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Specific Uptake in the Bone Marrow Causes High Absorbed Red Marrow Doses During [(177)Lu]Lu-DOTATATE Treatment

Bone marrow suppression is a common side effect after [(177)Lu]Lu-DOTATATE treatment of neuroendocrine neoplasms. Neuroendocrine neoplasms share expression of somatostatin receptor type 2 with CD34-positive hematopoietic progenitor cells, potentially leading to active uptake in the radiosensitive re...

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Autores principales: Hemmingsson, Jens, Svensson, Johanna, Hallqvist, Andreas, Smits, Katja, Johanson, Viktor, Bernhardt, Peter
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Society of Nuclear Medicine 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10478826/
https://www.ncbi.nlm.nih.gov/pubmed/37290797
http://dx.doi.org/10.2967/jnumed.123.265484
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author Hemmingsson, Jens
Svensson, Johanna
Hallqvist, Andreas
Smits, Katja
Johanson, Viktor
Bernhardt, Peter
author_facet Hemmingsson, Jens
Svensson, Johanna
Hallqvist, Andreas
Smits, Katja
Johanson, Viktor
Bernhardt, Peter
author_sort Hemmingsson, Jens
collection PubMed
description Bone marrow suppression is a common side effect after [(177)Lu]Lu-DOTATATE treatment of neuroendocrine neoplasms. Neuroendocrine neoplasms share expression of somatostatin receptor type 2 with CD34-positive hematopoietic progenitor cells, potentially leading to active uptake in the radiosensitive red marrow region where these cells are located. This study aimed to identify and quantify specific red marrow uptake using SPECT/CT images collected after the first treatment cycle. Methods: Seventeen patients diagnosed with neuroendocrine neoplasms were treated with [(177)Lu]Lu-DOTATATE. Seven of them had confirmed bone metastases. After the first treatment cycle, each patient went through 4 SPECT/CT imaging sessions 4, 24, 48, and 168 h after administration. Monte Carlo–based reconstructions were used to quantify activity concentrations in tumors and multiple skeletal sites presumed to house red marrow: the T9–L5 vertebrae and the ilium portion of the hip bones. The activity concentration from the descending aorta was used as input in a compartment model intended to establish a pure red marrow biodistribution by separating the nonspecific blood-based contribution from the specific activity concentration in red marrow. The biodistributions from the compartment model were used to perform red marrow dosimetry at each skeletal site. Results: Increased uptake of [(177)Lu]Lu-DOTATATE was observed in the T9–L5 vertebrae and hip bones in all 17 patients compared with activity concentrations in the aorta. The mean specific red marrow uptake was 49% (range, 0%–93%) higher than the nonspecific uptake. The median (±SD) total absorbed dose to the red marrow was 0.056 ± 0.023 Gy/GBq and 0.043 ± 0.022 Gy/GBq for the mean of all vertebrae and hip bones, respectively. The patients with bone metastases had an absorbed dose of 0.085 ± 0.046 Gy/GBq and 0.069 ± 0.033 Gy/GBq for the vertebrae and hip bones, respectively. The red marrow elimination phase was statistically slower in patients with fast tumor elimination, which is in line with transferrin transport of (177)Lu back to the red marrow. Conclusion: Our results suggest that specific red marrow uptake of [(177)Lu]Lu-DOTATATE is in line with observations of somatostatin receptor type 2–expressing hematopoietic progenitor cells within the bone marrow. Blood-based dosimetry methods fail to account for the prolonged elimination of specific uptake and underestimate the absorbed dose to red marrow.
