Investigation of receptor radionuclide therapy with 177Lu-DOTATATE in patients with GEP-NEN and a high Ki-67 proliferation index

Nicolini, Silvia; Severi, Stefano; Ianniello, Annarita; Sansovini, Maddalena; Ambrosetti, A.; Bongiovanni, Alberto; Scarpi, Emanuela; Mauro, Francesca Di; Rossi, Alice; Matteucci, Federica; Paganelli, Giovanni

doi:10.1007/s00259-017-3925-8

Cited by 65 publications

(55 citation statements)

References 27 publications

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“…Six of the 13 studies included in Tables 4-6 do not include outcomes of the G3 patients, and only 4 commented on the degree of differentiation. Of the 7 (7/13) studies (29)(30)(31)(32)(33)(34)(35) that directly measured the outcome of the G3 patients, there were a total of 151 patients in whom imaging studies could be tracked over time after receiving PRRT. Of these 151 patients, 99 (66%) demonstrated either stable disease, partial response, or complete response.…”

Section: Therapeuticsmentioning

confidence: 99%

“…Considering the heterogeneity of the data, it is difficult to identify any specific characteristics that may predict response to PRRT in G3 NENs, given that the tumors were located in many different primary sites and the PRRT included a mix of 177 Lu and 29reported significantly better outcomes in patients with a Ki-67 of no more than 55%, similar to the NORDIC study. The data from the study by Nicolini et al (30) include 5 patients with a Ki-67 of between 15% and 20% and 8 patients with a Ki-67 of 20%, but the data do not track disease response from these patients apart from the other 20 patients with a Ki-67 of more than 20%. This factor may explain why the patients reported in their study had an overall better response than in some of the others in Tables 4-6.…”

Section: Therapeuticsmentioning

confidence: 99%

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Evaluating the Role of Theranostics in Grade 3 Neuroendocrine Neoplasms

2019

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The diagnosis and subsequent therapy of neuroendocrine neoplasms (NENs) have long relied on somatostatin receptor (SSTR) expression. The field of theranostics now uses newer SSTR-based PET imaging with 68 Ga-DOTATATE or 68 Ga-DOTATOC as a prerequisite for the administration of peptide receptor radionuclide therapy (PRRT). In the United States, Food and Drug Administration approval of 177 Lu-DOTATATE, a form of PRRT, in 2018 for use in gastroenteropancreatic NENs was obtained on the basis of prolonged progression-free survival versus high-dose octreotide longacting release in a phase III clinical trial of well-differentiated midgut NENs. Well-differentiated grade 1 and grade 2 NENs have a low proliferation index (Ki-67 , 20%) and longer overall survival (.10 y), whereas higher-grade (grade 3 [G3]) NENs have a high Ki-67 (.20%) and shorter overall survival (,1 y). Here, we present a review on the role of SSTR-based imaging and PRRT in G3 NENs, including a discussion of well-differentiated G3 NENs, the newest histologic classification. Some studies suggest that G3 NENs are less likely to be positive on SSTR-based imaging (but more likely on 18 F-FDG PET) than are well-differentiated NENs, but these data are limited. We found only 13 studies mentioning the use of PRRT in G3 NENs and a total of only 151 patients across these studies in whom radiologic response was measured. Of these 151 patients, 99 (66%) demonstrated at least stable disease or a partial response, indicating that some G3 NENs can be responsive to PRRT. We suggest that patients with G3 NENs should receive both 18 F-FDG PET and SSTR-based imaging to aid in both diagnosis and treatment selection, as positivity on SSTR-based imaging helps with patient identification for PRRT and discordance may suggest important clues to tumor biology and prognosis. However, prospective studies are needed to fully understand the role of PRRT in G3 NENs, especially in well-versus poorly differentiated G3 disease.

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Section: Therapeuticsmentioning

confidence: 99%

Section: Therapeuticsmentioning

confidence: 99%

Evaluating the Role of Theranostics in Grade 3 Neuroendocrine Neoplasms

2019

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“…Ein höherer Ki-67-Index war mit einem kürzeren progressionsfreien Überleben verbunden [48]. Während diese Daten vielversprechend für die Anwendung von 177 Lu-DOTA-TATE bei G3-Tumoren sind, zeigte eine andere retrospektive Auswertung eine deutlich niedrigere Ansprechrate [49]. In dieser post-hoc-Analyse von Daten einer Subgruppe von 33 Patienten, die im Rahmen einer prospektiven Phase II-Studie behandelt worden waren, betrug die Ansprechrate nur 6 %.…”

Section: Studieunclassified

“…In dieser post-hoc-Analyse von Daten einer Subgruppe von 33 Patienten, die im Rahmen einer prospektiven Phase II-Studie behandelt worden waren, betrug die Ansprechrate nur 6 %. Das progressionsfreie Überleben war mit 23 Monaten aber wiederum vielversprechend [49]. Es muss auch bedacht werden, dass nur etwa 40 -70 % der G3-neuroendokrinen Tumore eine Überexpression von Somatostatinrezeptoren zeigen und für eine Therapie mit 177 Lu-DOTA-TATE prinzipiell geeignet sind [21].…”

