Knottins As A Structural Basis For The Stabilization Of Radio Pharmaceuticals

The aim of the current reseach was to study synthesize a peptide tropic to the prostate-specific antigen and containing a cysteine knot. Materials and Methods : A comparative study of the efficiency of binding in vitro with prostate cancer cells of artificial peptides based on U5-scytotoxin-Sth1a toxin with an inserted peptide tropic to the prostate-specific membrane antigen and the radiopharmaceutical 177Lu-PSMA-617 is carried out. Three prostate cancer cell lines were used in the research. Results : Synthesized DOTA-Knot/C0-C1, DOTA-Knot/C1-C2 and DOTA-Knot/C2-C3 peptides containing the GTIQPYPFSWGY sequence inserted into U5-Sth1a knottin are more stable in blood plasma and saline and also show a similar degree of binding to LNCaP, PC3 cells compared with the 177Lu-PSMA-617 radiopharmaceutical. Conclusion : Modified peptides with a peptide tropic to the PSMA antigen inserted into the structure of U5-Sth1a demonstrate the greatest stability.

[1]  A. Rosato,et al.  Development of 177Lu-scFvD2B as a Potential Immunotheranostic Agent for Tumors Overexpressing the Prostate Specific Membrane Antigen , 2020, Scientific Reports.

[2]  Daniel Kwon,et al.  Insight into the Development of PET Radiopharmaceuticals for Oncology , 2020, Cancers.

[3]  J. Jamie,et al.  Methods to Enhance the Metabolic Stability of Peptide-Based PET Radiopharmaceuticals , 2020, Molecules.

[4]  B. Jowanaridhi,et al.  Radiolabeling efficiency and stability study on Lutetium-177 labeled bombesin peptide , 2019, Journal of Physics: Conference Series.

[5]  P. Geramifar,et al.  68Ga-radiolabeled bombesin-conjugated to trimethyl chitosan-coated superparamagnetic nanoparticles for molecular imaging: preparation, characterization and biological evaluation , 2019, International journal of nanomedicine.

[6]  R. Upadhyay Use of Animal Venom Peptides/Toxins in Cancer Therapeutics , 2018, Current Trends in Biomedical Engineering & Biosciences.

[7]  A. Jemal,et al.  Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries , 2018, CA: a cancer journal for clinicians.

[8]  W. Cai,et al.  Targeted α-therapy of prostate cancer using radiolabeled PSMA inhibitors: a game changer in nuclear medicine. , 2018, American journal of nuclear medicine and molecular imaging.

[9]  D. Lee,et al.  Development of a Ga-68 labeled PET tracer with short linker for prostate-specific membrane antigen (PSMA) targeting. , 2018, Bioorganic & medicinal chemistry.

[10]  S. Hosseinimehr,et al.  PASylation as a Powerful Technology for Improving the Pharmacokinetic Properties of Biopharmaceuticals. , 2017, Current Drug Delivery.

[11]  Mark S. Litwin,et al.  The Diagnosis and Treatment of Prostate Cancer: A Review , 2017, JAMA.

[12]  I. Castiglioni,et al.  Targeted radionuclide therapy: frontiers in theranostics. , 2017, Frontiers in bioscience.

[13]  A. Versari,et al.  Labelling of 90Y- and 177Lu-DOTA-Bioconjugates for Targeted Radionuclide Therapy: A Comparison among Manual, Semiautomated, and Fully Automated Synthesis , 2017, Contrast media & molecular imaging.

[14]  Matthew R. Cooperberg,et al.  Epidemiology of prostate cancer , 2017, World Journal of Urology.

[15]  Chuanqin Xia,et al.  68Ga/177Lu-labeled DOTA-TATE shows similar imaging and biodistribution in neuroendocrine tumor model , 2017, Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine.

[16]  Ming-Rong Zhang,et al.  Synthesis and evaluation of [64Cu]PSMA-617 targeted for prostate-specific membrane antigen in prostate cancer. , 2017, American journal of nuclear medicine and molecular imaging.

[17]  S. Mendiratta,et al.  HPLC for Peptides and Proteins: Principles, Methods and Applications , 2017 .

[18]  T. Pandolfini,et al.  Plant cystine-knot peptides: pharmacological perspectives. , 2017, British journal of clinical pharmacology.

[19]  Debadyuti Ghosh,et al.  Peptides as drug delivery vehicles across biological barriers , 2017, Journal of Pharmaceutical Investigation.

[20]  K. Rahbar,et al.  Radioligand therapy with 177Lu-PSMA-617 of metastatic prostate cancer has already been arrived in clinical use. , 2016, Nuclear medicine and biology.

[21]  J. Cochran,et al.  Integrin-Targeting Knottin Peptide-Drug Conjugates Are Potent Inhibitors of Tumor Cell Proliferation. , 2016, Angewandte Chemie.

[22]  I. Vetter,et al.  Characterization of Three Venom Peptides from the Spitting Spider Scytodes thoracica , 2016, PloS one.

