Neodymium-140 DOTA-LM3: Evaluation of an In Vivo Generator for PET with a Non-Internalizing Vector

Research output: Contribution to journalJournal article – Annual report year: 2017Researchpeer-review

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Neodymium-140 DOTA-LM3 : Evaluation of an In Vivo Generator for PET with a Non-Internalizing Vector. / Severin, Gregory; Kristensen, Lotte K.; Nielsen, Carsten H.; Fonslet, Jesper; Jensen, Andreas Tue Ingemann; Frellsen, Anders Floor; Jensen, K. M.; Elema, Dennis Ringkjøbing; Maecke, Helmut; Kjær, Andreas ; Johnston, Karl; Köster, Ulli.

In: Frontiers in Medicine, Vol. 4, 98, 2017.

Research output: Contribution to journalJournal article – Annual report year: 2017Researchpeer-review

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@article{2f83b663615b484eb3756c16ccdf8786,
title = "Neodymium-140 DOTA-LM3: Evaluation of an In Vivo Generator for PET with a Non-Internalizing Vector",
abstract = "140Nd (t1/2 = 3.4 days), owing to its short-lived positron emitting daughter 140Pr (t1/2 = 3.4 min), has promise as an in vivo generator for positron emission tomography (PET). However, the electron capture decay of 140Nd is chemically disruptive to macrocycle-based radiolabeling, meaning that an in vivo redistribution of the daughter 140Pr is expected before positron emission. The purpose of this study was to determine how the delayed positron from the de-labeled 140Pr affects preclinical imaging with 140Nd. To explore the effect, 140Nd was produced at CERN-ISOLDE, reacted with the somatostatin analogue, DOTA-LM3 (1,4,7,10- tetraazacyclododecane, 1,4,7- tri acetic acid, 10- acetamide N - p-Cl-Phecyclo(D-Cys-Tyr-d-4-amino-Phe(carbamoyl)-Lys-Thr-Cys)D-Tyr-NH2) and injected into H727 xenograft bearing mice. Comparative pre- and post-mortem PET imaging at 16 h postinjection was used to quantify the in vivo redistribution of 140Pr following 140Nd decay. The somatostatin receptor-positive pancreas exhibited the highest tissue accumulation of 140Nd-DOTA-LM3 (13{\%} ID/g at 16 h) coupled with the largest observed redistribution rate, where 56 ± 7{\%} (n = 4, mean ± SD) of the in situ produced 140Pr washed out of the pancreas before decay. Contrastingly, the liver, spleen, and lungs acted as strong sink organs for free 140Pr3+. Based upon these results, we conclude that 140Nd imaging with a non-internalizing vector convolutes the biodistribution of the tracer with the accumulation pattern of free 140Pr. This redistribution phenomenon may show promise as a probe of the cellular interaction with the vector, such as in determining tissue dependent internalization behavior.",
keywords = "140Nd, 140Pr, DOTA-LM3, in vivo generator, Internalization, Positron emission tomography",
author = "Gregory Severin and Kristensen, {Lotte K.} and Nielsen, {Carsten H.} and Jesper Fonslet and Jensen, {Andreas Tue Ingemann} and Frellsen, {Anders Floor} and Jensen, {K. M.} and Elema, {Dennis Ringkj{\o}bing} and Helmut Maecke and Andreas Kj{\ae}r and Karl Johnston and Ulli K{\"o}ster",
year = "2017",
doi = "10.3389/fmed.2017.00098",
language = "English",
volume = "4",
journal = "Frontiers in Medicine",
issn = "2296-858X",
publisher = "Frontiers Media S.A.",

}

RIS

TY - JOUR

T1 - Neodymium-140 DOTA-LM3

T2 - Evaluation of an In Vivo Generator for PET with a Non-Internalizing Vector

AU - Severin, Gregory

AU - Kristensen, Lotte K.

AU - Nielsen, Carsten H.

AU - Fonslet, Jesper

AU - Jensen, Andreas Tue Ingemann

AU - Frellsen, Anders Floor

AU - Jensen, K. M.

