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Non-invasive imaging methodologies for assessment of radiation damage to bone marrow and kidneys from peptide receptor radionuclide therapy. : -

Ahlstedt, Jonas LU ; Johansson, Edvin ; Sydoff, Marie LU ; Karlsson, Helena ; Thordarson, Eddie LU ; Gram, Magnus LU orcid and Eriksson, Olof (2019) In Neuroendocrinology 110(1-2). p.130-138
Abstract
Background/Aims: Peptide receptor radionuclide therapy (PRRT) is becoming clinical routine for management of neuroendocrine tumours. The number of PRRT cycles is correlated with treatment effect but theoretically limited by off-target radiation damage to kidneys and bone marrow. New imaging biomarkers for assessment of PRRT tissue damage would enable evaluation of novel renal and bone marrow protective agents, as well as personalised PRRT treatment regiments. Methods: Mice treated with [177Lu]Lu-DOTA-TATE PRRT or vehicle were examined at baseline and following treatment with [18F]fluorothymidine (FLT) positron emission tomography (PET) and technetium-99m-mercapto-acetyl-tri-glycine ([99mTc]Tc-Mag3) single-photon emission tomography (SPECT)... (More)
Background/Aims: Peptide receptor radionuclide therapy (PRRT) is becoming clinical routine for management of neuroendocrine tumours. The number of PRRT cycles is correlated with treatment effect but theoretically limited by off-target radiation damage to kidneys and bone marrow. New imaging biomarkers for assessment of PRRT tissue damage would enable evaluation of novel renal and bone marrow protective agents, as well as personalised PRRT treatment regiments. Methods: Mice treated with [177Lu]Lu-DOTA-TATE PRRT or vehicle were examined at baseline and following treatment with [18F]fluorothymidine (FLT) positron emission tomography (PET) and technetium-99m-mercapto-acetyl-tri-glycine ([99mTc]Tc-Mag3) single-photon emission tomography (SPECT) to assess dynamic changes in bone marrow proliferation and renal function, respectively. Results: Bone marrow proliferation as assessed by [18F]FLT was decreased 2 days after PRRT treatment, but not vehicle, compared to baseline (target-to-background ratio [TBRmax] baseline:1.69 ± 0.29 vs. TBRmax PRRT: 0.91 ± 0.02, p < 0.01). Renal function as assessed by [99mTc]Tc-Mag3 SPECT was similarly decreased 2 days following PRRT compared to vehicle (fractional uptake rate [FUR] vehicle: 0.030 ± 0.014 s–1 vs. FUR PRRT: 0.0051 ± 0.0028 s–1, p < 0.01). Conclusion: [18F]FLT PET and [99mTc]Tc-Mag3 SPECT are promising techniques for assessing bone marrow and renal injury from [177Lu]Lu-DOTA-TATE PRRT and may potentially improve patient management by allowing evaluation of protective interventions as well as enabling personalised PRRT treatments. (Less)
Abstract (Swedish)
Background/Aims: Peptide receptor radionuclide therapy (PRRT) is becoming clinical routine for management of Neuroendocrine Tumours. The number of PRRT cycles are correlated with treatment effect but theoretically limited by off-target radiation damage to kidneys and bone marrow. New imaging biomarkers for assessment of PRRT tissue damage would enable evaluation of novel renal and bone marrow protective agents, as well as personalized PRRT treatment regiments.
METHODS:
Mice treated with [177Lu]Lu-DOTA-TATE PRRT or vehicle were examined at baseline and following treatment with [18F]FLT PET and [99mTc]Tc-Mag3 SPECT to assess dynamic changes in bone marrow proliferation and renal function, respectively.
RESULTS:
Bone marrow... (More)
Background/Aims: Peptide receptor radionuclide therapy (PRRT) is becoming clinical routine for management of Neuroendocrine Tumours. The number of PRRT cycles are correlated with treatment effect but theoretically limited by off-target radiation damage to kidneys and bone marrow. New imaging biomarkers for assessment of PRRT tissue damage would enable evaluation of novel renal and bone marrow protective agents, as well as personalized PRRT treatment regiments.
METHODS:
Mice treated with [177Lu]Lu-DOTA-TATE PRRT or vehicle were examined at baseline and following treatment with [18F]FLT PET and [99mTc]Tc-Mag3 SPECT to assess dynamic changes in bone marrow proliferation and renal function, respectively.
