Phase 1/2 open-label trial to assess the safety and preliminary efficacy of 177Lu-OPS201 as peptide receptor radionuclide therapy in patients with somatostatin receptor-positive, progressive neuroendocrine tumours

2017 ◽  
Author(s):  
Guillaume Nicolas ◽  
Richard Baum ◽  
Ken Herrmann ◽  
Michael Lassmann ◽  
Rodney Hicks ◽  
...  
Keyword(s):  
Radionuclide Therapy ◽  
Neuroendocrine Tumours ◽  
Phase 1 ◽  
Somatostatin Receptor ◽  
Peptide Receptor Radionuclide Therapy ◽  
Open Label ◽  
Peptide Receptor ◽  
Open Label Trial

scholarly journals RADIONUCLIDE IMAGING AND THERAPY OF NEUROENDOCRINE TUMOURS

2015 ◽  
Vol 1 (2) ◽  
Author(s):  
Shaunak Navalkissoor ◽  
Gopinath Gnanasegaran
Keyword(s):  
Radionuclide Imaging ◽  
Radionuclide Therapy ◽  
Neuroendocrine Tumours ◽  
Somatostatin Receptor ◽  
Peptide Receptor Radionuclide Therapy ◽  
Clinical Results ◽  
It Use ◽  
Peptide Receptor ◽  
Mibg Therapy

The incidence and prevalence of neuroendocrine tumours (NETs) are on the rise. Although NETs are a heterogeneous group of tumours, they have some similar properties, for example, that they can concentrate neuroamines and tend to have a high degree of somatostatin receptor (SSR) expression. These mechanisms can be exploited and this article discusses the important role of radionculide imaging and radionculide therapy in the management of NETs based on these mechanisms. This article reviews the current literature and discusses the role of radionuclide imaging in NETs both in terms of SSR imaging and neuroamine (metaiodobenzylguanidine [MIBG]) imaging. We discuss state-of- the-art 68Ga-radiopeptide imaging and indications for it use. We also discuss the role of 18F-FDG and other tracers in the management of NETs. The second half of the article focuses on radiotargeted treatment of NETs, discussing I-131 MIBG therapy and focussing on the emergence of peptide receptor radionuclide therapy. We discuss the clinical results, toxicities and patient selection for PRRT. Key words: DOTA octreotide, DOTATATE, Ga-68, Lu-177, metaiodobenzylguanidine, neuroendocrine tumours, peptide receptor radionuclide therapy, Y-90 

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.

scholarly journals Predictive and Prognostic Impact of Blood-Based Inflammatory Biomarkers in Patients with Gastroenteropancreatic Neuroendocrine Tumors Commencing Peptide Receptor Radionuclide Therapy

Diagnostics ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 504
Author(s):  
Fiona Ohlendorf ◽  
Rudolf Werner ◽  
Christoph Henkenberens ◽  
Tobias Ross ◽  
Hans Christiansen ◽  
...  
Keyword(s):  
Treatment Response ◽  
Neuroendocrine Tumors ◽  
Radionuclide Therapy ◽  
Somatostatin Receptor ◽  
Peptide Receptor Radionuclide Therapy ◽  
Tumor Burden ◽  
Inflammatory Biomarkers ◽  
Whole Body ◽  
Prognostic Impact ◽  
Peptide Receptor

Tumor microenvironment inflammation contributes to the proliferation and survival of malignant cells, angiogenesis, metastasis, subversion of adaptive immunity, and reduced treatment response. We aimed to evaluate the early predictive and prognostic significance of markers of systemic inflammation in patients receiving somatostatin-receptor targeted peptide receptor radionuclide therapy (PRRT). This retrospective observational cohort study included 33 patients with advanced gastro-entero-pancreatic neuroendocrine tumors (GEP-NETs) treated with PRRT. Pretreatment blood-based inflammatory biomarkers, e.g., Creactive protein levels (CRP), white blood cell count (WBC), and absolute neutrophil count (ANC), were documented and inflammation indexes, e.g., neutrophil-lymphocyte ratio (NLR) and Platelet × CRP multiplier (PCM), were calculated. Tumor burden was determined using [68Ga]GaDOTATATE PET/CT before enrollment and every 2 cycles thereafter until progression. Therapy response was assessed using RECIST 1.1, including its volumetric modification. Inflammatory biomarkers and inflammatory indexes demonstrated marked heterogeneity among patients, and were significantly higher in non-responders (e.g., CRP (P < 0.001), ANC (P = 0.002), and PCM (P < 0.001)). Change in whole-body tumor burden after two cycles of PRRT was significantly associated with CRP (P = 0.0157) and NLR (P = 0.0040) in multivariate regression analysis. A cut-off of 2.5 mg/L for CRP (AUC = 0.84, P = 0.001) revealed a significant outcome difference between patients with adversely high vs. low CRP (median PFS 508 days vs. not yet reached (HR = 4.52; 95% CI, 1.27 to 16.18; P = 0.02)). Tumor-driven systemic inflammatory networks may be associated with treatment response, change in tumor burden, and prognosis in patients with GEPNETs receiving PRRT.

