Glycated 99m Tc-Tricarbonyl-Labeled Peptide Conjugates for Tumor Targeting by 'Click-to-Chelate'
| Autor: | Thomas L. Mindt, Karolin Römhild, Christiane A. Fischer |
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| Rok vydání: | 2016 |
| Předmět: |
Pharmacology
chemistry.chemical_classification 010405 organic chemistry media_common.quotation_subject Organic Chemistry Bombesin Peptide 010402 general chemistry Glucuronic acid 01 natural sciences Biochemistry In vitro Glycopeptide 0104 chemical sciences chemistry.chemical_compound chemistry Drug Discovery Molecular Medicine General Pharmacology Toxicology and Pharmaceutics Internalization Peptide sequence Conjugate media_common |
| Zdroj: | ChemMedChem. 12:66-74 |
| ISSN: | 1860-7179 |
| DOI: | 10.1002/cmdc.201600485 |
| Popis: | Attaching polar pharmacological modifiers to molecular imaging probes is a common strategy to modulate their pharmacokinetic profiles to improve such parameters as the clearance rate of radiotracers and/or metabolites, and to enhance signal-to-background ratios. We combined the tumor-targeting peptide sequence of bombesin (BBN) with glucuronic acid and the single-photon emission computed tomography (SPECT) radionuclide 99m Tc by the "click-to-chelate" methodology. The 99m Tc-tricarbonyl-labeled glucuronated BBN conjugate was compared with a reference compound lacking the carbohydrate. The radiolabeled conjugates displayed similar characteristics in vitro (cell internalization, receptor affinity), but the hydrophilicity of the glycated version was significantly increased. While the tumor uptake of the two radioconjugates in xenografted mice was similar, the glycated peptide exhibited unexpected higher uptake in organs of the hepatobiliary excretion pathway than the more lipophilic reference compound. Control experiments suggest that this may be the result of unspecific accumulation of metabolites in which the glucuronic acid moiety does not act as an innocent pharmacological modifier. |
| Databáze: | OpenAIRE |
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