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New neurotensin analogue radiolabeled by 99m-technetium as a potential agent for tumor identification.
- Source :
-
Chemical biology & drug design [Chem Biol Drug Des] 2018 Jan; Vol. 91 (1), pp. 304-313. Date of Electronic Publication: 2017 Sep 12. - Publication Year :
- 2018
-
Abstract
- It has been shown that more than 75% of ductal pancreatic adenocarcinomas overexpressed neurotensin (NT) receptors. Overexpression of NT receptors has been reported in various human tumor types. Hence, a non-invasive diagnosis and staging method could be very beneficial. In this work, we describe radiolabeling and evaluation of new neurotensin analogues to target neurotensin receptor-positive tumors such as pancreatic carcinoma. Radiolabeling was performed at 95°C for 10 min using <superscript>99m</superscript> Tc in the presence of tricine/EDDA exchange labeling. Radiochemical yield analysis involved ITLC and HPLC methods. A binding assay test was carried out in nine different concentrations of labeled neurotensin analogues in HT-29 cells. Radiopeptide-specific binding and internalization were studied in NT receptors expressing HT-29 cells. Biodistribution studies were performed in tumor-free BALB/c mice and HT-29 xenografted tumor-bearing nude mice. The peptide was efficiently labeled by <superscript>99m</superscript> Tc with high radiochemical yields (>98%). The radioconjugate was thoroughly stable in the solution and human serum even for 24 hr. The radiolabeled peptide showed high affinity (32.66 ± 4.01 nm) and specificity internalization (>%18 after 4 hr) to HT-29 cells. The radiopeptide efficiently showed tumor size and location in tumor-bearing nude mice. In biodistribution, a receptor-specific uptake of radiopeptide was observed in neurotensin receptor-positive organs such as intestine. Uptake in the tumor was 4.59 ± 0.23% ID/g after 2 hr. Owing to excellent stability, high affinity, rapid blood clearance, low accumulation in non-target organs, and high uptake in tumor, the <superscript>99m</superscript> Tc-HYNIC-peptide is a potential agent for targeting of NTR-overexpressing tumor cells in clinical surroundings. When successfully executed in the clinical surrounding, non-invasive imaging of NTR-positive tumors with <superscript>99m</superscript> Tc-labeled new neurotensin analogues could facilitate therapy procedure and monitoring.<br /> (© 2017 John Wiley & Sons A/S.)
- Subjects :
- Animals
Binding, Competitive
Female
HT29 Cells
Humans
Isotope Labeling
Mice
Mice, Inbred BALB C
Mice, Nude
Neurotensin pharmacokinetics
Protein Binding
Radiopharmaceuticals pharmacokinetics
Single Photon Emission Computed Tomography Computed Tomography
Technetium chemistry
Tissue Distribution
Transplantation, Heterologous
Neoplasms diagnosis
Neurotensin analogs & derivatives
Radiopharmaceuticals chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 1747-0285
- Volume :
- 91
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Chemical biology & drug design
- Publication Type :
- Academic Journal
- Accession number :
- 28816013
- Full Text :
- https://doi.org/10.1111/cbdd.13082