scholarly journals Peptide Receptor Radionuclide Therapy Targeting the Somatostatin Receptor: Basic Principles, Clinical Applications and Optimization Strategies

Cancers ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 129
Author(s):  
Niloefar Ahmadi Bidakhvidi ◽  
Karolien Goffin ◽  
Jeroen Dekervel ◽  
Kristof Baete ◽  
Kristiaan Nackaerts ◽  
...  
Keyword(s):  
Radionuclide Therapy ◽  
Specific Binding ◽  
Controlled Trial ◽  
Symptom Relief ◽  
Somatostatin Receptor ◽  
Peptide Receptor Radionuclide Therapy ◽  
Molecular Therapy ◽  
Dose Effect ◽  
Molecular Testing ◽  
Peptide Receptor

Peptide receptor radionuclide therapy (PRRT) consists of the administration of a tumor-targeting radiopharmaceutical into the circulation of a patient. The radiopharmaceutical will bind to a specific peptide receptor leading to tumor-specific binding and retention. The only target that is currently used in clinical practice is the somatostatin receptor (SSTR), which is overexpressed on a range of tumor cells, including neuroendocrine tumors and neural-crest derived tumors. Academia played an important role in the development of PRRT, which has led to heterogeneous literature over the last two decades, as no standard radiopharmaceutical or regimen has been available for a long time. This review provides a summary of the treatment efficacy (e.g., response rates and symptom-relief), impact on patient outcome and toxicity profile of PRRT performed with different generations of SSTR-targeting radiopharmaceuticals, including the landmark randomized-controlled trial NETTER-1. In addition, multiple optimization strategies for PRRT are discussed, i.e., the dose–effect concept, dosimetry, combination therapies (i.e., tandem/duo PRRT, chemoPRRT, targeted molecular therapy, somatostatin analogues and radiosensitizers), new radiopharmaceuticals (i.e., SSTR-antagonists, Evans-blue containing vector molecules and alpha-emitters), administration route (intra-arterial versus intravenous) and response prediction via molecular testing or imaging. The evolution and continuous refinement of PRRT resulted in many lessons for the future development of radionuclide therapy aimed at other targets and tumor types.

scholarly journals Case Series of Metastatic VIPoma With Partial Response to Somatostatin Receptor Ligand and Review of Therapeutic Options

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A993-A993
Author(s):  
Lim Sue Wen ◽  
Goh Kian Guan ◽  
Jin Hui Ho ◽  
Serena Sert Kim Khoo ◽  
Zanariah Hussein
Keyword(s):  
Targeted Therapy ◽  
Disease Control ◽  
Radionuclide Therapy ◽  
Symptom Relief ◽  
Somatostatin Receptor ◽  
Case Series ◽  
Peptide Receptor Radionuclide Therapy ◽  
Cytotoxic Chemotherapy ◽  
Peptide Receptor ◽  
Secretory Diarrhoea

Abstract Background: Vasoactive intestinal polypeptide secreting islet cell tumors (VIPoma) are rare neuroendocrine tumors of pancreatic origin, characterized by secretory diarrhoea and electrolyte imbalances. Metastasis, commonly hepatic, frequently occur at diagnosis in up to 80% patients. Surgery of the primary tumour remains the gold standard management and in metastatic tumors, somatostatin receptor ligands (SRL) are the drugs of choice for symptom relief and disease control. Some patients will require other approaches to control symptoms, such as liver-targeted therapy, peptide receptor radionuclide therapy (PRRT) or chemotherapy. We describe a case series of metastatic VIPoma which partially-responded to SRL and review of other treatment modalities to achieve disease and symptom control. Case: We report 3 cases, ages 37 to 58 years, with metastatic VIPoma whom presented with secretory diarrhoea, hypokalaemia, achlorhydria and elevated serum VIP levels. CT and 68Gallium PET-CT imaging identified metastases in liver, bone, lungs, spleen and lymph nodes. One case underwent distal pancreatectomy and splenectomy at diagnosis and two cases were advanced and non-resectable. All received long-acting SRL initially and achieved partial control of the gastrointestinal symptoms. Two cases underwent Peptide Receptor Radionuclide Therapy (PRRT) and one case received cytotoxic chemotherapy. Two patients have progressive disease and one succumbed to advanced disease. For inoperable disease, PRRT is useful adjuvant therapy for symptom relief and may improve progression free survival (PFS). Cytotoxic chemotherapy is an option for patients with progressive or symptomatic unresectable tumor. Chemoembolization or liver-targeted therapy are used in liver metastasis for loco-regional control. Alfa-interferon and targeted therapies such as everolimus and sunitinib are other treatment options that can be considered. Conclusion: Metastatic VIPoma remains a challenging disease to manage, requiring multimodal treatment approaches. With timely diagnosis and advancing therapeutic options, more patients can achieve improved symptom and disease control as well as increased survival.

