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Does PRRT with standard activities of (177)Lu-octreotate really achieve relevant somatostatin receptor saturation in target tumor lesions?: insights from intra-therapeutic receptor imaging in patients with metastatic gastroenteropancreatic neuroendocrine tumors

BACKGROUND: Peptide receptor radionuclide therapy (PRRT) with (177)Lu-[DOTA(0),Tyr(3)]octreotate ((177)Lu-octreotate) is generally performed using a fixed activity of 7.4 GBq (200 mCi) per course bound to 180 to 300 μg of the peptide. While this single activity may lead to suboptimal radiation doses...

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Autores principales: Sabet, Amir, Nagarajah, James, Dogan, Ahmet Semih, Biersack, Hans-Jürgen, Sabet, Amin, Guhlke, Stefan, Ezziddin, Samer
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3877953/
https://www.ncbi.nlm.nih.gov/pubmed/24369053
http://dx.doi.org/10.1186/2191-219X-3-82
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author Sabet, Amir
Nagarajah, James
Dogan, Ahmet Semih
Biersack, Hans-Jürgen
Sabet, Amin
Guhlke, Stefan
Ezziddin, Samer
author_facet Sabet, Amir
Nagarajah, James
Dogan, Ahmet Semih
Biersack, Hans-Jürgen
Sabet, Amin
Guhlke, Stefan
Ezziddin, Samer
author_sort Sabet, Amir
collection PubMed
description BACKGROUND: Peptide receptor radionuclide therapy (PRRT) with (177)Lu-[DOTA(0),Tyr(3)]octreotate ((177)Lu-octreotate) is generally performed using a fixed activity of 7.4 GBq (200 mCi) per course bound to 180 to 300 μg of the peptide. While this single activity may lead to suboptimal radiation doses in neuroendocrine tumors (NET) with advanced or bulky disease, dose escalation has been withheld due to concerns on potential tumor somatostatin receptor saturation with reduced efficacy of the added activity. In vivo saturation effects during standard-dose PRRT based on quantification of pre- and intra-therapeutic (68)Ga-DOTATOC positron emission tomography (PET) imaging might guide potential dose escalation. METHODS: Five patients with metastatic NET of the pancreas underwent (68)Ga-DOTATOC PET/CT before and directly after standard-dose PRRT with (177)Lu-octreotate. In each patient, four target tumor lesions, normal liver parenchyma, and the spleen were evaluated and the ratios of SUV(max) of the target lesions to liver (SUV(T/L)) and spleen (SUV(T/S)) were calculated; paired Student's t test was performed with p < 0.05 for pre-/intra-PRRT comparisons. RESULTS: The mean intra-therapeutic tumor SUV(max) showed no significant change (per-lesion paired t test) compared to pretreatment values (-9.1%, p = 0.226). In contrast, the SUV(max) of the normal liver parenchyma and spleen were significantly lower directly after infusion of 7.4 GBq (177)Lu-octreotate. Consequently, SUV(T/L) and SUV(T/S) increased significantly from pretreatment to intra-therapeutic examination: SUV(T/L) (p < 0.001) from 2.8 ± 1.3 (1.3 to 5.8) to 4.7 ± 3.0 (2.1 to 12.7) and SUV(T/S) (p < 0.001) from 1.2 ± 0.7 (0.4 to 3.0) to 3.5 ± 1.5 (1.6 to 7.9). CONCLUSIONS: This small retrospective study provides preliminary evidence for the absence of relevant in vivo saturation of somatostatin receptor subtype 2 (sst2) in tumor lesions during PRRT with standard activities of (177)Lu-octreotate in contrast to normal tissue (liver, spleen) showing limited receptor capacity. After being confirmed by larger series, this observation will have significant implications for PRRT: (1) Higher activities of (177)Lu-octreotate might be considered feasible in patients with high tumor disease burden or clinical need for remission, and (2) striving to reduce the amount of peptide used in standard preparations of (177)Lu-octreotate appears futile.