AU - Elema, Dennis Ringkjøbing

AU - Maecke, Helmut

AU - Kjær, Andreas

AU - Johnston, Karl

AU - Köster, Ulli

PY - 2017

Y1 - 2017

N2 - 140Nd (t1/2 = 3.4 days), owing to its short-lived positron emitting daughter 140Pr (t1/2 = 3.4 min), has promise as an in vivo generator for positron emission tomography (PET). However, the electron capture decay of 140Nd is chemically disruptive to macrocycle-based radiolabeling, meaning that an in vivo redistribution of the daughter 140Pr is expected before positron emission. The purpose of this study was to determine how the delayed positron from the de-labeled 140Pr affects preclinical imaging with 140Nd. To explore the effect, 140Nd was produced at CERN-ISOLDE, reacted with the somatostatin analogue, DOTA-LM3 (1,4,7,10- tetraazacyclododecane, 1,4,7- tri acetic acid, 10- acetamide N - p-Cl-Phecyclo(D-Cys-Tyr-d-4-amino-Phe(carbamoyl)-Lys-Thr-Cys)D-Tyr-NH2) and injected into H727 xenograft bearing mice. Comparative pre- and post-mortem PET imaging at 16 h postinjection was used to quantify the in vivo redistribution of 140Pr following 140Nd decay. The somatostatin receptor-positive pancreas exhibited the highest tissue accumulation of 140Nd-DOTA-LM3 (13% ID/g at 16 h) coupled with the largest observed redistribution rate, where 56 ± 7% (n = 4, mean ± SD) of the in situ produced 140Pr washed out of the pancreas before decay. Contrastingly, the liver, spleen, and lungs acted as strong sink organs for free 140Pr3+. Based upon these results, we conclude that 140Nd imaging with a non-internalizing vector convolutes the biodistribution of the tracer with the accumulation pattern of free 140Pr. This redistribution phenomenon may show promise as a probe of the cellular interaction with the vector, such as in determining tissue dependent internalization behavior.

AB - 140Nd (t1/2 = 3.4 days), owing to its short-lived positron emitting daughter 140Pr (t1/2 = 3.4 min), has promise as an in vivo generator for positron emission tomography (PET). However, the electron capture decay of 140Nd is chemically disruptive to macrocycle-based radiolabeling, meaning that an in vivo redistribution of the daughter 140Pr is expected before positron emission. The purpose of this study was to determine how the delayed positron from the de-labeled 140Pr affects preclinical imaging with 140Nd. To explore the effect, 140Nd was produced at CERN-ISOLDE, reacted with the somatostatin analogue, DOTA-LM3 (1,4,7,10- tetraazacyclododecane, 1,4,7- tri acetic acid, 10- acetamide N - p-Cl-Phecyclo(D-Cys-Tyr-d-4-amino-Phe(carbamoyl)-Lys-Thr-Cys)D-Tyr-NH2) and injected into H727 xenograft bearing mice. Comparative pre- and post-mortem PET imaging at 16 h postinjection was used to quantify the in vivo redistribution of 140Pr following 140Nd decay. The somatostatin receptor-positive pancreas exhibited the highest tissue accumulation of 140Nd-DOTA-LM3 (13% ID/g at 16 h) coupled with the largest observed redistribution rate, where 56 ± 7% (n = 4, mean ± SD) of the in situ produced 140Pr washed out of the pancreas before decay. Contrastingly, the liver, spleen, and lungs acted as strong sink organs for free 140Pr3+. Based upon these results, we conclude that 140Nd imaging with a non-internalizing vector convolutes the biodistribution of the tracer with the accumulation pattern of free 140Pr. This redistribution phenomenon may show promise as a probe of the cellular interaction with the vector, such as in determining tissue dependent internalization behavior.

KW - 140Nd

KW - 140Pr

KW - DOTA-LM3

KW - in vivo generator

KW - Internalization

KW - Positron emission tomography

U2 - 10.3389/fmed.2017.00098

DO - 10.3389/fmed.2017.00098

M3 - Journal article

VL - 4

JO - Frontiers in Medicine

JF - Frontiers in Medicine

SN - 2296-858X

M1 - 98

ER -