Open Access

Reduction of renal activity retention of radiolabeled albumin binding domain‑derived affinity proteins using a non‑residualizing label strategy compared with a cleavable glycine‑leucine‑glycine‑lysine‑linker

  • Authors:
    • Fanny Lundmark
    • Anzhelika Vorobyeva
    • Yongsheng Liu
    • Sarah Lindbo
    • Tianqi Xu
    • Maryam Oroujeni
    • Sara S. Rinne
    • Ulrika Rosenström
    • Javad Garousi
  • View Affiliations

  • Published online on: December 28, 2023     https://doi.org/10.3892/mmr.2023.13155
  • Article Number: 32
  • Copyright: © Lundmark et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The feasibility of targeted imaging and therapy using radiolabeled albumin‑binding domain‑derived affinity proteins (ADAPTs) has been demonstrated. However, high renal uptake of radioactivity limits the maximum tolerated dose. Successful reduction of renal retention of radiolabeled Fab fragments has been demonstrated by incorporating a cleavable linker between the targeting agent and the radiometal chelator. The present study investigated if the introduction of a glycine‑leucine‑glycine‑lysine (GLGK)‑linker would reduce the kidney uptake of radiolabeled ADAPT6 and also compared it with the non‑residualizing [125I]I‑[(4‑hydroxyphenyl)ethyl]maleimide ([125I]I‑HPEM) labeling strategy. GLGK was site‑specifically coupled to human epidermal growth factor receptor 2 (HER2)‑targeting ADAPT6. Conjugates without the cleavable linker were used as controls and all constructs were labeled with lutetium‑177 (177Lu). [125I]I‑HPEM was coupled to ADAPT6 at the C‑terminus. Biodistribution of all constructs was evaluated in NMRI mice 4 h after injection. Specific binding to HER2‑expressing cells in vitro was demonstrated for all constructs. No significant difference in kidney uptake was observed between the [177Lu]Lu‑2,2',2”,2”'‑(1,4,7,10‑tetraazacyclododecane‑1,4,7,10‑tetrayl)tetraacetic acid‑GLGK‑conjugates and the controls. The renal activity of [125I]I‑HPEM‑ADAPT6 was significantly lower compared with all other constructs. In conclusion, the incorporation of the cleavable GLGK‑linker did not result in lower renal retention. Therefore, the present study emphasized that, in order to achieve a reduction of renal retention, alternative molecular design strategies may be required for different targeting agents.
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February-2024
Volume 29 Issue 2

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Spandidos Publications style
Lundmark F, Vorobyeva A, Liu Y, Lindbo S, Xu T, Oroujeni M, Rinne SS, Rosenström U and Garousi J: Reduction of renal activity retention of radiolabeled albumin binding domain‑derived affinity proteins using a non‑residualizing label strategy compared with a cleavable glycine‑leucine‑glycine‑lysine‑linker. Mol Med Rep 29: 32, 2024
APA
Lundmark, F., Vorobyeva, A., Liu, Y., Lindbo, S., Xu, T., Oroujeni, M. ... Garousi, J. (2024). Reduction of renal activity retention of radiolabeled albumin binding domain‑derived affinity proteins using a non‑residualizing label strategy compared with a cleavable glycine‑leucine‑glycine‑lysine‑linker. Molecular Medicine Reports, 29, 32. https://doi.org/10.3892/mmr.2023.13155
MLA
Lundmark, F., Vorobyeva, A., Liu, Y., Lindbo, S., Xu, T., Oroujeni, M., Rinne, S. S., Rosenström, U., Garousi, J."Reduction of renal activity retention of radiolabeled albumin binding domain‑derived affinity proteins using a non‑residualizing label strategy compared with a cleavable glycine‑leucine‑glycine‑lysine‑linker". Molecular Medicine Reports 29.2 (2024): 32.
Chicago
Lundmark, F., Vorobyeva, A., Liu, Y., Lindbo, S., Xu, T., Oroujeni, M., Rinne, S. S., Rosenström, U., Garousi, J."Reduction of renal activity retention of radiolabeled albumin binding domain‑derived affinity proteins using a non‑residualizing label strategy compared with a cleavable glycine‑leucine‑glycine‑lysine‑linker". Molecular Medicine Reports 29, no. 2 (2024): 32. https://doi.org/10.3892/mmr.2023.13155