scholarly journals Functional Imaging and Peptide Receptor Radionuclide Therapy for Pancreatic Neuroendocrine Tumor

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.

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.


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.


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

2017 ◽  
Vol 42 (6) ◽  
pp. 436-443 ◽  
Author(s):  
Mohammadali Hamiditabar ◽  
Muzammil Ali ◽  
Joseph Roys ◽  
Edward M. Wolin ◽  
Thomas M. OʼDorisio ◽  
...  

2011 ◽  
Vol 152 (10) ◽  
pp. 392-397 ◽  
Author(s):  
Péter Reismann ◽  
Zoltán Kender ◽  
Gabriella Dabasi ◽  
Lídia Sréter ◽  
Károly Rácz ◽  
...  

Beside conventional therapies for the treatment of neuroendocrine tumors, a new therapeutical approach, peptide receptor radionuclide therapy has been developed recently. There are two important features which make this therapy feasible: somatostatin receptors are strongly over-expressed in most neuroendocrine tumors resulting in a high tumor-to-background ratio and internalization of the somatostatin-receptor complex in neuroendocrine cells. Due to these features, neuroendocrine tumors can be treated with radiolabelled somatostatin analogues. For peptide receptor radionuclide therapy, somatostatin analogues are conjugated to a chelator that can bind a radionuclide. The most frequently used radionuclides for neuroendocrine tumor treatment are the β-emitter Yttrium-90 (90Y) and the β+γ emitter Lutetium-177 (177Lu). Candidates for somatostatin receptor endoradiotherapy are patients with progressive, metastatic, somatostatin-receptor positive neuroendocrine tumors. Many patients have been successively treated with this approach: according to international results major remission can be achieved in 25% of the cases. Although this therapy is still unavailable in Hungary, Hungarian patients can be treated with somatostatin receptor endoradiotherapy with financial support from the National Health Fund in a co-operation with the University of Basel since 2005. During the past 5 years, 51 Hungarian patients have been treated with this therapy. This review briefly summarizes the theoretical background, indications, effectiveness and side effects of somatostatin receptor endoradiotherapy and the authors present the first data obtained from Hungarian patients. Orv. Hetil., 2011, 152, 392–397.


2019 ◽  
Vol 12 (1) ◽  
pp. 98-103 ◽  
Author(s):  
Pashtoon M. Kasi ◽  
Akash Sharma ◽  
Manoj K. Jain

The field of theranostics is a new nuclear medicine tool being utilized in the treatment of different types of cancers. It couples receptor-specific based imaging predicting and guiding response to receptor-specific based radionuclide therapies. For example, somatostatin-receptor based imaging (Gallium; 68Ga-dotatate scan) is now predicting and guiding the use of treatment with the somatostatin-receptor radiolabeled somatostatin analog (peptide receptor radionuclide therapy PRRT – Lutetium; 177Lu-Dotatate) for neuroendocrine tumors that express the somatostatin receptors. The United States Food and Drug Administration approved the use of 177Lu-Dotatate PRRT for somatostatin-receptor-positive gastroenteropancreatic neuroendocrine tumors only. Here we show proof of concept and results of an outstanding response to this novel therapy in conjunction with immunotherapy in a refractory cancer type where it has not been approved (Merkel Cell Cancer). Our results and data provide proof of principle for considering the use of this novel therapy in a tumor-agnostic approach; similar to approval of immunotherapy for mismatch repair deficient tumors. The response demonstrated has also been unprecedented, likely secondary to use of PRRT with immunotherapy. These observations have profound and broad implications on how to move this novel field of theranostics forward for treatment of many cancer-types.


2021 ◽  
Vol 5 (1) ◽  
Author(s):  
Sander C. Ebbers ◽  
Muriël Heimgartner ◽  
Maarten W. Barentsz ◽  
Rachel S. van Leeuwaarde ◽  
Mark J. C. van Treijen ◽  
...  

Abstract Background Early [68Ga]Ga-DOTA-TOC PET/CT imaging after peptide receptor radionuclide therapy (PRRT) in neuroendocrine neoplasm patients is often used as a prognosticator for survival, but lacks validity. This study investigates the prognostic value of changes in PET parameters after PRRT. Methods Baseline and follow-up [68Ga]Ga-DOTA-TOC PET/CT scans of all patients treated with PRRT were delineated automatically. Total lesion somatostatin receptor expression (TL-SSTR) and somatostatin receptor expressing tumor volume (SSTR-TV) were used as covariates in Cox proportional hazard models to predict time-to-new treatment. Results In twenty patients, median time-to-new treatment was 19.3 months (range [3.8; 36.2]). Absolute and percentual changes in both PET parameters were not associated with time-to-new treatment. A significant relation between independent baseline and follow-up SSTR-TV and follow-up TL-SSTR, and time-to-new treatment was identified. Conclusions Automatically derived [68Ga]Ga-DOTA-TOC PET/CT parameters are easy to acquire and may be of prognostic value after completing PRRT. Acquiring SSTR-TV or TL-SSTR parameters at baseline and during follow-up can be of value in identifying a patient’s prognosis.


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