Peptide receptor radionuclide therapy (PRRT) for GEP-NETs

Bergsma, Hendrik; Vliet, Esther I. van; Teunissen, Jaap J.M.; Kam, Boen L.R.; Herder, Wouter W. de; Peeters, Robin P.; Krenning, Eric P.; Kwekkeboom, Dik J.

doi:10.1016/j.bpg.2013.01.004

Cited by 58 publications

(43 citation statements)

References 52 publications

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“…Somatostatin analog treatment was continued in all patients during treatment with everolimus in our study. All patients received treatment with 177 Lu-octreotate and it is commonly known that with this therapy high cumulative dosages can cause serious side effects, including kidney failure, cytopenias, or myelodysplastic syndrome (MDS; Bergsma et al 2012). With this knowledge, drug-related kidney failure was monitored in this study.…”

Section: Discussionmentioning

confidence: 99%

“…With this knowledge, drug-related kidney failure was monitored in this study. However, data from the Rotterdam 177 Lu-octreotate trial show that serious hematological toxicity, MDS, and liver toxicity are relatively rare and occur in w1% of the patients (Kwekkeboom et al 2008, van Essen et al 2010. Everolimus therapy can be associated with mild lymphopenia and neutropenia.…”

Section: Discussionmentioning

confidence: 99%

“…However, upon progression, peptide receptor radionuclide therapy (PRRT) with radiolabeled somatostatin analogs has been shown to be effective regarding tumor control (Bergsma et al 2012). Although 177 Lu-octreotate is being increasingly used, there are limitations to its use and some patients who initially responded may became refractory after a certain number of treatment cycles necessitating further treatment.…”

Section: Introductionmentioning

confidence: 99%

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Safety and efficacy of everolimus in gastrointestinal and pancreatic neuroendocrine tumors after 177Lu-octreotate

Kamp¹,

Gumz²,

Feelders³

et al. 2013

Endocrine-Related Cancer

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Safety and efficacy of everolimus in gastrointestinal and pancreatic neuroendocrine tumors after 177Lu-octreotate

Kamp¹,

Gumz²,

Feelders³

et al. 2013

Endocrine-Related Cancer

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“…These SST analogs have been coupled to different chelators, enabling labeling of the SST analogs with positron emitters, such as 68 Ga for PET scanning, and b-emitters, such as 90 Y and 177 Lu for therapeutic purposes, leading to better imaging and therapy results. Concerning therapy, response rates between 10% and 35% have been reported after treatment of gastroenteropancreatic neuroendocrine tumors using 90 Y-DOTATOC or 177 Lu-DOTA-octreotate (2,3). Although results are positive, there is room for improvement of PRRT using SSTR radioligands.…”

mentioning

confidence: 99%

Comparison of the Therapeutic Response to Treatment with a ¹⁷⁷Lu-Labeled Somatostatin Receptor Agonist and Antagonist in Preclinical Models