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spelling pubmed-104788262023-09-06 Specific Uptake in the Bone Marrow Causes High Absorbed Red Marrow Doses During [(177)Lu]Lu-DOTATATE Treatment Hemmingsson, Jens Svensson, Johanna Hallqvist, Andreas Smits, Katja Johanson, Viktor Bernhardt, Peter J Nucl Med Clinical Investigation Bone marrow suppression is a common side effect after [(177)Lu]Lu-DOTATATE treatment of neuroendocrine neoplasms. Neuroendocrine neoplasms share expression of somatostatin receptor type 2 with CD34-positive hematopoietic progenitor cells, potentially leading to active uptake in the radiosensitive red marrow region where these cells are located. This study aimed to identify and quantify specific red marrow uptake using SPECT/CT images collected after the first treatment cycle. Methods: Seventeen patients diagnosed with neuroendocrine neoplasms were treated with [(177)Lu]Lu-DOTATATE. Seven of them had confirmed bone metastases. After the first treatment cycle, each patient went through 4 SPECT/CT imaging sessions 4, 24, 48, and 168 h after administration. Monte Carlo–based reconstructions were used to quantify activity concentrations in tumors and multiple skeletal sites presumed to house red marrow: the T9–L5 vertebrae and the ilium portion of the hip bones. The activity concentration from the descending aorta was used as input in a compartment model intended to establish a pure red marrow biodistribution by separating the nonspecific blood-based contribution from the specific activity concentration in red marrow. The biodistributions from the compartment model were used to perform red marrow dosimetry at each skeletal site. Results: Increased uptake of [(177)Lu]Lu-DOTATATE was observed in the T9–L5 vertebrae and hip bones in all 17 patients compared with activity concentrations in the aorta. The mean specific red marrow uptake was 49% (range, 0%–93%) higher than the nonspecific uptake. The median (±SD) total absorbed dose to the red marrow was 0.056 ± 0.023 Gy/GBq and 0.043 ± 0.022 Gy/GBq for the mean of all vertebrae and hip bones, respectively. The patients with bone metastases had an absorbed dose of 0.085 ± 0.046 Gy/GBq and 0.069 ± 0.033 Gy/GBq for the vertebrae and hip bones, respectively. The red marrow elimination phase was statistically slower in patients with fast tumor elimination, which is in line with transferrin transport of (177)Lu back to the red marrow. Conclusion: Our results suggest that specific red marrow uptake of [(177)Lu]Lu-DOTATATE is in line with observations of somatostatin receptor type 2–expressing hematopoietic progenitor cells within the bone marrow. Blood-based dosimetry methods fail to account for the prolonged elimination of specific uptake and underestimate the absorbed dose to red marrow. Society of Nuclear Medicine 2023-09 /pmc/articles/PMC10478826/ /pubmed/37290797 http://dx.doi.org/10.2967/jnumed.123.265484 Text en © 2023 by the Society of Nuclear Medicine and Molecular Imaging. https://creativecommons.org/licenses/by/4.0/Immediate Open Access: Creative Commons Attribution 4.0 International License (CC BY) allows users to share and adapt with attribution, excluding materials credited to previous publications. License: https://creativecommons.org/licenses/by/4.0/. Details: http://jnm.snmjournals.org/site/misc/permission.xhtml.
spellingShingle Clinical Investigation
Hemmingsson, Jens
Svensson, Johanna
Hallqvist, Andreas
Smits, Katja
Johanson, Viktor
Bernhardt, Peter
Specific Uptake in the Bone Marrow Causes High Absorbed Red Marrow Doses During [(177)Lu]Lu-DOTATATE Treatment
title Specific Uptake in the Bone Marrow Causes High Absorbed Red Marrow Doses During [(177)Lu]Lu-DOTATATE Treatment
title_full Specific Uptake in the Bone Marrow Causes High Absorbed Red Marrow Doses During [(177)Lu]Lu-DOTATATE Treatment
title_fullStr Specific Uptake in the Bone Marrow Causes High Absorbed Red Marrow Doses During [(177)Lu]Lu-DOTATATE Treatment
title_full_unstemmed Specific Uptake in the Bone Marrow Causes High Absorbed Red Marrow Doses During [(177)Lu]Lu-DOTATATE Treatment
title_short Specific Uptake in the Bone Marrow Causes High Absorbed Red Marrow Doses During [(177)Lu]Lu-DOTATATE Treatment
title_sort specific uptake in the bone marrow causes high absorbed red marrow doses during [(177)lu]lu-dotatate treatment
topic Clinical Investigation
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10478826/
https://www.ncbi.nlm.nih.gov/pubmed/37290797
http://dx.doi.org/10.2967/jnumed.123.265484
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