99mTc-HYNIC-Gastrin Peptides: Assisted Coordination of 99mTc by Amino Acid Side Chains Results in Improved Performance Both In Vitro and In Vivo.
J Nucl Med
; 50(4): 591-8, 2009 Apr.
Article
em En
| MEDLINE
| ID: mdl-19289435
UNLABELLED: The aim of this study was to determine the effects of assisted coordination by amino acids such as histidine and glutamic acid on the function of (99m)Tc-labeled gastrin peptide-hydrazinonicotinamide (HYNIC) conjugates and their ability to target cholecystokinin-R in small-animal models. METHODS: Three peptide-HYNIC conjugates containing the -AYGWMDF-NH2 C-terminal sequence and combinations of histidine, glutamic acid, and glycine were synthesized, radiolabeled with (99m)Tc/(99)Tc using either tricine or ethylenediaminediacetic acid as a coligand, and analyzed by the high-performance liquid chromatography and liquid chromatography-mass spectrometric techniques. Stability, receptor binding, and internalization and in vivo targeting in AR42J-bearing mice were assessed. RESULTS: When radiolabeling was performed using tricine as a coligand, the insertion of a histidine residue near the HYNIC residue resulted in the displacement of one molecule of tricine from the coordination sphere, a reduction in the number of radiolabeled species formed, an improvement in the in vitro stability, an increase in the rate of radiopeptide internalization, and a significant improvement in tumor uptake in vivo. When radiolabeling was performed using ethylenediaminediacetic acid as a coligand, no effect on coligand binding, homogeneity, or in vitro stability was observed but a significant improvement in the internalization in vitro and tumor uptake in vivo was again found. All of the complexes formed showed similar receptor affinity in competitive radioligand binding assays. CONCLUSION: The insertion of histidine into the sequence of peptide-HYNIC conjugates can result in more stable, more homogeneous complexes that show improvements in tumor-targeting performance both in vitro and in vivo.
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Base de dados:
MEDLINE
Assunto principal:
Neoplasias Pancreáticas
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Aumento da Imagem
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Compostos Radiofarmacêuticos
Limite:
Animals
Idioma:
En
Ano de publicação:
2009
Tipo de documento:
Article