Receptor depletion and recovery in small-intestinal neuroendocrine tumors and normal tissues after administration of a single intravenous dose of octreotide measured by 68Ga-DOTATOC PET/CT

Abstract Background Low-grade neuroendocrine tumors (NETs) are characterized by an abundance of somatostatin receptors (SSTR) that can be targeted with somatostatin analogs (SSA). When activated with a single dose of SSA, the receptor-ligand complex is internalized, and the receptor is by default re...

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Autores principales:	Ulrika Jahn, Ezgi Ilan, Irina Velikyan, Katarzyna Fröss-Baron, Mark Lubberink, Anders Sundin
Formato:	article
Lenguaje:	EN
Publicado:	SpringerOpen 2021
Materias:	68Ga-DOTATOC PET/CT Peptide Small-intestinal NET Receptor internalization SUV Medical physics. Medical radiology. Nuclear medicine R895-920
Acceso en línea:	https://doaj.org/article/f3e995fbfe0340859a0afc0a75e0b79b
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spelling	oai:doaj.org-article:f3e995fbfe0340859a0afc0a75e0b79b2021-11-28T12:15:11ZReceptor depletion and recovery in small-intestinal neuroendocrine tumors and normal tissues after administration of a single intravenous dose of octreotide measured by 68Ga-DOTATOC PET/CT10.1186/s13550-021-00860-02191-219Xhttps://doaj.org/article/f3e995fbfe0340859a0afc0a75e0b79b2021-11-01T00:00:00Zhttps://doi.org/10.1186/s13550-021-00860-0https://doaj.org/toc/2191-219XAbstract Background Low-grade neuroendocrine tumors (NETs) are characterized by an abundance of somatostatin receptors (SSTR) that can be targeted with somatostatin analogs (SSA). When activated with a single dose of SSA, the receptor-ligand complex is internalized, and the receptor is by default recycled within 24 h. Ongoing medication with long-acting SSAs at 68Ga-DOTA-SSA-PET has been shown to increase the tumor-to-normal organ contrast. This study was performed to investigate the time-dependent extended effect (7 h) of a single intravenous dose of 400 µg short-acting octreotide on the tumor versus normal tissue uptake of 68Ga-DOTATOC. Methods Patients with small-intestinal NETs received a single intravenous dose of 400 µg octreotide and underwent dynamic abdominal 68Ga-DOTATOC-PET/CT at three sessions (0, 3 and 6 h) plus static whole-body (WB) PET/CT (1, 4 and 7 h), starting each PET/CT session by administering 167 ± 21 MBq, 23.5 ± 4.2 µg (mean ± SD, n = 12) of 68Ga-DOTATOC. A previously acquired clinical whole-body 68Ga-DOTATOC scan was used as baseline. SUV and net uptake rate Ki were calculated in tumors, and SUV in healthy organs. Results Tumor SUV decreased significantly from baseline to 1 h post-injection but subsequently increased over time and became similar to baseline at 4 h and 7 h. The tumor net uptake rate, Ki, similarly increased significantly over time and showed a linear correlation both with SUV and tumor-to-blood ratio. By contrast, the uptake in liver, spleen and pancreas remained significantly below baseline levels also at 7 h and the receptor turn-over in tumors thus exceeded that in the normal tissue, with restitution of tumor 68Ga-DOTATOC uptake mainly completed at 7 h. These results however differed depending on tumor size, with significant increases in Ki and SUV between the 1st and 2nd PET, in large tumors (≥ 4 mL) but not in small (> 1 to < 4 mL) tumors. Conclusion SSTR recycling is faster in small-intestinal NETs than in liver, spleen and pancreas. This opens the possibility to protect normal tissues during PRRT by administering a single dose of cold peptide hours before peptide receptor radionuclide therapy (PRRT), and most likely additionally improve the availability and uptake of the therapeutic preparation in the tumors.Ulrika JahnEzgi IlanIrina VelikyanKatarzyna Fröss-BaronMark LubberinkAnders SundinSpringerOpenarticle68Ga-DOTATOCPET/CTPeptideSmall-intestinal NETReceptor internalizationSUVMedical physics. Medical radiology. Nuclear medicineR895-920ENEJNMMI Research, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	68Ga-DOTATOC PET/CT Peptide Small-intestinal NET Receptor internalization SUV Medical physics. Medical radiology. Nuclear medicine R895-920
