Journal Article

DKFZ-2025-01041

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Deciphering the Tumor Uptake of Heterobivalent (SST2/Albumin) [64Cu]Cu-NODAGA-cLAB-TATEs.

Brandt, F. ; Ullrich, M. ; Laube, M. ; Löser, R. ; Kotzerke, J. ; Kopka, K.DKFZ* ; Pietzsch, J. ; van den Hoff, J. ; Wodtke, R.

2025
ACS Washington, DC

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.

Note: 2025 Jun 12;68(11):12029-12046

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Contributing Institute(s):

1. DKTK Koordinierungsstelle Dresden (DD01)

Research Program(s):

1. 899 - ohne Topic (POF4-899) (POF4-899)

Appears in the scientific report 2025

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Chemical Reactions ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; Index Chemicus ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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