Titel
Sorbitol as a Polar Pharmacological Modifier to Enhance the Hydrophilicity of 99mTc-Tricarbonyl-Based Radiopharmaceuticals
Autor*in
Theresa Balber
Ludwig Boltzmann Institute Applied Diagnostics, General Hospital of Vienna
Autor*in
Katarina Benčurová
Ludwig Boltzmann Institute Applied Diagnostics, General Hospital of Vienna
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Abstract
The organometallic technetium-99m tricarbonyl core, [99mTc][Tc(CO)3(H2O)3]+, is a versatile precursor for the development of radiotracers for single photon emission computed tomography (SPECT). A drawback of the 99mTc-tricarbonyl core is its lipophilicity, which can influence the pharmacokinetic properties of the SPECT imaging probe. Addition of polar pharmacological modifiers to 99mTc-tricarbonyl conjugates holds the promise to counteract this effect and provide tumor-targeting radiopharmaceuticals with improved hydrophilicities, e.g., resulting in a favorable fast renal excretion in vivo. We applied the “Click-to-Chelate” strategy for the assembly of a novel 99mTc-tricarbonyl labeled conjugate made of the tumor-targeting, modified bombesin binding sequence [Nle14]BBN(7–14) and the carbohydrate sorbitol as a polar modifier. The 99mTc-radiopeptide was evaluated in vitro with PC-3 cells and in Fox-1nu mice bearing PC-3 xenografts including a direct comparison with a reference conjugate lacking the sorbitol moiety. The glycated 99mTc-tricarbonyl peptide conjugate exhibited an increased hydrophilicity as well as a retained affinity toward the Gastrin releasing peptide receptor and cell internalization properties. However, there was no significant difference in vivo in terms of pharmacokinetic properties. In particular, the rate and route of excretion was unaltered in comparison to the more lipophilic reference compound. This could be attributed to the intrinsic properties of the peptide and/or its metabolites. We report a novel glycated (sorbitol-containing) alkyne substrate for the “Click-to-Chelate” methodology, which is potentially of general applicability for the development of 99mTc-tricarbonyl based radiotracers displaying an enhanced hydrophilicity.
Stichwort
99mTc-tricarbonylbombesinclick-to-chelateglycationsorbitolpharmacological modifierhydrophilicityradiolabeled peptidesSPECT
Objekt-Typ
Sprache
Englisch [eng]
Persistent identifier
Erschienen in
Titel
Molecules
Band
25
Ausgabe
11
ISSN
1420-3049
Erscheinungsdatum
2020
Publication
MDPI AG
Erscheinungsdatum
2020
Zugänglichkeit
Rechteangabe
© 2020 by the authors

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