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Identifier

000449430

Title

Μελέτη συνδυαστικής χρήσης ραδιοπεπτιδίων μπομπεσίνης και νευροτενσίνης στην στόχευση του καρκίνου του προστάτη

Alternative Title

A study of the combined use of bombesin and neurotensin radiopeptides in prostate cancer targeting

Author

Μπιμπίκα, Μαρία

Thesis advisor

Μαϊνα Νοκ, Θεοδοσία

Reviewer

Κουκουράκη, Σοφία
Πίντζας, Αλέξανδρος

Abstract

Peptide radiopharmaceuticals target G protein-coupled receptors (GPCRs), which are overexpressed in specific types of cancer. The low metabolic stability of radiopeptides compromises their safe delivery to tumor sites. Proteolytic enzymes, proteases or peptidases (e.g. NEP) degrade them after entry in the circulation. Structure modifications in the peptide chain and/or the application of suitable protease inhibitors may improve metabolic stability. Some tumors overexpress more than one receptortarget. For instance, prostate cancer overexpresses gastrin-releasing peptide receptors (GRPRs) and neurotensin subtype 1 receptors (NTS1Rs). The aim of the present study was to evaluate potential advantages of combined GRPRs and NTS1Rs targeting of prostate cancer using a mixture of bombesin and neurotensin analogs labeled with technetium-99m. The impact of NEP inhibition following administration of Entresto® on the metabolic stability and tumor uptake of the radiopeptides was also assessed. Internalization and cellular uptake of either [99mTc]Tc-DT10 or of the [99mTc]Tc-DB7 and [99mTc]Tc-DT10 mixture were assessed in prostate cancer PC-3 cells. The metabolic stability of [99mTc]Tc-DT10 was assessed by HPLC of blood samples collected 5 min post-injection in healthy mice, treated or not with Entresto®. Biodistribution experiments of either [99mTc]Tc-DT10 or of the [99mTc]Tc-DB7 and [99mTc]Tc-DT10 mixture and SPECT/CT were conducted 4 h post-injection in immunosuppressed mice bearing PC- 3 xenografts; the impact of Entresto® was also investigated The uptake of the [99mTc]Tc-DB7 and [99mTc]Tc-DT10 mixture in PC-3 cells increased compared with [99mTc]Τc-DT10. The metabolic stability of [99mTc]Τc-DT10 was found significantly enhanced in the mice treated with Entresto®. The tumor uptake of the [99mTc]Tc-DB7 and [99mTc]Tc-DT10 mixture increased compared to that of either [99mTc]Tc-DB7 or [99mTc]Tc-DT10. A further increase in tumor values was induced by Entresto®. In conclusion, combined targeting of GRPRs και NTS1Rs prostate cancer with coadministration of [99mTc]Tc-DB7 and [99mTc]Tc-DT10 led to improved tumor uptake, without negatively affecting pharmacokinetics.

Language

Greek, English

Subject

Entresto

Gastrin-releasing peptide receptor (GRPR))

Neprilys;inh (NEP)

Neurotensin 1 subtype receptor (NTS1R)

Technetium-99m

Μπομπεσίνη (ΒΒΝ)

Νευροτενσίνη (ΝΤ)

Τεχνήτιο-99m

Υποδοχέας γαστρινοεκλυτικού πεπτιδίου (FRPR)