Dosimetry of 64Cu-DOTA-AE105, a PET tracer for uPAR imaging

Morten Persson; Henrik H El Ali; Tina Binderup; Andreas Pfeifer; Jacob Madsen; Palle Rasmussen; Andreas Kjaer

doi:10.1016/j.nucmedbio.2013.12.007

Dosimetry of ⁶⁴Cu-DOTA-AE105, a PET tracer for uPAR imaging

Morten Persson, Henrik H El Ali, Tina Binderup, Andreas Pfeifer, Jacob Madsen, Palle Rasmussen, Andreas Kjaer

Endocrinology and Metabolism

13 Citations (Scopus)

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Abstract

⁶⁴Cu-DOTA-AE105 is a novel positron emission tomography (PET) tracer specific to the human urokinase-type plasminogen activator receptor (uPAR). In preparation of using this tracer in humans, as a new promising method to distinguish between indolent and aggressive cancers, we have performed PET studies in mice to evaluate the in vivo biodistribution and estimate human dosimetry of ⁶⁴Cu-DOTA-AE105. Methods: Five mice received iv tail injection of ⁶⁴Cu-DOTA-AE105 and were PET/CT scanned 1, 4.5 and 22h post injection. Volume-of-interest (VOI) were manually drawn on the following organs: heart, lung, liver, kidney, spleen, intestine, muscle, bone and bladder. The activity concentrations in the mentioned organs [%ID/g] were used for the dosimetry calculation. The %ID/g of each organ at 1, 4.5 and 22h was scaled to human value based on a difference between organ and body weights. The scaled values were then exported to OLINDA software for computation of the human absorbed doses. The residence times as well as effective dose equivalent for male and female could be obtained for each organ. To validate this approach, of human projection using mouse data, five mice received iv tail injection of another ⁶⁴Cu-DOTA peptide-based tracer, ⁶⁴Cu-DOTA-TATE, and underwent same procedure as just described. The human dosimetry estimates were then compared with observed human dosimetry estimate recently found in a first-in-man study using ⁶⁴Cu-DOTA-TATE. Results: Human estimates of ⁶⁴Cu-DOTA-AE105 revealed the heart wall to receive the highest dose (0.0918mSv/MBq) followed by the liver (0.0815mSv/MBq), All other organs/tissue were estimated to receive doses in the range of 0.02-0.04mSv/MBq. The mean effective whole-body dose of ⁶⁴Cu-DOTA-AE105 was estimated to be 0.0317mSv/MBq. Relatively good correlation between human predicted and observed dosimetry estimates for ⁶⁴Cu-DOTA-TATE was found. Importantly, the effective whole body dose was predicted with very high precision (predicted value: 0.0252mSv/Mbq, Observed value: 0.0315mSv/MBq) thus validating our approach for human dosimetry estimation. Conclusion: Favorable dosimetry estimates together with previously reported uPAR PET data fully support human testing of ⁶⁴Cu-DOTA-AE105.

Original language	English
Journal	Nuclear Medicine and Biology
Volume	41
Issue number	3
Pages (from-to)	290-5
Number of pages	6
ISSN	0969-8051
DOIs	https://doi.org/10.1016/j.nucmedbio.2013.12.007
Publication status	Published - Mar 2014

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@article{418a92c08fb4426b9d9266ef4b4758cb,