spellingShingle	68Ga-DOTATOC PET/CT Peptide Small-intestinal NET Receptor internalization SUV Medical physics. Medical radiology. Nuclear medicine R895-920 Ulrika Jahn Ezgi Ilan Irina Velikyan Katarzyna Fröss-Baron Mark Lubberink Anders Sundin Receptor depletion and recovery in small-intestinal neuroendocrine tumors and normal tissues after administration of a single intravenous dose of octreotide measured by 68Ga-DOTATOC PET/CT
description	Abstract Background Low-grade neuroendocrine tumors (NETs) are characterized by an abundance of somatostatin receptors (SSTR) that can be targeted with somatostatin analogs (SSA). When activated with a single dose of SSA, the receptor-ligand complex is internalized, and the receptor is by default recycled within 24 h. Ongoing medication with long-acting SSAs at 68Ga-DOTA-SSA-PET has been shown to increase the tumor-to-normal organ contrast. This study was performed to investigate the time-dependent extended effect (7 h) of a single intravenous dose of 400 µg short-acting octreotide on the tumor versus normal tissue uptake of 68Ga-DOTATOC. Methods Patients with small-intestinal NETs received a single intravenous dose of 400 µg octreotide and underwent dynamic abdominal 68Ga-DOTATOC-PET/CT at three sessions (0, 3 and 6 h) plus static whole-body (WB) PET/CT (1, 4 and 7 h), starting each PET/CT session by administering 167 ± 21 MBq, 23.5 ± 4.2 µg (mean ± SD, n = 12) of 68Ga-DOTATOC. A previously acquired clinical whole-body 68Ga-DOTATOC scan was used as baseline. SUV and net uptake rate Ki were calculated in tumors, and SUV in healthy organs. Results Tumor SUV decreased significantly from baseline to 1 h post-injection but subsequently increased over time and became similar to baseline at 4 h and 7 h. The tumor net uptake rate, Ki, similarly increased significantly over time and showed a linear correlation both with SUV and tumor-to-blood ratio. By contrast, the uptake in liver, spleen and pancreas remained significantly below baseline levels also at 7 h and the receptor turn-over in tumors thus exceeded that in the normal tissue, with restitution of tumor 68Ga-DOTATOC uptake mainly completed at 7 h. These results however differed depending on tumor size, with significant increases in Ki and SUV between the 1st and 2nd PET, in large tumors (≥ 4 mL) but not in small (> 1 to < 4 mL) tumors. Conclusion SSTR recycling is faster in small-intestinal NETs than in liver, spleen and pancreas. This opens the possibility to protect normal tissues during PRRT by administering a single dose of cold peptide hours before peptide receptor radionuclide therapy (PRRT), and most likely additionally improve the availability and uptake of the therapeutic preparation in the tumors.
format	article
author	Ulrika Jahn Ezgi Ilan Irina Velikyan Katarzyna Fröss-Baron Mark Lubberink Anders Sundin
author_facet	Ulrika Jahn Ezgi Ilan Irina Velikyan Katarzyna Fröss-Baron Mark Lubberink Anders Sundin
author_sort	Ulrika Jahn
title	Receptor depletion and recovery in small-intestinal neuroendocrine tumors and normal tissues after administration of a single intravenous dose of octreotide measured by 68Ga-DOTATOC PET/CT
title_short	Receptor depletion and recovery in small-intestinal neuroendocrine tumors and normal tissues after administration of a single intravenous dose of octreotide measured by 68Ga-DOTATOC PET/CT
title_full	Receptor depletion and recovery in small-intestinal neuroendocrine tumors and normal tissues after administration of a single intravenous dose of octreotide measured by 68Ga-DOTATOC PET/CT
title_fullStr	Receptor depletion and recovery in small-intestinal neuroendocrine tumors and normal tissues after administration of a single intravenous dose of octreotide measured by 68Ga-DOTATOC PET/CT
title_full_unstemmed	Receptor depletion and recovery in small-intestinal neuroendocrine tumors and normal tissues after administration of a single intravenous dose of octreotide measured by 68Ga-DOTATOC PET/CT
title_sort	receptor depletion and recovery in small-intestinal neuroendocrine tumors and normal tissues after administration of a single intravenous dose of octreotide measured by 68ga-dotatoc pet/ct
publisher	SpringerOpen
publishDate	2021
url	https://doaj.org/article/f3e995fbfe0340859a0afc0a75e0b79b
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Receptor depletion and recovery in small-intestinal neuroendocrine tumors and normal tissues after administration of a single intravenous dose of octreotide measured by 68Ga-DOTATOC PET/CT

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