2. Academic Validation
  3. The Effects of an Albumin Binding Moiety on the Targeting and Pharmacokinetics of an Integrin αvβ6-Selective Peptide Labeled with Aluminum [18F]Fluoride

The Effects of an Albumin Binding Moiety on the Targeting and Pharmacokinetics of an Integrin αvβ6-Selective Peptide Labeled with Aluminum [18F]Fluoride

  • Mol Imaging Biol. 2020 Dec;22(6):1543-1552. doi: 10.1007/s11307-020-01500-0.
Sven H Hausner 1,  Nadine Bauer 1,  Ryan A Davis 2,  Tanushree Ganguly 1,  Sarah Y C Tang 1,  Julie L Sutcliffe 3 4 5
Affiliations

Affiliations

  • 1 Division of Hematology/Oncology, Department of Internal Medicine, University of California Davis, Sacramento, CA, USA.
  • 2 Department of Biomedical Engineering, University of California Davis, Davis, CA, USA.
  • 3 Division of Hematology/Oncology, Department of Internal Medicine, University of California Davis, Sacramento, CA, USA. [email protected].
  • 4 Department of Biomedical Engineering, University of California Davis, Davis, CA, USA. [email protected].
  • 5 Center for Molecular and Genomic Imaging, University of California Davis, Davis, CA, USA. [email protected].
PMID: 32383076 DOI: 10.1007/s11307-020-01500-0
Abstract

Purpose: The αvβ6-BP peptide selectively targets the Integrin αvβ6, a cell surface receptor recognized as a prognostic indicator for several challenging malignancies. Given that the 4-[18F]fluorobenzoyl (FBA)-labeled peptide is a promising PET imaging agent, radiolabeling via aluminum [18F]fluoride chelation and introduction of an albumin binding moiety (ABM) have the potential to considerably simplify radiochemistry and improve the pharmacokinetics by increasing biological half-life.

Procedures: The Peptides NOTA-αvβ6-BP (1) and NOTA-K(ABM)-αvβ6-BP (2) were synthesized on solid phase, radiolabeled with aluminum [18F]fluoride, and evaluated in vitro (Integrin ELISA, albumin binding, cell studies) and in vivo in mouse models bearing paired DX3puroβ6 [αvβ6(+)]/DX3puro [αvβ6(-)], and for [18F]AlF 2, BxPC-3 [αvβ6(+)] cell xenografts (PET imaging, biodistribution).

Results: The Peptides were radiolabeled in 23.0 ± 5.7 % and 22.1 ± 4.4 % decay-corrected radiochemical yield, respectively, for [18F]AlF 1 and [18F]AlF 2. Both demonstrated excellent affinity and selectivity for Integrin αvβ6 by ELISA (IC50(αvβ6) = 3-7 nM vs IC50(αvβ3) > 10 μM) and in cell binding studies (51.0 ± 0.7 % and 47.2 ± 0.7 % of total radioactivity bound to DX3puroβ6 cells at 1 h, respectively, vs. ≤ 1.2 % to DX3puro for both compounds). The radiotracer [18F]AlF 1 bound to human serum at 16.3 ± 1.9 %, compared to 67.5 ± 1.0 % for the ABM-containing [18F]AlF 2. In vivo studies confirmed the effect of the ABM on blood circulation (≤ 0.1 % ID/g remaining in blood for [18F]AlF 1 as soon as 1 h p.i. vs. > 2 % ID/g for [18F]AlF 2 at 6 h p.i.) and higher αvβ6(+) tumor uptake (4 h: DX3puroβ6; [18F]AlF 1: 3.0 ± 0.7 % ID/g, [18F]AlF 2: 7.2 ± 0.7 % ID/g; BxPC-3; [18F]AlF 2: 10.2 ± 0.1 % ID/g).

Conclusion: Both compounds were prepared using standard chemistries; affinity and selectivity for Integrin αvβ6 in vitro remained unaffected by the albumin binding moiety. In vivo, the albumin binding moiety resulted in prolonged circulation and higher αvβ6-targeted uptake.

Keywords

Albumin; Albumin binding moiety; Aluminum [18F]fluoride; Blood circulation; Integrin αvβ6; PET imaging; Peptide.

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