RT Journal Article
SR Electronic
T1 <sup>99m</sup>Tc-HYNIC-Gastrin Peptides: Assisted Coordination of <sup>99m</sup>Tc by Amino Acid Side Chains Results in Improved Performance Both In Vitro and In Vivo
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 591
OP 598
DO 10.2967/jnumed.108.058289
VO 50
IS 4
A1 King, Robert
A1 Surfraz, M. Bashir-Uddin
A1 Finucane, Ciara
A1 Biagini, Stefano C.G.
A1 Blower, Philip J.
A1 Mather, Stephen J.
YR 2009
UL http://jnm.snmjournals.org/content/50/4/591.abstract
AB 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.