[23]  R. Fimmers,et al.  Therapeutic response and side effects of repeated radioligand therapy with 177Lu-PSMA-DKFZ-617 of castrate-resistant metastatic prostate cancer , 2016, Oncotarget.

[24]  R. Baum,et al.  177Lu-Labeled Prostate-Specific Membrane Antigen Radioligand Therapy of Metastatic Castration-Resistant Prostate Cancer: Safety and Efficacy , 2016, The Journal of Nuclear Medicine.

[25]  Tadashi Kimura,et al.  High Proteolytic Resistance of Spider-Derived Inhibitor Cystine Knots , 2015, International journal of peptides.

[26]  Sergey V. Gudkov,et al.  Targeted Radionuclide Therapy of Human Tumors , 2015, International journal of molecular sciences.

[27]  V. Álvarez,et al.  Biodegradable Polymeric Microparticles as Drug Delivery Devices , 2015 .

[28]  J. Cochran,et al.  Cystine-knot peptides: emerging tools for cancer imaging and therapy , 2014, Expert review of proteomics.

[29]  G. Pasut Pegylation of Biological Molecules and Potential Benefits: Pharmacological Properties of Certolizumab Pegol , 2014, BioDrugs.

[30]  G. Binford,et al.  Spit and venom from scytodes spiders: a diverse and distinct cocktail. , 2014, Journal of proteome research.

[31]  Xiao-kun Zhao,et al.  Prostate Cancer: Current Treatment and Prevention Strategies , 2013, Iranian Red Crescent medical journal.

[32]  G. Fields,et al.  Introduction to Peptide Synthesis , 2012, Current protocols in protein science.

[33]  G. King,et al.  Spider-Venom Peptides as Bioinsecticides , 2012, Toxins.

[34]  Judith Webster,et al.  Protein identification by MALDI-TOF mass spectrometry. , 2012, Methods in molecular biology.

[35]  H. Kolmar Natural and engineered cystine knot miniproteins for diagnostic and therapeutic applications. , 2011, Current pharmaceutical design.

[36]  Patrick S Daugherty,et al.  Protease-resistant peptide ligands from a knottin scaffold library. , 2011, ACS chemical biology.

[37]  Xiao Xu,et al.  The xCELLigence system for real-time and label-free monitoring of cell viability. , 2011, Methods in molecular biology.

[38]  A. Zlotta,et al.  Role of surgery in high-risk localized prostate cancer. , 2010, Current oncology.

[39]  C. Catton,et al.  Radiation therapy in prostate cancer: a risk-adapted strategy. , 2010, Current oncology.

[40]  A. Massicano,et al.  Development of a new bombesin analog radiolabeled with lutetium-177: in vivo evaluation of the biological properties in Balb-C mice. , 2010, Cellular and Molecular Biology.

[41]  H. Rajabi,et al.  Radiolabeling of trastuzumab with 177Lu via DOTA, a new radiopharmaceutical for radioimmunotherapy of breast cancer. , 2009, Nuclear medicine and biology.

[42]  Y. Lu,et al.  Issues related to targeted delivery of proteins and peptides , 2006, The AAPS Journal.

[43]  Kit S Lam,et al.  From combinatorial chemistry to cancer-targeting peptides. , 2007, Molecular pharmaceutics.

[44]  S. Baboota,et al.  Recent advances in protein and peptide drug delivery systems. , 2007, Current drug delivery.

[45]  H. Lepor,et al.  Androgen deprivation therapy in the treatment of advanced prostate cancer. , 2007, Reviews in urology.

[46]  A. Rajasekaran,et al.  Is prostate-specific membrane antigen a multifunctional protein? , 2005, American journal of physiology. Cell physiology.

[47]  Stephan Gabos,et al.  Dynamic monitoring of cytotoxicity on microelectronic sensors. , 2005, Chemical research in toxicology.

[48]  I. Tannock,et al.  Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. , 2004, The New England journal of medicine.

[49]  Michelle L Colgrave,et al.  Thermal, chemical, and enzymatic stability of the cyclotide kalata B1: the importance of the cyclic cystine knot. , 2004, Biochemistry.

[50]  J. Reubi Peptide receptors as molecular targets for cancer diagnosis and therapy. , 2003, Endocrine reviews.

[51]  Vladimir P Torchilin,et al.  Peptide and protein drug delivery to and into tumors: challenges and solutions. , 2003, Drug discovery today.

[52]  R. Norton,et al.  The cystine knot structure of ion channel toxins and related polypeptides. , 1998, Toxicon : official journal of the International Society on Toxinology.

[53]  N. Bander,et al.  Constitutive and antibody-induced internalization of prostate-specific membrane antigen. , 1998, Cancer research.

[54]  P. Schellhammer,et al.  Expression of prostate-specific membrane antigen in normal, benign, and malignant prostate tissues. , 1995, Urologic oncology.

[55]  S. Kariya Radiation Therapy for Prostate Cancer , 2013 .

[56]  J. Higginson,et al.  International Agency for Research on Cancer. , 1968, WHO chronicle.