title = "Dosimetry of 64Cu-DOTA-AE105, a PET tracer for uPAR imaging",

abstract = "64Cu-DOTA-AE105 is a novel positron emission tomography (PET) tracer specific to the human urokinase-type plasminogen activator receptor (uPAR). In preparation of using this tracer in humans, as a new promising method to distinguish between indolent and aggressive cancers, we have performed PET studies in mice to evaluate the in vivo biodistribution and estimate human dosimetry of 64Cu-DOTA-AE105. Methods: Five mice received iv tail injection of 64Cu-DOTA-AE105 and were PET/CT scanned 1, 4.5 and 22h post injection. Volume-of-interest (VOI) were manually drawn on the following organs: heart, lung, liver, kidney, spleen, intestine, muscle, bone and bladder. The activity concentrations in the mentioned organs [%ID/g] were used for the dosimetry calculation. The %ID/g of each organ at 1, 4.5 and 22h was scaled to human value based on a difference between organ and body weights. The scaled values were then exported to OLINDA software for computation of the human absorbed doses. The residence times as well as effective dose equivalent for male and female could be obtained for each organ. To validate this approach, of human projection using mouse data, five mice received iv tail injection of another 64Cu-DOTA peptide-based tracer, 64Cu-DOTA-TATE, and underwent same procedure as just described. The human dosimetry estimates were then compared with observed human dosimetry estimate recently found in a first-in-man study using 64Cu-DOTA-TATE. Results: Human estimates of 64Cu-DOTA-AE105 revealed the heart wall to receive the highest dose (0.0918mSv/MBq) followed by the liver (0.0815mSv/MBq), All other organs/tissue were estimated to receive doses in the range of 0.02-0.04mSv/MBq. The mean effective whole-body dose of 64Cu-DOTA-AE105 was estimated to be 0.0317mSv/MBq. Relatively good correlation between human predicted and observed dosimetry estimates for 64Cu-DOTA-TATE was found. Importantly, the effective whole body dose was predicted with very high precision (predicted value: 0.0252mSv/Mbq, Observed value: 0.0315mSv/MBq) thus validating our approach for human dosimetry estimation. Conclusion: Favorable dosimetry estimates together with previously reported uPAR PET data fully support human testing of 64Cu-DOTA-AE105.",

keywords = "Animals, Copper Radioisotopes, Female, Humans, Male, Mice, Peptides, Positron-Emission Tomography, Radioactive Tracers, Radiometry, Receptors, Urokinase Plasminogen Activator",

author = "Morten Persson and {El Ali}, {Henrik H} and Tina Binderup and Andreas Pfeifer and Jacob Madsen and Palle Rasmussen and Andreas Kjaer",

year = "2014",

month = mar,

doi = "10.1016/j.nucmedbio.2013.12.007",

language = "English",

volume = "41",

pages = "290--5",

journal = "Nuclear Medicine and Biology",

issn = "0969-8051",

publisher = "Elsevier",

number = "3",

}

TY - JOUR

T1 - Dosimetry of 64Cu-DOTA-AE105, a PET tracer for uPAR imaging

AU - Persson, Morten

AU - El Ali, Henrik H

AU - Binderup, Tina

AU - Pfeifer, Andreas

AU - Madsen, Jacob

AU - Rasmussen, Palle

AU - Kjaer, Andreas

PY - 2014/3

Y1 - 2014/3

N2 - 64Cu-DOTA-AE105 is a novel positron emission tomography (PET) tracer specific to the human urokinase-type plasminogen activator receptor (uPAR). In preparation of using this tracer in humans, as a new promising method to distinguish between indolent and aggressive cancers, we have performed PET studies in mice to evaluate the in vivo biodistribution and estimate human dosimetry of 64Cu-DOTA-AE105. Methods: Five mice received iv tail injection of 64Cu-DOTA-AE105 and were PET/CT scanned 1, 4.5 and 22h post injection. Volume-of-interest (VOI) were manually drawn on the following organs: heart, lung, liver, kidney, spleen, intestine, muscle, bone and bladder. The activity concentrations in the mentioned organs [%ID/g] were used for the dosimetry calculation. The %ID/g of each organ at 1, 4.5 and 22h was scaled to human value based on a difference between organ and body weights. The scaled values were then exported to OLINDA software for computation of the human absorbed doses. The residence times as well as effective dose equivalent for male and female could be obtained for each organ. To validate this approach, of human projection using mouse data, five mice received iv tail injection of another 64Cu-DOTA peptide-based tracer, 64Cu-DOTA-TATE, and underwent same procedure as just described. The human dosimetry estimates were then compared with observed human dosimetry estimate recently found in a first-in-man study using 64Cu-DOTA-TATE. Results: Human estimates of 64Cu-DOTA-AE105 revealed the heart wall to receive the highest dose (0.0918mSv/MBq) followed by the liver (0.0815mSv/MBq), All other organs/tissue were estimated to receive doses in the range of 0.02-0.04mSv/MBq. The mean effective whole-body dose of 64Cu-DOTA-AE105 was estimated to be 0.0317mSv/MBq. Relatively good correlation between human predicted and observed dosimetry estimates for 64Cu-DOTA-TATE was found. Importantly, the effective whole body dose was predicted with very high precision (predicted value: 0.0252mSv/Mbq, Observed value: 0.0315mSv/MBq) thus validating our approach for human dosimetry estimation. Conclusion: Favorable dosimetry estimates together with previously reported uPAR PET data fully support human testing of 64Cu-DOTA-AE105.

