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Deciphering the tumor uptake of heterobivalent (SST2/Albumin) (64Cu)Cu-NODAGA-cLAB-TATEs

Radioligands with albumin-binding moieties exhibit a great potential for the treatment of tumor diseases owing to the general finding of an increased integral tumor uptake compared to radioligands without such moieties. However, the reasons for this pharmacokinetic behavior are less explored. Herein...

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Main Authors: Brandt, Florian (Author) , Ullrich, Martin (Author) , Laube, Markus (Author) , Löser, Reik (Author) , Kotzerke, Jörg (Author) , Kopka, Klaus (Author) , Pietzsch, Jens (Author) , Hoff, Jörg van den (Author) , Wodtke, Robert (Author)
Format: Article (Journal)
Language:English
Published: May 20, 2025
In: Journal of medicinal chemistry
Year: 2025, Volume: 68, Issue: 11, Pages: 12029-12046
ISSN:1520-4804
DOI:10.1021/acs.jmedchem.5c00890
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.1021/acs.jmedchem.5c00890
Verlag, kostenfrei, Volltext: https://pubs.acs.org/doi/10.1021/acs.jmedchem.5c00890
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Author Notes:Florian Brandt, Martin Ullrich, Markus Laube, Reik Löser, Jörg Kotzerke, Klaus Kopka, Jens Pietzsch, Jörg van den Hoff, and Robert Wodtke
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Summary:Radioligands with albumin-binding moieties exhibit a great potential for the treatment of tumor diseases owing to the general finding of an increased integral tumor uptake compared to radioligands without such moieties. However, the reasons for this pharmacokinetic behavior are less explored. Herein, we focused on identifying potential mechanisms for our previously developed heterobivalent (SST2/albumin) [64Cu]Cu-NODAGA-cLAB-TATEs. For this purpose, we designed two novel derivatives that show either negligible binding to albumin or lack the SST2-targeting capability. Based on the in vivo results, we hypothesize that binding of the albumin-bound radioligand to SST2 in addition to that of the free radioligand causes the increased tumor uptake. This is supported by saturation binding analyses in the presence of albumin and compartment modeling considerations. Overall, the results of this study provide a first tentative explanation for the phenomenon of increased tumor uptake for albumin-binding radioligands, which may support the prospective design of such radioligands.
Item Description:Im Titel ist 2 bei (SST2/Albumin) tiefgestellt, [64Cu] steht in eckigen Klammern, 64 ist dabei hochgestellt
Gesehen am 29.10.2025
Physical Description:Online Resource
ISSN:1520-4804
DOI:10.1021/acs.jmedchem.5c00890

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