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99mTc-HYNIC-Gastrin Peptides: Assisted Coordination of 99mTc by Amino Acid Side Chains Results in Improved Performance Both In Vitro and In Vivo

King, Robert C., Surfraz, M. Bashir-Uddin, Finucane, Ciara, Biagini, Stefano C. G., Blower, Philip J., Mather, Stephen J. (2009) 99mTc-HYNIC-Gastrin Peptides: Assisted Coordination of 99mTc by Amino Acid Side Chains Results in Improved Performance Both In Vitro and In Vivo. Journal of Nuclear Medicine, 50 (4). pp. 591-598. ISSN 0161-5505. (doi:10.2967/jnumed.108.058289) (The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided) (KAR id:40468)

The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided. (Contact us about this Publication)
Official URL
http://dx.doi.org/10.2967/jnumed.108.058289

Abstract

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 99mTc-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 99mTc/99Tc 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.

Item Type: Article
DOI/Identification number: 10.2967/jnumed.108.058289
Uncontrolled keywords: molecular imaging, radiopharmaceuticals, peptides, HYNIC, coordination, technetium
Subjects: Q Science > QC Physics
Divisions: Faculties > Sciences > School of Physical Sciences > Functional Materials Group
Depositing User: Stewart Brownrigg
Date Deposited: 07 Mar 2014 00:05 UTC
Last Modified: 15 Jan 2020 04:05 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/40468 (The current URI for this page, for reference purposes)
Biagini, Stefano C. G.: https://orcid.org/0000-0002-4713-5127
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