TY  - JOUR
AU  - Brandt, Florian
AU  - Ullrich, Martin
AU  - Laube, Markus
AU  - Löser, Reik
AU  - Kotzerke, Jörg
AU  - Kopka, Klaus
AU  - Pietzsch, Jens
AU  - van den Hoff, Jörg
AU  - Wodtke, Robert
TI  - Deciphering the Tumor Uptake of Heterobivalent (SST2/Albumin) [64Cu]Cu-NODAGA-cLAB-TATEs.
JO  - Journal of medicinal chemistry
VL  - 68
IS  - 11
SN  - 0095-9065
CY  - Washington, DC
PB  - ACS
M1  - DKFZ-2025-01041
SP  - 12029-12046
PY  - 2025
N1  - 2025 Jun 12;68(11):12029-12046
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - pmid:40393943
DO  - DOI:10.1021/acs.jmedchem.5c00890
UR  - https://inrepo02.dkfz.de/record/301502
ER  -