scholarly journals The Crystal Structure Elucidation of a Tetrapeptide Analog of Somatostatin DOTA-Phe-D-Trp-Lys-Thr-OMe

Crystals ◽  
2021 ◽  
Vol 12 (1) ◽  
pp. 12
Author(s):  
Sabina Diusenova ◽  
Sergey Arkhipov ◽  
Dmitry Avdeev ◽  
Pavel Dorovatovskii ◽  
Derenik Khachatryan ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Active Site ◽  
Targeted Drug Delivery ◽  
Radionuclide Therapy ◽  
Structure Elucidation ◽  
Peptide Receptor Radionuclide Therapy ◽  
Peptide Receptor ◽  
Targeted Drug ◽  
First Time ◽  
Targeted Drug Delivery System

Herewith, we report for the first time the crystal structure of tetrapeptide FwKT (Phe-D-Trp-Lys-Thr), which is considered to represent an epitope for biomedically relevant hormone somatostatin. The target molecule was successfully crystalized, solved and refined as a conjugate of the tetrapeptide moiety bearing a protective group DOTA at the N-terminus and methylated at the O-terminus. The combination of a hormone active site and a powerful chelator make the substance a highly prospective targeted drug delivery system, especially for peptide receptor radionuclide therapy (PRRT) applications.

Peptide Receptor Radionuclide Therapy for Pancreatic Neuroendocrine Tumours

2019 ◽  
Vol 12 (2) ◽  
pp. 126-134 ◽  
Author(s):  
Shahad Alsadik ◽  
Siraj Yusuf ◽  
Adil AL-Nahhas
Keyword(s):  
Side Effects ◽  
Effective Treatment ◽  
Radionuclide Therapy ◽  
Neuroendocrine Tumours ◽  
Peptide Receptor Radionuclide Therapy ◽  
Progression Free Survival ◽  
Treatment Modalities ◽  
Effective Treatment Option ◽  
Peptide Receptor ◽  
Pancreatic Neuroendocrine Tumours

Background: The incidence of pancreatic Neuroendocrine Tumours (pNETs) has increased considerably in the last few decades. The characteristic features of this tumour and the development of new investigative and therapeutic methods had a great impact on its management. Objective: The aim of this review is to investigate the outcome of Peptide Receptor Radionuclide Therapy (PRRT) in the treatment of pancreatic neuroendocrine tumours. Methods: A comprehensive literature search strategy was used based on two databases (SCOPUS, and PubMed). We considered all studies published in English, evaluating the use of PRRT (177Luteciuim- DOTA-conjugated peptides and 90Yetrium- DOTA- conjugated peptides) in the treatment of pancreatic neuroendocrine tumours as a standalone entity or as a subgroup within the wider category of Gastroenteropancreatic Neuroendocrine Tumours (GEP NETs). Results: PRRT was found to be an effective treatment modality as a monotherapy or in combination with other therapies in the treatment of non-operable and metastatic pNETs where other options are limited. Complete response was reported to be between 2-6% while partial response was achieved in up to 60% of cases. Survival analysis was also impressive. Progression Free Survival (PFS) reached a mean of 34 months and Overall Survival (OS) of 53 months. PRRT also proved to improve patients’ Quality of Life (QoL). Acute and sub-acute side effects like nephrotoxicity and haematotoxicity are usually mild and reversible. Conclusion: PRRT is well tolerated and effective treatment option for non-operable and/or metastatic pNETs. Side effects are usually mild and reversible. Larger randomized controlled trails need to be done to compare PRRT with other treatment modalities and to provide more detailed guidelines regarding patient selections, the choice of PRRT, follow up and response assessment to maximum potential benefit.

scholarly journals Molecular profiling of neuroendocrine tumours to predict response and toxicity to peptide receptor radionuclide therapy

2020 ◽  
Vol 21 (9) ◽  
pp. e431-e443 ◽  
Author(s):  
Lisa Bodei ◽  
Heiko Schöder ◽  
Richard P Baum ◽  
Ken Herrmann ◽  
Jonathan Strosberg ◽  
...  
Keyword(s):  
Radionuclide Therapy ◽  
Neuroendocrine Tumours ◽  
Peptide Receptor Radionuclide Therapy ◽  
Molecular Profiling ◽  
Peptide Receptor

scholarly journals Intraindividual comparison of [177Lu]Lu-DOTA-EB-TATE and [177Lu]Lu-DOTA-TOC

2021 ◽  
Author(s):  
Heribert Hänscheid ◽  
Philipp E. Hartrampf ◽  
Andreas Schirbel ◽  
Andreas K. Buck ◽  
Constantin Lapa
Keyword(s):  
Radionuclide Therapy ◽  
Therapeutic Agent ◽  
Somatostatin Receptor ◽  
Absorbed Dose ◽  
Peptide Receptor Radionuclide Therapy ◽  
Somatostatin Analogue ◽  
Target Tissue ◽  
Peptide Receptor ◽  
Intraindividual Comparison ◽  
Administered Activity

Abstract Purpose The radiolabelled somatostatin analogue [177Lu]Lu-DOTA-EB-TATE binds to albumin via Evans blue, thereby increasing the residence time in the blood and potentially allowing more therapeutic agent to be absorbed into the target tissue during peptide receptor radionuclide therapy. It was tested in selected patients whether the substance is superior to [177Lu]Lu-DOTA-TOC. Methods Activity kinetics in organs and tumours after [177Lu]Lu-DOTA-EB-TATE and [177Lu]Lu-DOTA-TOC were compared intraindividually in five patients with progressive somatostatin receptor-positive disease scheduled for radionuclide therapy. Results In comparison to [177Lu]Lu-DOTA-TOC, tumour doses per administered activity were higher for [177Lu]Lu-DOTA-EB-TATE in 4 of 5 patients (median ratio: 1.7; range: 0.9 to 3.9), kidney doses (median ratio: 3.2; range: 1.6 to 9.8) as well as spleen doses (median ratio: 4.7; range 1.2 to 6.2) in all patients, and liver doses in 3 of 4 evaluable patients (median ratio: 4.0; range: 0.7 to 4.9). The tumour to critical organs absorbed dose ratios were higher after [177Lu]Lu-DOTA-TOC in 4 of 5 patients. Conclusions Prior to a treatment with [177Lu]Lu-DOTA-EB-TATE, it should be assessed individually whether the compound is superior to established substances.

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