed with diethylenetriaminepentaacetic acid (DTPA)-linked poly(ethylene glycol)&ndash;poly(&epsilon;-caprolactone) to form DTPA/GRP78BP-conjugated micelles. The coupling efficiency of micelles with radioisotope indium-111 (111In) was measured and analyzed by instant thin layer chromatography. The coupling efficiency of DTPA-conjugated micelles and DTPA/GRP78BP-conjugated micelles with 111In was 85% and 93%, respectively. For characterization and trace imaging, the radioisotope 111In-targeting tumors were detected and imaged in a xenograft murine model using nano single photon emission computed tomography/computed tomography. The results revealed that the radioactive intensity measured in the animals administered with GRP78BP-guided 111In-labeled micelles was statistically higher than that in animals administered with 111In-labeled micelles, demonstrating that GRP78BP more than doubled the accumulation of micelles to the tumor tissue (P < 0.05). The results indicate that the gastric cancer biomarker GRP78 is a probing target in the application of nuclear imaging for tumor diagnosis. This novel GRP78BP-guided micelle agent may be applied in clinical practice to complement the histological diagnosis.Keywords: biomarker, glucose-regulated protein 78, nuclear imaging, gastric cancer, micellesCheng CCHuang CFHo ASPeng CLChang CCMai FDChen LYLuo TYChang JDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2013, Iss default, Pp 1385-1391 (2013)
institution DOAJ
collection DOAJ
language EN
topic Medicine (General)
R5-920
spellingShingle Medicine (General)
R5-920
Cheng CC
Huang CF
Ho AS
Peng CL
Chang CC
Mai FD
Chen LY
Luo TY
Chang J
Novel targeted nuclear imaging agent for gastric cancer diagnosis: glucose-regulated protein 78 binding peptide-guided 111In-labeled polymeric micelles
description Chun-Chia Cheng,1,2,* Chiung-Fang Huang,3,4,* Ai-Sheng Ho,5 Cheng-Liang Peng,6 Chun-Chao Chang,7,8 Fu-Der Mai,1,9 Ling-Yun Chen,10 Tsai-Yueh Luo,2 Jungshan Chang1,11,121Graduate Institute of Medical Sciences, Taipei Medical University, Taipei, 2Institute of Nuclear Energy Research, Atomic Energy Council, Taoyuan, 3School of Dental Technology, Taipei Medical University, Taipei, 4Division of Family and Operative Dentistry, Department of Dentistry, Taipei Medical University Hospital, Taipei, 5Division of Gastroenterology, Cheng Hsin General Hospital, Taipei, 6Institute of Biomedical Engineering, National Taiwan University, Taipei, 7Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taipei Medical University Hospital, Taipei, 8Department of Internal Medicine, Taipei Medical University, Taipei, 9Department of Biochemistry, Taipei Medical University, Taipei, 10Institute of Biochemistry and Biotechnology, Chung Shan Medical University, Taichung, 11Neuroscience Research Center, Taipei Medical University Hospital, Taipei, 12Research Center for Biomedical Implants and Microsurgery Devices, Taipei Medical University, Taipei, Taiwan*These authors contributed equally to this workAbstract: Increased expression of cellular membrane bound glucose-regulated protein 78 (GRP78) is considered to be one of the biomarkers for gastric cancers. Therefore, peptides or molecules with specific recognition to GRP78 can act as a guiding probe to direct conjugated imaging agents to localized cancers. Based on this rationale, GRP78-guided polymeric micelles were designed and manufactured for nuclear imaging detection of tumors. Thiolated GRP78 binding peptide (GRP78BP) was first labeled with maleimide-terminated poly(ethylene glycol)&ndash;poly(&epsilon;-caprolactone) and then mixed with diethylenetriaminepentaacetic acid (DTPA)-linked poly(ethylene glycol)&ndash;poly(&epsilon;-caprolactone) to form DTPA/GRP78BP-conjugated micelles. The coupling efficiency of micelles with radioisotope indium-111 (111In) was measured and analyzed by instant thin layer chromatography. The coupling efficiency of DTPA-conjugated micelles and DTPA/GRP78BP-conjugated micelles with 111In was 85% and 93%, respectively. For characterization and trace imaging, the radioisotope 111In-targeting tumors were detected and imaged in a xenograft murine model using nano single photon emission computed tomography/computed tomography. The results revealed that the radioactive intensity measured in the animals administered with GRP78BP-guided 111In-labeled micelles was statistically higher than that in animals administered with 111In-labeled micelles, demonstrating that GRP78BP more than doubled the accumulation of micelles to the tumor tissue (P < 0.05). The results indicate that the gastric cancer biomarker GRP78 is a probing target in the application of nuclear imaging for tumor diagnosis. This novel GRP78BP-guided micelle agent may be applied in clinical practice to complement the histological diagnosis.Keywords: biomarker, glucose-regulated protein 78, nuclear imaging, gastric cancer, micelles
format article
author Cheng CC
Huang CF
Ho AS
Peng CL
Chang CC
Mai FD
Chen LY
Luo TY
Chang J
author_facet Cheng CC
Huang CF
Ho AS
Peng CL
Chang CC
Mai FD
Chen LY
Luo TY
Chang J
author_sort Cheng CC
title Novel targeted nuclear imaging agent for gastric cancer diagnosis: glucose-regulated protein 78 binding peptide-guided 111In-labeled polymeric micelles
title_short Novel targeted nuclear imaging agent for gastric cancer diagnosis: glucose-regulated protein 78 binding peptide-guided 111In-labeled polymeric micelles
title_full Novel targeted nuclear imaging agent for gastric cancer diagnosis: glucose-regulated protein 78 binding peptide-guided 111In-labeled polymeric micelles
title_fullStr Novel targeted nuclear imaging agent for gastric cancer diagnosis: glucose-regulated protein 78 binding peptide-guided 111In-labeled polymeric micelles
title_full_unstemmed Novel targeted nuclear imaging agent for gastric cancer diagnosis: glucose-regulated protein 78 binding peptide-guided 111In-labeled polymeric micelles
title_sort novel targeted nuclear imaging agent for gastric cancer diagnosis: glucose-regulated protein 78 binding peptide-guided 111in-labeled polymeric micelles
publisher Dove Medical Press
publishDate 2013
url https://doaj.org/article/10d726b081524787881233320af9df48
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