PET in vivo generators 134Ce and 140Nd on an internalizing monoclonal antibody probe

G. W. Severin; J. Fonslet; L. K. Kristensen; C. H. Nielsen; A. I. Jensen; A. Kjær; A. P. Mazar; K. Johnston; U. Köster

doi:10.1038/s41598-022-07147-x

PET in vivo generators¹³⁴Ce and ¹⁴⁰Nd on an internalizing monoclonal antibody probe

G. W. Severin^*, J. Fonslet, L. K. Kristensen, C. H. Nielsen, A. I. Jensen, A. Kjær, A. P. Mazar, K. Johnston, U. Köster

^*Corresponding author for this work

Department of Health Technology

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Abstract

The in vivo-generator radionuclides ¹⁴⁰Nd (t_1/2 = 3.4 d) and ¹³⁴Ce (t_1/2 = 3.2 d) were used to trace a urokinase-type plasminogen activator (uPA)-targeting mouse monoclonal antibody, ATN-291, in U87 MG xenograft tumor-bearing mice. ATN-291 is known to internalize on the uPA/uPA-receptor pair, making it an appropriate targeting vector for investigating the fate of in vivo generator daughters on internalizing probes. Ante-mortem and post-mortem PET imaging at 120 h post-injection gave no indication of redistribution of the positron emitting daughter nuclides ¹³⁴La and ¹⁴⁰Pr from tumor tissue (p > 0.5). The lack of redistribution indicates that the parent radionuclides ¹³⁴Ce and ¹⁴⁰Nd could be considered as long-lived PET-diagnostic matches to therapeutic radionuclides like ¹⁷⁷Lu, ¹⁶¹Tb and ²²⁵Ac when internalizing bioconjugates are employed.

Original language	English
Article number	3863
Journal	Scientific Reports
Volume	12
Number of pages	7
ISSN	2045-2322
DOIs	https://doi.org/10.1038/s41598-022-07147-x
Publication status	Published - 2022

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@article{6c63af669d3545ac8ad5c64b0c6ce403,

title = "PET in vivo generators 134Ce and 140Nd on an internalizing monoclonal antibody probe",

abstract = "The in vivo-generator radionuclides 140Nd (t1/2 = 3.4 d) and 134Ce (t1/2 = 3.2 d) were used to trace a urokinase-type plasminogen activator (uPA)-targeting mouse monoclonal antibody, ATN-291, in U87 MG xenograft tumor-bearing mice. ATN-291 is known to internalize on the uPA/uPA-receptor pair, making it an appropriate targeting vector for investigating the fate of in vivo generator daughters on internalizing probes. Ante-mortem and post-mortem PET imaging at 120 h post-injection gave no indication of redistribution of the positron emitting daughter nuclides 134La and 140Pr from tumor tissue (p > 0.5). The lack of redistribution indicates that the parent radionuclides 134Ce and 140Nd could be considered as long-lived PET-diagnostic matches to therapeutic radionuclides like 177Lu, 161Tb and 225Ac when internalizing bioconjugates are employed.",

author = "Severin, {G. W.} and J. Fonslet and Kristensen, {L. K.} and Nielsen, {C. H.} and Jensen, {A. I.} and A. Kj{\ae}r and Mazar, {A. P.} and K. Johnston and U. K{\"o}ster",

year = "2022",

doi = "10.1038/s41598-022-07147-x",

language = "English",

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journal = "Scientific Reports",

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T1 - PET in vivo generators 134Ce and 140Nd on an internalizing monoclonal antibody probe

AU - Severin, G. W.

AU - Fonslet, J.

AU - Kristensen, L. K.

AU - Nielsen, C. H.

AU - Jensen, A. I.

AU - Kjær, A.

AU - Mazar, A. P.

AU - Johnston, K.

AU - Köster, U.

PY - 2022

Y1 - 2022

N2 - The in vivo-generator radionuclides 140Nd (t1/2 = 3.4 d) and 134Ce (t1/2 = 3.2 d) were used to trace a urokinase-type plasminogen activator (uPA)-targeting mouse monoclonal antibody, ATN-291, in U87 MG xenograft tumor-bearing mice. ATN-291 is known to internalize on the uPA/uPA-receptor pair, making it an appropriate targeting vector for investigating the fate of in vivo generator daughters on internalizing probes. Ante-mortem and post-mortem PET imaging at 120 h post-injection gave no indication of redistribution of the positron emitting daughter nuclides 134La and 140Pr from tumor tissue (p > 0.5). The lack of redistribution indicates that the parent radionuclides 134Ce and 140Nd could be considered as long-lived PET-diagnostic matches to therapeutic radionuclides like 177Lu, 161Tb and 225Ac when internalizing bioconjugates are employed.

AB - The in vivo-generator radionuclides 140Nd (t1/2 = 3.4 d) and 134Ce (t1/2 = 3.2 d) were used to trace a urokinase-type plasminogen activator (uPA)-targeting mouse monoclonal antibody, ATN-291, in U87 MG xenograft tumor-bearing mice. ATN-291 is known to internalize on the uPA/uPA-receptor pair, making it an appropriate targeting vector for investigating the fate of in vivo generator daughters on internalizing probes. Ante-mortem and post-mortem PET imaging at 120 h post-injection gave no indication of redistribution of the positron emitting daughter nuclides 134La and 140Pr from tumor tissue (p > 0.5). The lack of redistribution indicates that the parent radionuclides 134Ce and 140Nd could be considered as long-lived PET-diagnostic matches to therapeutic radionuclides like 177Lu, 161Tb and 225Ac when internalizing bioconjugates are employed.

U2 - 10.1038/s41598-022-07147-x

DO - 10.1038/s41598-022-07147-x

M3 - Journal article

C2 - 35264588

SN - 2045-2322

VL - 12

JO - Scientific Reports

JF - Scientific Reports

M1 - 3863

ER -