RESULTS:
Bone marrow proliferation as assessed by [18F]FLT was decreased two days after PRRT treatment, but not vehicle, compared to baseline (Target-to-Background ratio (TBRmax) baseline:1.69±0.29 vs TBRmax PRRT: 0.91±0.02, p<0.01). Renal function as assessed by [99mTc]Tc-Mag3 SPECT was similarly decreased two days following PRRT compared to vehicle (Fractional Uptake Rate (FUR) vehicle: 0.030±0.014 s-1 vs FUR PRRT: 0.0051±0.0028 s-1, p<0.01).
CONCLUSION:
[18F]FLT PET and [99mTc]Tc-Mag3 SPECT are promising techniques for assessing bone marrow and renal injury from [177Lu]Lu-DOTA-TATE PRRT, and may potentially improve patient management by allowing evaluation of protective interventions as well as enabling personalized PRRT treatments. (Less)
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author
; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Peptide receptor radionuclide therapy · Radiation damage · Positron emission tomography · Single-photon emission tomography · Renal protection
in
Neuroendocrinology
volume
110
issue
1-2
pages
130 - 138
publisher
Karger
external identifiers
  • scopus:85077728392
  • pmid:30999299
ISSN
1423-0194
DOI
10.1159/000500473
language
English
LU publication?
yes
id
953161cf-147b-4d36-b013-fbfdf2b628e2
date added to LUP
2019-11-07 14:02:09
date last changed
2022-04-18 18:51:10
@article{953161cf-147b-4d36-b013-fbfdf2b628e2,
  abstract     = {{Background/Aims: Peptide receptor radionuclide therapy (PRRT) is becoming clinical routine for management of neuroendocrine tumours. The number of PRRT cycles is correlated with treatment effect but theoretically limited by off-target radiation damage to kidneys and bone marrow. New imaging biomarkers for assessment of PRRT tissue damage would enable evaluation of novel renal and bone marrow protective agents, as well as personalised PRRT treatment regiments. Methods: Mice treated with [177Lu]Lu-DOTA-TATE PRRT or vehicle were examined at baseline and following treatment with [18F]fluorothymidine (FLT) positron emission tomography (PET) and technetium-99m-mercapto-acetyl-tri-glycine ([99mTc]Tc-Mag3) single-photon emission tomography (SPECT) to assess dynamic changes in bone marrow proliferation and renal function, respectively. Results: Bone marrow proliferation as assessed by [18F]FLT was decreased 2 days after PRRT treatment, but not vehicle, compared to baseline (target-to-background ratio [TBRmax] baseline:1.69 ± 0.29 vs. TBRmax PRRT: 0.91 ± 0.02, p &lt; 0.01). Renal function as assessed by [99mTc]Tc-Mag3 SPECT was similarly decreased 2 days following PRRT compared to vehicle (fractional uptake rate [FUR] vehicle: 0.030 ± 0.014 s–1 vs. FUR PRRT: 0.0051 ± 0.0028 s–1, p &lt; 0.01). Conclusion: [18F]FLT PET and [99mTc]Tc-Mag3 SPECT are promising techniques for assessing bone marrow and renal injury from [177Lu]Lu-DOTA-TATE PRRT and may potentially improve patient management by allowing evaluation of protective interventions as well as enabling personalised PRRT treatments.}},
  author       = {{Ahlstedt, Jonas and Johansson, Edvin and Sydoff, Marie and Karlsson, Helena and Thordarson, Eddie and Gram, Magnus and Eriksson, Olof}},
  issn         = {{1423-0194}},
  keywords     = {{Peptide receptor radionuclide therapy · Radiation damage · Positron emission tomography · Single-photon emission tomography · Renal protection}},
  language     = {{eng}},
  month        = {{04}},
  number       = {{1-2}},
  pages        = {{130--138}},
  publisher    = {{Karger}},
  series       = {{Neuroendocrinology}},
  title        = {{Non-invasive imaging methodologies for assessment of radiation damage to bone marrow and kidneys from peptide receptor radionuclide therapy. : -}},
  url          = {{http://dx.doi.org/10.1159/000500473}},
  doi          = {{10.1159/000500473}},
  volume       = {{110}},
  year         = {{2019}},
}