Peptide Receptor Radionuclide Therapy With 177Lu-DOTATATE for Patients With Somatostatin Receptor–Expressing Neuroendocrine Tumors

Pancreas ◽  
2014 ◽  
Vol 43 (4) ◽  
pp. 518-525 ◽  
Author(s):  
Ebrahim S. Delpassand ◽  
Amin Samarghandi ◽  
Sara Zamanian ◽  
Edward M. Wolin ◽  
Mohammadali Hamiditabar ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Radionuclide Therapy ◽  
Somatostatin Receptor ◽  
Peptide Receptor Radionuclide Therapy ◽  
Peptide Receptor

scholarly journals Effect of Peptide Receptor Radionuclide Therapy on Somatostatin Receptor Status and Glucose Metabolism in Neuroendocrine Tumors: Intraindividual Comparison of Ga-68 DOTANOC PET/CT and F-18 FDG PET/CT

2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
Sowon Oh ◽  
Vikas Prasad ◽  
Dong Soo Lee ◽  
R. P. Baum
Keyword(s):  
Glucose Metabolism ◽  
Neuroendocrine Tumors ◽  
Fdg Pet ◽  
Radionuclide Therapy ◽  
Somatostatin Receptor ◽  
Peptide Receptor Radionuclide Therapy ◽  
Receptor Expression ◽  
Peptide Receptor ◽  
Pet Ct ◽  
Fdg Pet Ct

The heterogeneous nature of the neuroendocrine tumors (NET) makes it challenging to find one uniformly applicable management protocol which is especially true for diagnosis. The discovery of the overexpression of somatostatin receptors (SMS-R) on neuroendocrine tumor cells lead to the generalized and rapid acceptance of radiolabeled somatostatin receptor analogs for staging and restaging of NET as well as for Peptide Receptor Radionuclide Therapy (PRRNT) using Y-90 and Lu-177 DOTATATE/DOTATOC. In this present work we tried to look in to the effect of PRRNT on the glucose metabolism assessed by F-18 FDG PET/CT and SMS-R density assessed by Ga-68 DOTANOC PET/CT. We observed a complex relationship between the somatostatin receptor expression and glucose metabolism with only 56% (77/138) of the lesions showing match, while the others show mismatch between the receptor status and metabolism. The match between receptor expression and glucose metabolism increases with the grade of NET. In grade 3 NET, there is a concurrence between the changes in glucose metabolism and somatostatin receptor expression. PRRNT was found to be more effective in lesions with higher receptor expression.

scholarly journals Somatostatin receptor radionuclide therapy in neuroendocrine tumors

2021 ◽  
Vol 28 (3) ◽  
pp. R81-R93
Author(s):  
Mintallah Haider ◽  
Satya Das ◽  
Taymeyah Al-Toubah ◽  
Eleonora Pelle ◽  
Ghassan El-Haddad ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Radionuclide Therapy ◽  
Somatostatin Receptor ◽  
Somatostatin Analogs ◽  
Peptide Receptor Radionuclide Therapy ◽  
Study Data ◽  
Combination Therapies ◽  
Peptide Receptor ◽  
Therapeutic Landscape ◽  
Receptor Agonists And Antagonists

Peptide receptor radionuclide therapy (PRRT) using 177Lu-DOTATATE has been approved for the treatment of gastroenteropancreatic NETs. An understanding of benefits and risks is important for the appropriate implementation of this therapy. This review summarizes study data supporting the use of radiolabeled somatostatin analogs for the treatment of advanced NETs and highlights risks, including potential toxicities in specific populations. Key ongoing clinical trials, including randomized studies, are designed to better define the position of PRRT within the broader therapeutic landscape. Preclinical and early-phase human studies are focused on the development of novel somatostatin-receptor agonists and antagonists, new radionuclides, and radiosensitizing combination therapies.

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