scholarly journals Gastroenteropancreatic Neuroendocrine Tumors: Standardizing Therapy Monitoring with68Ga-DOTATOC PET/CT Using the Example of Somatostatin Receptor Radionuclide Therapy

2010 ◽  
Vol 9 (6) ◽  
pp. 7290.2010.00035 ◽  
Author(s):  
Wolfgang Luboldt ◽  
Holger Hartmann ◽  
Bärbel Wiedemann ◽  
Klaus Zöphel ◽  
Hans-Joachim Luboldt
2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
Sowon Oh ◽  
Vikas Prasad ◽  
Dong Soo Lee ◽  
R. P. Baum

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.


2021 ◽  
Vol 26 (1) ◽  
pp. 10-14
Author(s):  
Keon Wook Kang

Somatostatin receptors (SSTR) are overexpressed in various tumors including neuroendocrine tumors. In-111 Octreoscan or Ga-68 DOTATOC positron emission tomography/computed tomography (PET/CT) showed these SSTR expressing tumors in whole body of patients. Ga-68 DOTATOC PET/CT has a better sensitivity and resolution than In-111 Octreoscan with single photon emission computed tomography (SPECT)/CT.. The indications of Ga-68 DOTATOC PET/CT are 1) staging: detect sites of primary and metastasis, 2) re-staging: follow-up of patients with known disease to detect residual, recurrent or progressive disease, 3) prognosis & management decisions: determine SSTR status & select patients with SSTR radionuclide therapy, and 4) monitor the response to therapy. Nuclear medicine treatments for neuroendocrine tumors with radioisotope labeling on the somatostatin receptor targeting peptide (peptide receptor radionuclide therapy, PRRT) were conducted in Europe, Australia, and other countries for over 20 years. Eligible patients to be effective to PRRT using Lu-177 DOTATATE can be pre-screened by confirming the expression of somatostatin receptor on tumors using Octreoscan or Ga-68 DOTATOC PET/CT prior to treatment. This pair of molecular targeted treatment and companion diagnostics, so called molecular theranostics makes PRRT a good example for a precision medicine. A multinational clinical trial with the Lu-177 DOTATATE treatment (Lutathera) showed a significant progression free survival over the control group and Ministry of Food and Drug Safety in Korea approved Lutathera. Some doctors are treating patients who are refractory to Lu-177 using Ac-225, an alpha-emitter therapy in Germany and India. The high therapeutic effect of the alpha emitting radionuclides will lead the future of nuclear medicine therapy.


2019 ◽  
Vol 03 (01) ◽  
pp. 071-080
Author(s):  
Ghassan El-Haddad

AbstractPeptide receptor radionuclide therapy (PRRT), a targeted form of systemic radiotherapy allowing the delivery of radionuclides directly to tumor cells, has been used for more than three decades in the treatment of advanced neuroendocrine tumors (NETs) exhibiting high levels of somatostatin receptors. Recently, 177Lu-DOTATATE, a radiolabeled somatostatin analog, was approved by the US Food and Drug administration for the treatment of somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs) in adults. Early phase I and II studies have shown the benefits of PRRT, but it was the NETTER-1 trial (a large-scale randomized multicenter trial for progressive well-differentiated advanced or metastatic somatostatin receptor-positive midgut carcinoid tumors) that provided high-level evidence of improved overall response rate, and progression-free survival compared with long-acting octreotide. In this article, we will discuss the evolution, clinical applications, and implementation of PRRT, as well as potential future strategies to enhance its clinical efficacy in the treatment of GEP-NETs.


Diagnostics ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 504
Author(s):  
Fiona Ohlendorf ◽  
Rudolf Werner ◽  
Christoph Henkenberens ◽  
Tobias Ross ◽  
Hans Christiansen ◽  
...  

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.


Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1516
Author(s):  
Thorsten Derlin ◽  
Natalia Bogdanova ◽  
Fiona Ohlendorf ◽  
Dhanya Ramachandran ◽  
Rudolf A. Werner ◽  
...  

Background: We aimed to characterize γ-H2AX and 53BP1 foci formation in patients receiving somatostatin receptor-targeted radioligand therapy, and explored its role for predicting treatment-related hematotoxicity, and treatment response. Methods: A prospective analysis of double-strand break (DSB) markers was performed in 21 patients with advanced gastroenteropancreatic neuroendocrine tumors. γ-H2AX and 53BP1 foci formation were evaluated in peripheral blood lymphocytes (PBLs) at baseline, +1 h and +24 h after administration of 7.4 GBq (177Lu)Lu-DOTA-TATE. Hematotoxicity was evaluated using standard hematology. Therapy response was assessed using (68Ga)Ga-DOTA-TATE PET/CT before enrollment and after 2 cycles of PRRT according to the volumetric modification of RECIST 1.1. Results: DSB marker kinetics were heterogeneous among patients. Subclinical hematotoxicity was associated with γ-H2AX and 53BP1 foci formation (e.g., change in platelet count vs change in γ-H2AX+ cells between baseline and +1 h (r = −0.6080; p = 0.0045). Patients showing early development of new metastases had less γ-H2AX (p = 0.0125) and less 53BP1 foci per cell at +1 h (p = 0.0289), and demonstrated a distinct kinetic pattern with an absence of DSB marker decrease at +24 h (γ-H2AX: p = 0.0025; 53BP1: p = 0.0008). Conclusions: Assessment of γ-H2AX and 53BP1 foci formation in PBLs of patients receiving radioligand therapy may hold promise for predicting subclinical hematotoxicity and early treatment response.


Pancreas ◽  
2014 ◽  
Vol 43 (4) ◽  
pp. 518-525 ◽  
Author(s):  
Ebrahim S. Delpassand ◽  
Amin Samarghandi ◽  
Sara Zamanian ◽  
Edward M. Wolin ◽  
Mohammadali Hamiditabar ◽  
...  

2021 ◽  
Vol 8 ◽  
Author(s):  
Jiale Hou ◽  
Yi Yang ◽  
Na Chen ◽  
Dengming Chen ◽  
Shuo Hu

Purpose: A meta-analysis was conducted to investigate the value of the volume parameters based on somatostatin receptor (SSTR)-positron emission tomography (PET) in predicting the prognosis in patients with neuroendocrine tumors (NETs).Material: PUBMED, EMBASE, Cochrane library, and Web of Knowledge were searched from January 1990 to May 2021 for studies evaluating prognostic value of volume-based parameters of SSTR PET/CT in NETs. The terms used were “volume,” “positron emission tomography,” “neuroendocrine tumors,” and “somatostatin receptor.” Pooled hazard ratio (HR) values were calculated to assess the correlations between volumetric parameters, including total tumor volume (TTV) and total-lesion SSTR expression (TL-SSTR), with progression-free survival (PFS) and overall survival (OS). Heterogeneity and subgroup analysis were performed. Funnel plots, Begg's and Egger's test were used to assess possible underlying publication bias.Results: Eight eligible studies involving 593 patients were included in the meta-analysis. In TTV, the pooled HRs of its prognostic value of PFS and OS were 2.24 (95% CI: 1.73–2.89; P &lt; 0.00001) and 3.54 (95% CI, 1.77–7.09; P = 0.0004), respectively. In TL-SSTR, the pooled HR of the predictive value was 1.61 (95% CI, 0.48–5.44, P = 0.44) for PFS.Conclusion: High TTV was associated with a worse prognosis for PFS and OS in with patients NETs. The TTV of SSTR PET is a potential objective prognosis predictor.


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