AB - 64Cu-DOTA-AE105 is a novel positron emission tomography (PET) tracer specific to the human urokinase-type plasminogen activator receptor (uPAR). In preparation of using this tracer in humans, as a new promising method to distinguish between indolent and aggressive cancers, we have performed PET studies in mice to evaluate the in vivo biodistribution and estimate human dosimetry of 64Cu-DOTA-AE105. Methods: Five mice received iv tail injection of 64Cu-DOTA-AE105 and were PET/CT scanned 1, 4.5 and 22h post injection. Volume-of-interest (VOI) were manually drawn on the following organs: heart, lung, liver, kidney, spleen, intestine, muscle, bone and bladder. The activity concentrations in the mentioned organs [%ID/g] were used for the dosimetry calculation. The %ID/g of each organ at 1, 4.5 and 22h was scaled to human value based on a difference between organ and body weights. The scaled values were then exported to OLINDA software for computation of the human absorbed doses. The residence times as well as effective dose equivalent for male and female could be obtained for each organ. To validate this approach, of human projection using mouse data, five mice received iv tail injection of another 64Cu-DOTA peptide-based tracer, 64Cu-DOTA-TATE, and underwent same procedure as just described. The human dosimetry estimates were then compared with observed human dosimetry estimate recently found in a first-in-man study using 64Cu-DOTA-TATE. Results: Human estimates of 64Cu-DOTA-AE105 revealed the heart wall to receive the highest dose (0.0918mSv/MBq) followed by the liver (0.0815mSv/MBq), All other organs/tissue were estimated to receive doses in the range of 0.02-0.04mSv/MBq. The mean effective whole-body dose of 64Cu-DOTA-AE105 was estimated to be 0.0317mSv/MBq. Relatively good correlation between human predicted and observed dosimetry estimates for 64Cu-DOTA-TATE was found. Importantly, the effective whole body dose was predicted with very high precision (predicted value: 0.0252mSv/Mbq, Observed value: 0.0315mSv/MBq) thus validating our approach for human dosimetry estimation. Conclusion: Favorable dosimetry estimates together with previously reported uPAR PET data fully support human testing of 64Cu-DOTA-AE105.

KW - Animals

KW - Copper Radioisotopes

KW - Female

KW - Humans

KW - Male

KW - Mice

KW - Peptides

KW - Positron-Emission Tomography

KW - Radioactive Tracers

KW - Radiometry

KW - Receptors, Urokinase Plasminogen Activator

U2 - 10.1016/j.nucmedbio.2013.12.007

DO - 10.1016/j.nucmedbio.2013.12.007

M3 - Journal article

C2 - 24533988

SN - 0969-8051

VL - 41

SP - 290

EP - 295

JO - Nuclear Medicine and Biology

JF - Nuclear Medicine and Biology

IS - 3

ER -