NTR-1 Dotaz Zobrazit nápovědu
BACKGROUND: Neurotensin receptors are overexpressed in several cancer types including pancreatic ductal adenocarcinoma. Three NTR subtypes have been cloned: NTR-1, NTR-2 and NTR-3. The most expressed NTR-1 is not present in normal pancreatic tissue and has a low expression in chronic pancreatitis. OBJECTIVE: Objective of this study was to test in vitro affinity of the new 68Ga labelled neurotensin analogue DOTA-NT-20.3 (fragment 6-13, Ac-Lys(DOTA)-Pro-Arg(N-CH3)-Arg-Pro-Tyr-Tle-Leu) on the human pancreatic ductal adenocarcinoma cell line AsPC-1. METHOD: For the preparation of 68Ga-DOTA-NT-20.3, 68GaCl3 solution (eluted from 68Ge/68Ga generator) and 50 μg of precursor (Iason, Graz, Austria) water dissolved were used in an automatic synthesis module. The labeled compound was added to cell culture flask and incubated at 37°C. At various time points after tracer addition up to 80min, cells were recovered, rinsed and counted for radioactivity. Results were expressed as percent binding normalized to 200000 cells and affinity parameters were calculated. RESULTS: Labeling yield was ≥98 %. The molar ratio between labelled and total peptide was about 1/400. AsPC-1 cell line showed rapid uptake of the tracer including surface and internalized binding, tending to a plateau phase 80 min after tracer addition (11%/200.000 cells). The Kd (7.335 pmol) and Bmax (90.52 kBq) value indicated high tracer affinity for AsPC-1cell line especially if compared with the literature data regarding other malignancies (e.g. colonic cancer cell line). Binding sites were 1.09x106 sites per cell. CONCLUSION: New tracer 68Ga-DOTA-NT-20.3 can be a suitable candidate for the clinical use in patients with pancreatic ductal adenocarcinoma.
- MeSH
- adenokarcinom metabolismus patologie MeSH
- heterocyklické sloučeniny monocyklické chemie metabolismus MeSH
- lidé MeSH
- nádorové buněčné linie MeSH
- nádory slinivky břišní metabolismus patologie MeSH
- neurotensin agonisté chemie metabolismus MeSH
- peptidové fragmenty chemie metabolismus MeSH
- radioizotopy galia chemie metabolismus MeSH
- receptory neurotensinu metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: There is an urgent need to develop better materials to provide anatomical support to the pelvic floor without compromising its function. OBJECTIVE: Our aim was to assess outcomes after simulated vaginal prolapse repair in a sheep model using three different materials: (1) ultra-lightweight polypropylene (PP) non-degradable textile (Restorelle) mesh, (2) electrospun biodegradable ureidopyrimidinone-polycarbonate (UPy-PC), and (3) electrospun non-degradable polyurethane (PU) mesh in comparison with simulated native tissue repair (NTR). These implants may reduce implant-related complications and avoid vaginal function loss. DESIGN, SETTING, AND PARTICIPANTS: A controlled trial was performed involving 48 ewes that underwent NTR or mesh repair with PP, UPy-PC, or PU meshes (n=12/group). Explants were examined 60 and 180 d (six per group) post-implantation. INTERVENTION: Posterior rectovaginal dissection, NTR, or mesh repair. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Implant-related complications, vaginal contractility, compliance, and host response were assessed. Power calculation and analysis of variance testing were used to enable comparison between the four groups. RESULTS: There were no visible implant-related complications. None of the implants compromised vaginal wall contractility, and passive biomechanical properties were similar to those after NTR. Shrinkage over the surgery area was around 35% for NTR and all mesh-augmented repairs. All materials were integrated well with similar connective tissue composition, vascularization, and innervation. The inflammatory response was mild with electrospun implants, inducing both more macrophages yet with relatively more type 2 macrophages present at an early stage than the PP mesh. CONCLUSIONS: Three very different materials were all well tolerated in the sheep vagina. Biomechanical findings were similar for all mesh-augmented repair and NTR. Constructs induced slightly different mid-term inflammatory profiles. PATIENT SUMMARY: Product innovation is needed to reduce implant-related complications. We tested two novel implants, electrospun and an ultra-lightweight polypropylene textile mesh, in a physiologically relevant model for vaginal surgery. All gave encouraging outcomes.
- MeSH
- biokompatibilní materiály MeSH
- chirurgické síťky * MeSH
- gynekologické chirurgické výkony MeSH
- modely nemocí na zvířatech MeSH
- modely u zvířat MeSH
- ovce MeSH
- polypropyleny * MeSH
- prolaps dělohy chirurgie MeSH
- protézy - design MeSH
- pyrimidinony MeSH
- testování materiálů MeSH
- textilie MeSH
- výsledek terapie MeSH
- zvířata MeSH
- Check Tag
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- hodnotící studie MeSH
- práce podpořená grantem MeSH
Buňky duktálního adenokarcinomu pankreatu (PDAC) exprimují neurotenzinové receptory. Preklinické testy úspěšně ukázaly, že analogy neurotenzinu značené radionuklidy mají potenciál pro PET zobrazování duktálního adenokarcinomu pankreatu. První in vivo vyšetření pacientů s užitím 68Ga DOTA-NT-20.3 však na rozdíl od preklinických studií nezobrazily nádory PDAC ve všech případech s vysokým kontrastem vůči okolí. Pro praktické užití bude tedy nutno pokračovat v nadějném výzkumu na poli analogů neurotenzinu se snahou modifikovat postupy s cílem dále zvýšit afinitu peptidových radiofarmak k neurotenzinovým receptorům.
Cells of pancreatic ductal adenocarcinoma (PDAC) express neurotensin receptors. Preclinical trials have successfully shown that neurotensin analogues have the potential for PET imaging of PDAC. Based on the published data, NTR-1 is promising target for the development of radioactive analogues for both imaging and therapy in patients with primary and metastatic pancreatic ductal adenocarcinoma. However, the first in vivo studies using 68Ga DOTA-NT-20.3 in patients did not image PDAC tumours in all cases with very high contrast to surrounding tissue. Peptid research in the field of neurotensin analogues continues in an effort to further enhance the affinity of PET peptide radiopharmaceuticals for neurotensin receptors.
