|
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)) |
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Neprilys;inh (NEP) |
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Neurotensin 1 subtype receptor (NTS1R) |
|
Technetium-99m |
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Μπομπεσίνη (ΒΒΝ) |
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Νευροτενσίνη (ΝΤ) |
|
Τεχνήτιο-99m |
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Υποδοχέας γαστρινοεκλυτικού πεπτιδίου (FRPR) |
|
Υποδοχέας υπότυπου 1 νευροτενσίνης (NTS1R) |
Issue date |
2022-07-29 |
Collection
|
School/Department--School of Medicine--Department of Medicine--Post-graduate theses
|
|
Type of Work--Post-graduate theses
|
Views |
284 |