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spelling pubmed-38779532014-01-03 Does PRRT with standard activities of (177)Lu-octreotate really achieve relevant somatostatin receptor saturation in target tumor lesions?: insights from intra-therapeutic receptor imaging in patients with metastatic gastroenteropancreatic neuroendocrine tumors Sabet, Amir Nagarajah, James Dogan, Ahmet Semih Biersack, Hans-Jürgen Sabet, Amin Guhlke, Stefan Ezziddin, Samer EJNMMI Res Original Research BACKGROUND: Peptide receptor radionuclide therapy (PRRT) with (177)Lu-[DOTA(0),Tyr(3)]octreotate ((177)Lu-octreotate) is generally performed using a fixed activity of 7.4 GBq (200 mCi) per course bound to 180 to 300 μg of the peptide. While this single activity may lead to suboptimal radiation doses in neuroendocrine tumors (NET) with advanced or bulky disease, dose escalation has been withheld due to concerns on potential tumor somatostatin receptor saturation with reduced efficacy of the added activity. In vivo saturation effects during standard-dose PRRT based on quantification of pre- and intra-therapeutic (68)Ga-DOTATOC positron emission tomography (PET) imaging might guide potential dose escalation. METHODS: Five patients with metastatic NET of the pancreas underwent (68)Ga-DOTATOC PET/CT before and directly after standard-dose PRRT with (177)Lu-octreotate. In each patient, four target tumor lesions, normal liver parenchyma, and the spleen were evaluated and the ratios of SUV(max) of the target lesions to liver (SUV(T/L)) and spleen (SUV(T/S)) were calculated; paired Student's t test was performed with p < 0.05 for pre-/intra-PRRT comparisons. RESULTS: The mean intra-therapeutic tumor SUV(max) showed no significant change (per-lesion paired t test) compared to pretreatment values (-9.1%, p = 0.226). In contrast, the SUV(max) of the normal liver parenchyma and spleen were significantly lower directly after infusion of 7.4 GBq (177)Lu-octreotate. Consequently, SUV(T/L) and SUV(T/S) increased significantly from pretreatment to intra-therapeutic examination: SUV(T/L) (p < 0.001) from 2.8 ± 1.3 (1.3 to 5.8) to 4.7 ± 3.0 (2.1 to 12.7) and SUV(T/S) (p < 0.001) from 1.2 ± 0.7 (0.4 to 3.0) to 3.5 ± 1.5 (1.6 to 7.9). CONCLUSIONS: This small retrospective study provides preliminary evidence for the absence of relevant in vivo saturation of somatostatin receptor subtype 2 (sst2) in tumor lesions during PRRT with standard activities of (177)Lu-octreotate in contrast to normal tissue (liver, spleen) showing limited receptor capacity. After being confirmed by larger series, this observation will have significant implications for PRRT: (1) Higher activities of (177)Lu-octreotate might be considered feasible in patients with high tumor disease burden or clinical need for remission, and (2) striving to reduce the amount of peptide used in standard preparations of (177)Lu-octreotate appears futile. Springer 2013-12-26 /pmc/articles/PMC3877953/ /pubmed/24369053 http://dx.doi.org/10.1186/2191-219X-3-82 Text en Copyright © 2013 Sabet et al.; licensee Springer. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Research
Sabet, Amir
Nagarajah, James
Dogan, Ahmet Semih
Biersack, Hans-Jürgen
Sabet, Amin
Guhlke, Stefan
Ezziddin, Samer
Does PRRT with standard activities of (177)Lu-octreotate really achieve relevant somatostatin receptor saturation in target tumor lesions?: insights from intra-therapeutic receptor imaging in patients with metastatic gastroenteropancreatic neuroendocrine tumors
title Does PRRT with standard activities of (177)Lu-octreotate really achieve relevant somatostatin receptor saturation in target tumor lesions?: insights from intra-therapeutic receptor imaging in patients with metastatic gastroenteropancreatic neuroendocrine tumors
title_full Does PRRT with standard activities of (177)Lu-octreotate really achieve relevant somatostatin receptor saturation in target tumor lesions?: insights from intra-therapeutic receptor imaging in patients with metastatic gastroenteropancreatic neuroendocrine tumors
title_fullStr Does PRRT with standard activities of (177)Lu-octreotate really achieve relevant somatostatin receptor saturation in target tumor lesions?: insights from intra-therapeutic receptor imaging in patients with metastatic gastroenteropancreatic neuroendocrine tumors
title_full_unstemmed Does PRRT with standard activities of (177)Lu-octreotate really achieve relevant somatostatin receptor saturation in target tumor lesions?: insights from intra-therapeutic receptor imaging in patients with metastatic gastroenteropancreatic neuroendocrine tumors
title_short Does PRRT with standard activities of (177)Lu-octreotate really achieve relevant somatostatin receptor saturation in target tumor lesions?: insights from intra-therapeutic receptor imaging in patients with metastatic gastroenteropancreatic neuroendocrine tumors
title_sort does prrt with standard activities of (177)lu-octreotate really achieve relevant somatostatin receptor saturation in target tumor lesions?: insights from intra-therapeutic receptor imaging in patients with metastatic gastroenteropancreatic neuroendocrine tumors
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3877953/
https://www.ncbi.nlm.nih.gov/pubmed/24369053
http://dx.doi.org/10.1186/2191-219X-3-82
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