دورية أكاديمية
Tumor-Specific Binding of Radiolabeled PEGylated GIRLRG Peptide: A Novel Agent for Targeting Cancers.
| العنوان: | Tumor-Specific Binding of Radiolabeled PEGylated GIRLRG Peptide: A Novel Agent for Targeting Cancers. |
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| المؤلفون: | Kapoor V; Department of Radiation Oncology, Washington University in St. Louis, St. Louis, Missouri., Dadey DY; Department of Radiation Oncology, Washington University in St. Louis, St. Louis, Missouri.; Medical Scientist Training Program, Washington University in St. Louis, St. Louis, Missouri., Nguyen K; Department of Radiation Oncology, Washington University in St. Louis, St. Louis, Missouri.; Mallinckrodt Institute of Radiology, Washington University in St. Louis, St. Louis, Missouri., Wildman SA; Carbone Cancer Center, University of Wisconsin, Madison, Wisconsin., Hoye K; Medical Guidance Systems, St. Louis, Missouri; and., Khudanyan A; Department of Radiation Oncology, Washington University in St. Louis, St. Louis, Missouri., Bandara N; Department of Radiation Oncology, Washington University in St. Louis, St. Louis, Missouri.; Mallinckrodt Institute of Radiology, Washington University in St. Louis, St. Louis, Missouri., Rogers BE; Department of Radiation Oncology, Washington University in St. Louis, St. Louis, Missouri.; Mallinckrodt Institute of Radiology, Washington University in St. Louis, St. Louis, Missouri., Thotala D; Department of Radiation Oncology, Washington University in St. Louis, St. Louis, Missouri dhallahan@radonc.wustl.edu dthotala@radonc.wustl.edu.; Siteman Cancer Center, School of Medicine, Washington University in St. Louis, St. Louis, Missouri., Hallahan DE; Department of Radiation Oncology, Washington University in St. Louis, St. Louis, Missouri dhallahan@radonc.wustl.edu dthotala@radonc.wustl.edu.; Mallinckrodt Institute of Radiology, Washington University in St. Louis, St. Louis, Missouri.; Siteman Cancer Center, School of Medicine, Washington University in St. Louis, St. Louis, Missouri. |
| المصدر: | Journal of nuclear medicine : official publication, Society of Nuclear Medicine [J Nucl Med] 2016 Dec; Vol. 57 (12), pp. 1991-1997. Date of Electronic Publication: 2016 Jul 21. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Society of Nuclear Medicine Country of Publication: United States NLM ID: 0217410 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1535-5667 (Electronic) Linking ISSN: 01615505 NLM ISO Abbreviation: J Nucl Med Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Reston, VA : Society of Nuclear Medicine Original Publication: [Chicago, Ill.] : S.N. Turiel & Assoc. |
| مواضيع طبية MeSH: | Adenocarcinoma/*metabolism , Oligopeptides/*chemistry , Oligopeptides/*metabolism , Polyethylene Glycols/*chemistry, A549 Cells ; Adenocarcinoma/diagnostic imaging ; Adenocarcinoma/pathology ; Adenosine Triphosphatases/metabolism ; Amino Acid Sequence ; Animals ; Endoplasmic Reticulum Chaperone BiP ; Female ; Heat-Shock Proteins/chemistry ; Heat-Shock Proteins/metabolism ; Humans ; Mice ; Models, Molecular ; Protein Binding ; Protein Domains ; Substrate Specificity |
| مستخلص: | Cancer-specific targeting sparing normal tissues would significantly enhance cancer therapy outcomes and reduce cancer-related mortality. One approach is to target receptors or molecules that are specifically expressed on cancer cells. Peptides as cancer-specific targeting agents offer advantages such as ease of synthesis, low antigenicity, and enhanced diffusion into tissues. Glucose-regulated protein 78 (GRP78) is an endoplasmic reticulum stress chaperone that regulates the unfolded protein response and is overexpressed in various cancers. In this study, we evaluated GIRLRG peptide that specifically targets GRP78 for cancer-specific binding (in vitro) and noninvasive tumor imaging (in vivo). Methods: GIRLRG peptide was modeled into the GRP78 ATPase domain using computational modeling. Surface plasmon resonance studies were performed to determine the affinity of GIRLRG peptide to GRP78 protein. GIRLRG was conjugated with PEG to prolong its circulation in mice. Tumor binding efficacy of PEG-GIRLRG peptide was evaluated in nude mice bearing heterotopic cervical (HT3), esophageal (OE33), pancreatic (BXPC3), lung (A549), and glioma (D54) tumors. Nano-SPECT/CT imaging of the mice was performed 48 and 72 h after injection with 111 In-labeled PEG-GIRLRG or PEG-control peptide. Post-SPECT biodistribution studies were performed 96 h after injection of the radiolabeled peptides. Results: Using molecular modeling and surface plasmon resonance, we identified that GIRLRG was binding with an affinity constant of 2.16 × 10 -3 M in the ATPase domain of GRP78. GIRLRG peptide specifically bound to cervical, lung, esophageal, and glioma cells. SPECT imaging revealed that 111 In-PEG-GIRLRG specifically bound to cervical, esophageal, pancreatic, lung, and brain tumors. Post-SPECT biodistribution data also validated the SPECT imaging results. Conclusion: GIRLRG peptide specifically binds to the ATPase domain of GRP78. Radiolabeled PEG-GIRLRG could be used to target various cancers. Further studies would be required to translate PEG-GIRLRG peptide into the clinic. (© 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.) |
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| معلومات مُعتمدة: | P30 CA091842 United States CA NCI NIH HHS; R01 CA112385 United States CA NCI NIH HHS; R01 CA125757 United States CA NCI NIH HHS; R01 CA140220 United States CA NCI NIH HHS |
| فهرسة مساهمة: | Keywords: GIRLRG peptide; GRP78; SPECT; molecular imaging |
| المشرفين على المادة: | 0 (Endoplasmic Reticulum Chaperone BiP) 0 (HSPA5 protein, human) 0 (Heat-Shock Proteins) 0 (Hspa5 protein, mouse) 0 (Oligopeptides) 3WJQ0SDW1A (Polyethylene Glycols) EC 3.6.1.- (Adenosine Triphosphatases) |
| تواريخ الأحداث: | Date Created: 20160723 Date Completed: 20170515 Latest Revision: 20211204 |
| رمز التحديث: | 20221213 |
| مُعرف محوري في PubMed: | PMC5126697 |
| DOI: | 10.2967/jnumed.115.165118 |
| PMID: | 27445290 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1535-5667 |
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| DOI: | 10.2967/jnumed.115.165118 |