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 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 

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.

scholarly journals Inter and intra-tumor somatostatin receptor 2 heterogeneity influences peptide receptor radionuclide therapy response

Theranostics ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 491-505
Author(s):  
Danny Feijtel ◽  
Gabriela N. Doeswijk ◽  
Nicole S. Verkaik ◽  
Joost C. Haeck ◽  
Daniela Chicco ◽  
...  
Keyword(s):  
Radionuclide Therapy ◽  
Somatostatin Receptor ◽  
Therapy Response ◽  
Peptide Receptor Radionuclide Therapy ◽  
Peptide Receptor

Neuroradiological and Neuropathological Changes After 177Lu-Octreotate Peptide Receptor Radionuclide Therapy of Refractory Esthesioneuroblastoma

2018 ◽  
Vol 15 (6) ◽  
pp. 100-109 ◽  
Author(s):  
Julia R Schneider ◽  
Deborah R Shatzkes ◽  
Stephen C Scharf ◽  
Tristan M Tham ◽  
Kay O Kulason ◽  
...  
Keyword(s):  
Radionuclide Therapy ◽  
Therapeutic Option ◽  
Somatostatin Receptor ◽  
Malignant Neoplasm ◽  
Peptide Receptor Radionuclide Therapy ◽  
Olfactory Neuroblastoma ◽  
Somatostatin Analogues ◽  
Symptomatic Improvement ◽  
Peptide Receptor ◽  
Molecular Alterations

Abstract BACKGROUND AND IMPORTANCE Olfactory neuroblastoma, also known as esthesioneuroblastoma (ENB), is a malignant neoplasm with an unpredictable behavior. Currently, the widely accepted treatment is inductive chemotherapy, with or without surgery, followed by radiotherapy. Since data on genetics and molecular alterations of ENB are lacking, there is no standard molecularly targeted therapy. However, ENB commonly expresses the somatostatin receptor (SSTR) that is also expressed by neuroendocrine tumors. Peptide receptor radionuclide therapy (PRRT) using radiolabeled somatostatin analogues, such as 177Lu-octreotate, is an effective treatment for the latter. We present the complex neuroradiological and neuropathological changes associated with 177Lu-octreotate treatment of a patient with a highly treatment-resistant ENB. CLINICAL PRESENTATION A 60-yr-old male presented with an ENB that recurred after chemotherapy, surgery, stereotactic radiosurgery, and immunotherapy. Pathology revealed a Hyams grade 3 ENB and the tumor had metastasized to lymph nodes. Tumor SSTR expression was seen on 68Ga-octreotate positron emission tomography (PET)/computed tomography (CT), suggesting that PRRT may be an option. He received 4 cycles of 177Lu-octreotate over 6 mo, with a partial response of all lesions and symptomatic improvement. Four months after the last PRRT cycle, 2 of the lesions rapidly relapsed and were successfully resected. Three months later, 68Ga-octreotate PET/CT and magnetic resonance imaging indicate no progression of the disease. CONCLUSION We describe imaging changes associated with 177Lu-octreotate PRRT of relapsing ENB. To our knowledge, this is the first report describing neuropathological changes associated with this treatment. PRRT is a promising therapeutic option to improve the disease control, and potentially, the survival of patients with refractory ENB.

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