Section: Studieunclassified

Theranostik von neuroendokrinen Tumoren

Bodei

2019

Nuklearmediziner

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ZusammenfassungNeuroendokrine Tumore sind eine heterogene Gruppe von Erkrankungen, die häufig spezifische Rezeptoren, Transporter und Enzyme exprimieren, die für die nuklearmedizinische Bildgebung und Therapie eingesetzt werden können. Insbesondere radioaktiv markierte Liganden der Somatostatinrezeptoren haben sich dabei als effektiv erwiesen. Die medikamentöse Therapie von neuroendokrinen Tumoren ist abhängig vom histologischen Differenzierungsgrad und der Tumorlokalisation. Durch randomisierte Studien wurde die Effektivität von Somatostatinanaloga nicht nur für die Behandlung von Symptomen, sondern auch zur Verlangsamung des Tumorwachstums, nachgewiesen. Der mTOR-Inhibitor Everolimus verlangsamt im Vergleich zu Placebo das Wachstum von neuroendokrinen Tumoren der Lunge, des Pankreas und des Gastrointestinaltrakts. Für den Multikinase-Inhibitor Sunitinib, der die tumorinduzierte Angiogenese hemmt, ist die Wirksamkeit nur für neuroendokrine Tumore des Pankreas nachgewiesen. Im Vergleich zu diesen medikamentösen Therapieansätzen kommt es durch die nuklearmedizinische Therapie mit deutlich höherer Wahrscheinlichkeit zu einem Therapieansprechen und einem längeren progressionsfreien Überleben im Vergleich zu Somatostatinanaloga. Dies wurde kürzlich auch durch eine randomisierte Studie bestätigt, die zur Zulassung von 177Lu-DOTA-TATE in Europa und den USA geführt hat. Eine randomisierte Studie, die 177Lu-DOTA-TOC mit Everolimus vergleicht, rekrutiert derzeit Patienten. Ob die Effektivität der nuklearmedizinischen Therapie durch den Einsatz von Somatostatinrezeptor-Antagonisten weiter gesteigert werden kann, wird ebenfalls in prospektiven Studien untersucht. Die Bedeutung von neuroendokrinen Tumoren für die Nuklearmedizin wird deshalb sehr wahrscheinlich weiter zunehmen.

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“…9 Recently, 177 Lu-PSMA and 177 Lu-DOTA-TATE have been used in prostate cancer and neuroendocrine tumors, respectively, and achieved satisfactory results. [10][11][12][13] DTPA can be easily and efficiently labeled with 177 Lu with high radiochemical purity and stability. 14 Previous studies have shown that DTPA-DG may be used as a radiopharmaceutical agent for tumors.…”

Section: Introductionmentioning

confidence: 99%

Preliminary Studies of ¹⁷⁷Lu-Diethylenetriamine Penta-Acetic Acid-Deoxyglucose in Hepatic Tumor-Bearing Mice

Zhou

Chen

Yang

et al. 2020

Cancer Biotherapy and Radiopharmaceuticals

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Objective: The purpose of this study was to explore the potential use of 177 Lu-diethylenetriamine penta-acetic acid-deoxyglucose (177 Lu-DTPA-DG) as a radiopharmaceutical for hepatic tumor treatment. Methods: Lutetium-177 (177 Lu) was labeled with DTPA-DG by adding 2 mCi 177 LuCl 3 to 0.05 mg DTPA-DG (pH 5-6) at room temperature for 1 h. The quality of the 177 Lu-DTPA-DG solutions was determined by thinlayer chromatography and high-performance liquid chromatography. Cellular uptake studies with 18 Ffluorodeoxyglucose (FDG), 177 Lu-DTPA-DG and 177 Lu-DTPA and a blocking study with 1.0 mg d-glucose were performed. Biodistribution, imaging, and radiotherapy studies of 177 Lu-DTPA-DG were performed with the SMMC-7721 model. Results: 177 Lu-DTPA-DG had a high radiochemical purity (>97%). The cellular uptake of 177 Lu-DTPA-DG was much higher than that of the 177 Lu-DTPA. The biodistribution of 177 Lu-DTPA-DG demonstrated that the complex accumulated in the tumor with high tumor/blood and tumor/muscle ratios. The tumors in mice in the 177 Lu-DTPA-DG group clearly displayed the high uptake of 177 Lu-DTPA-DG. After radiotherapy with 177 Lu-DTPA-DG, tumor growth decreased, and the overall survival was longer than that in the 177 LuCl 3 group (268.58-17.96 mm 3 vs. 507.43-55.72 mm 3 , p = 0.002) and the normal saline group (268.58-17.96 mm 3 vs. 483.68-27.51 mm 3 , p < 0.05). Conclusions: This preliminary study suggests that 177 Lu-DTPA-DG has the potential to become a liver radiopharmaceutical agent and should be further investigated.

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Investigation of receptor radionuclide therapy with 177Lu-DOTATATE in patients with GEP-NEN and a high Ki-67 proliferation index

Cited by 65 publications

References 27 publications

Evaluating the Role of Theranostics in Grade 3 Neuroendocrine Neoplasms

Evaluating the Role of Theranostics in Grade 3 Neuroendocrine Neoplasms

Theranostik von neuroendokrinen Tumoren

Preliminary Studies of ¹⁷⁷Lu-Diethylenetriamine Penta-Acetic Acid-Deoxyglucose in Hepatic Tumor-Bearing Mice

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Investigation of receptor radionuclide therapy with 177Lu-DOTATATE in patients with GEP-NEN and a high Ki-67 proliferation index

Cited by 65 publications

References 27 publications

Evaluating the Role of Theranostics in Grade 3 Neuroendocrine Neoplasms

Evaluating the Role of Theranostics in Grade 3 Neuroendocrine Neoplasms

Theranostik von neuroendokrinen Tumoren

Preliminary Studies of 177Lu-Diethylenetriamine Penta-Acetic Acid-Deoxyglucose in Hepatic Tumor-Bearing Mice

Contact Info

Product

Resources

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Preliminary Studies of ¹⁷⁷Lu-Diethylenetriamine Penta-Acetic Acid-Deoxyglucose in Hepatic Tumor-Bearing Mice