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@ARTICLE{Brandt:301502,
author = {F. Brandt and M. Ullrich and M. Laube and R. Löser and J.
Kotzerke and K. Kopka$^*$ and J. Pietzsch and J. van den
Hoff and R. Wodtke},
title = {{D}eciphering the {T}umor {U}ptake of {H}eterobivalent
({SST}2/{A}lbumin) [64{C}u]{C}u-{NODAGA}-c{LAB}-{TATE}s.},
journal = {Journal of medicinal chemistry},
volume = {68},
number = {11},
issn = {0095-9065},
address = {Washington, DC},
publisher = {ACS},
reportid = {DKFZ-2025-01041},
pages = {12029-12046},
year = {2025},
note = {2025 Jun 12;68(11):12029-12046},
abstract = {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.},
cin = {DD01},
ddc = {610},
cid = {I:(DE-He78)DD01-20160331},
pnm = {899 - ohne Topic (POF4-899)},
pid = {G:(DE-HGF)POF4-899},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:40393943},
doi = {10.1021/acs.jmedchem.5c00890},
url = {https://inrepo02.dkfz.de/record/301502},
}