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Bioimaging and Biodistribution of the Metal‐Ion‐Controlled Self‐Assembly of PYY 3–36 Studied by SPECT/CT
Author(s) -
Kalomoiri Panagiota,
RodríguezRodríguez Cristina,
Sørensen Kasper K.,
Bergamo Marta,
Saatchi Katayoun,
Häfeli Urs O.,
Jensen Knud J.
Publication year - 2020
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.202000266
Subject(s) - biodistribution , peptide , peptide yy , chemistry , ligand (biochemistry) , spect imaging , in vivo , chelation , metal ions in aqueous solution , metal , receptor , nuclear medicine , in vitro , biochemistry , inorganic chemistry , organic chemistry , medicine , microbiology and biotechnology , neuropeptide y receptor , neuropeptide , biology
The controlled self‐assembly of peptide‐ and protein‐based pharmaceuticals is of central importance for their mode of action and tuning of their properties. Peptide YY 3–36 (PYY 3–36 ) is a 36‐residue peptide hormone that reduces food intake when peripherally administered. Herein, we describe the synthesis of a PYY 3–36 analogue functionalized with a metal‐ion‐binding 2,2’‐bipyridine ligand that enables self‐assembly through metal complexation. Upon addition of Cu II , the bipyridine‐modified PYY 3–36 peptide binds stoichiometric quantities of metal ions in solution and contributes to the organization of higher‐order assemblies. In this study, we aimed to explore the size effect of the self‐assembly in vivo by using non‐invasive quantitative single‐photon emission computed tomography/computed tomography (SPECT/CT) imaging. For this purpose, bipyridine‐modified PYY 3–36 was radiolabeled with a chelator holding 111 In III , followed by the addition of Cu II to the bipyridine ligand. SPECT/CT imaging and biodistribution studies showed fast renal clearance and accumulation in the kidney cortex. The radiolabeled bipyridyl‐PYY 3–36 conjugates with and without Cu II presented a slightly slower excretion 1 h post injection compared to the unmodified‐PYY 3–36 , thus demonstrating that higher self‐assemblies of the peptide might have an effect on the pharmacokinetics.