et al. 2015

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Peptide receptor scintigraphy and peptide receptor radionuclide therapy using radiolabeled somatostatin receptor (SSTR) agonists are successfully used in the clinic for imaging and treatment of neuroendocrine tumors. Contrary to the paradigm that internalization and the resulting accumulation of radiotracers in cells is necessary for efficient tumor targeting, recent studies have demonstrated the superiority of radiolabeled SSTR antagonists for imaging purposes, despite little to no internalization in cells. However, studies comparing the therapeutic antitumor effects of radiolabeled SSTR agonists versus antagonists are lacking. The aim of this study was to directly compare the therapeutic effect of 177 Lu-DOTA-octreotate, an SSTR agonist, and 177 Lu-DOTA-JR11, an SSTR antagonist. Methods: We analyzed radiotracer uptake (both membrane-bound and internalized fractions) and the produced DNA double-strand breaks, by determining the number of p53 binding protein 1 foci, after incubating SSTR2-positive cells with 177 Lu-diethylene triamine pentaacetic acid, 177 Lu-DOTA-octreotate, or 177 Lu-DOTA-JR11. Also, biodistribution studies were performed in tumor-xenografted mice to determine the optimal dose for therapy experiments. Afterward, in vivo therapy experiments comparing the effect of 177 Lu-DOTA-octreotate and 177 Lu-DOTA-JR11 were performed in this same animal model. Results: We found a 5-times-higher uptake of 177 Lu-DOTA-JR11 than of 177 Lu-DOTA-octreotate. The major part (88% ± 1%) of the antagonist uptake was membranebound, whereas 74% ± 3% of the total receptor agonist uptake was internalized. Cells treated with 177 Lu-DOTA-JR11 showed 2 times more p53-binding protein 1 foci than cells treated with 177 Lu-DOTAoctreotate. Biodistribution studies with 177 Lu-DOTA-JR11 (0.5 μg/ 30 MBq) resulted in the highest tumor radiation dose of 1.8 ± 0.7 Gy/ MBq, 4.4 times higher than the highest tumor radiation dose found for 177 Lu-DOTA-octreotate. In vivo therapy studies with 177 Lu-DOTAoctreotate and 177 Lu-DOTA-JR11 resulted in a tumor growth delay time of 18 ± 5 and 26 ± 7 d, respectively. Median survival rates were 43.5, 61, and 71 d for the control group, 177 Lu-DOTA-octreotate group, and the 177 Lu-DOTA-JR11-treated group, respectively. Conclusion: On the basis of these results, we concluded that the use of radiolabeled SSTR antagonists such as JR11 might enhance peptide receptor scintigraphy and peptide receptor radionuclide therapy of neuroendocrine tumors and provide successful imaging and therapeutic strategies for cancer types with relatively low SSTR expression. Radi olabeled somatostatin (SST) analogs targeting SST receptors (SSTRs), especially SSTR2, overexpressed on tumor cells are successfully used for imaging and treatment of neuroendocrine tumors. These applications are referred to as peptide receptor scintigraphy (PRS) and peptide receptor radionuclide therapy (PRRT), respectively. PRS using radiolabeled SST analogs was first described in the late 1980s by Krenning et al. (1), and soon after the first...

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“…These symptoms can be controlled by agents directed towards somatostatin (SST) receptors which are over expressed in 80-85 % of well to moderately differentiated NETs [6][7][8]. The available agonists against these receptors have an "excellent" effect on the symptom control, by inhibiting the release of bioactive agents and exhibit a relatively good therapeutic index [9].…”

Section: Introductionmentioning

confidence: 99%

Whither peptide receptor radionuclide therapy for neuroendocrine tumors: an Einsteinian view of the facts and myths

Prasad

Bodei

Kidd

et al. 2014

Eur J Nucl Med Mol Imaging

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Peptide receptor radionuclide therapy (PRRT) for GEP-NETs

Cited by 58 publications

References 52 publications

Safety and efficacy of everolimus in gastrointestinal and pancreatic neuroendocrine tumors after 177Lu-octreotate

Safety and efficacy of everolimus in gastrointestinal and pancreatic neuroendocrine tumors after 177Lu-octreotate

Comparison of the Therapeutic Response to Treatment with a ¹⁷⁷Lu-Labeled Somatostatin Receptor Agonist and Antagonist in Preclinical Models

Whither peptide receptor radionuclide therapy for neuroendocrine tumors: an Einsteinian view of the facts and myths

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Peptide receptor radionuclide therapy (PRRT) for GEP-NETs

Cited by 58 publications

References 52 publications

Safety and efficacy of everolimus in gastrointestinal and pancreatic neuroendocrine tumors after 177Lu-octreotate

Safety and efficacy of everolimus in gastrointestinal and pancreatic neuroendocrine tumors after 177Lu-octreotate

Comparison of the Therapeutic Response to Treatment with a 177Lu-Labeled Somatostatin Receptor Agonist and Antagonist in Preclinical Models

Whither peptide receptor radionuclide therapy for neuroendocrine tumors: an Einsteinian view of the facts and myths

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Comparison of the Therapeutic Response to Treatment with a ¹⁷⁷Lu-Labeled Somatostatin Receptor Agonist and Antagonist in Preclinical Models