Technetium-binding in labelled HYNIC-peptide conjugates: Role of coordinating amino acids

Surfraz, M. Bashir-Uddin; King, Robert C.; Mather, Stephen J.; Biagini, Stefano C. G.; Blower, Philip J.

doi:10.1016/j.jinorgbio.2009.04.007

Cited by 26 publications

(14 citation statements)

References 29 publications

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“…Peptide 3, on the other hand, gave peaks corresponding to both 1 and 2 tricine molecules binding to the technetium-peptide adduct, again with concomitant displacement of 5 protons. This pattern is consistent with that observed in our small-model complex studies (10).…”

Section: Resultssupporting

confidence: 93%

“…We speculated that this might be due to the coordination by neighboring amino acid side chains such as histidine or glutamic acid in the peptide sequence. We therefore investigated this phenomenon in a series of model peptides and found that when histidine is located immediately adjacent to the HYNIC, the peptide showed markedly enhanced stability to cysteine challenge and bovine serum albumin (BSA) binding and contained only 1 tricine; peptides without histidine were less stable and contained 2 tricines (10).…”

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confidence: 99%

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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

King¹,

Surfraz²,

Finucane³

et al. 2009

J Nucl Med

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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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Section: Resultssupporting

confidence: 93%

mentioning

confidence: 99%

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

King¹,

Surfraz²,

Finucane³

et al. 2009

J Nucl Med

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“…In addition, 4 was detected in multiple organs and tissues, which suggests that the labelled tetrazine should be available to react with TCO-conjugates in vivo . These results are consistent with the biodistribution of other HYNIC-tricine derivatives [22–25] and follows a similar trend to that recently reported for the analogous complex derived from a methylated tetrazine derivative [15,26]. …”

Section: Resultssupporting

confidence: 91%

A 99mTc-Labelled Tetrazine for Bioorthogonal Chemistry. Synthesis and Biodistribution Studies with Small Molecule trans-Cyclooctene Derivatives

et al. 2016

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A convenient strategy to radiolabel a hydrazinonicotonic acid (HYNIC)-derived tetrazine with 99mTc was developed, and its utility for creating probes to image bone metabolism and bacterial infection using both active and pretargeting strategies was demonstrated. The 99mTc-labelled HYNIC-tetrazine was synthesized in 75% yield and exhibited high stability in vitro and in vivo. A trans-cyclooctene (TCO)-labelled bisphosphonate (TCO-BP) that binds to regions of active calcium metabolism was used to evaluate the utility of the labelled tetrazine for bioorthogonal chemistry. The pretargeting approach, with 99mTc-HYNIC-tetrazine administered to mice one hour after TCO-BP, showed significant uptake of radioactivity in regions of active bone metabolism (knees and shoulders) at 6 hours post-injection. For comparison, TCO-BP was reacted with 99mTc-HYNIC-tetrazine before injection and this active targeting also showed high specific uptake in the knees and shoulders, whereas control 99mTc-HYNIC-tetrazine alone did not. A TCO-vancomycin derivative was similarly employed for targeting Staphylococcus aureus infection in vitro and in vivo. Pretargeting and active targeting strategies showed 2.5- and 3-fold uptake, respectively, at the sites of a calf-muscle infection in a murine model, compared to the contralateral control muscle. These results demonstrate the utility of the 99mTc-HYNIC-tetrazine for preparing new technetium radiopharmaceuticals, including those based on small molecule targeting constructs containing TCO, using either active or pretargeting strategies.

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“…These low concentrations hamper the analyses of the samples by any available spectroscopic or spectrometric method. However, it has been demonstrated over the last decade that it is possible to obtain ESI-MS spectra of these solutions, particularly, if the technetium concentration is increased [42,43]. Therefore, following this strategy, and by a procedure very similar to that performed here with the Re(I) complex (vide supra), it has been possible to study the transmetallation reaction between the {fac-Tc(CO) 3 } + fragment and the four mammalian Zn-MTs.…”

Section: {Tc(co) 3 } + Binding To the Mammalian Mtsmentioning

confidence: 99%

Rhenium and technetium tricarbonyl, {M(CO)3}+ (M = Tc, Re), binding to mammalian metallothioneins: new insights into chemical and radiopharmaceutical implications

et al. 2014

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This paper deals with the binding of the four mammalian metallothioneins (MTs) to the organometallic metal fragment {fac-M(CO)3}(+) (M = (99)Tc, Re), which is highly promising for the preparation of second-generation radiopharmaceuticals. The study of the transmetallation reaction between zinc and rhenium in Zn7-MT1 by means of UV-vis and CD spectroscopy demonstrated the incorporation of the {fac-Re(CO)3}(+) fragment to the MTs. This reaction should be performed at 70 °C to accelerate the reaction rate, a result that is consistent with the reported reactivity of the rhenium fragment. ESI-TOF MS demonstrated the formation of mixed-metal species as Zn6,{Re(CO)3}-MT, Zn6,{Re(CO)3}2-MT, and Zn5,{Re(CO)3}3-MT, as well as the different reactivity of the four MT isoforms. Hence, Zn-MT3 showed the highest reactivity, in agreement with its high Cu-thionein character, whereas Zn-MT2 exhibited the lowest reactivity, in line with its high Zn-thionein character. The reactivity of the Zn-loaded forms of MT1 and MT4 is intermediate between those of MT3 and MT2. The study of the binding of the {fac-(99)Tc(CO)3}(+) fragment to MTs showed a significant and very interesting different reactivity in relation to rhenium. The transmetallation reaction is much more effective with technetium than with rhenium and significant amounts of mixed Zn x ,{(99)Tc(CO)3} y -MT species were formed with the four MT isoforms whereas only MT3 rendered similar amounts of rhenium derivatives. The results obtained in this study support the possible use of technetium for labelling mammalian metallothioneins and also for possible radiopharmaceutical applications.

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Technetium-binding in labelled HYNIC-peptide conjugates: Role of coordinating amino acids

Cited by 26 publications

References 29 publications

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

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

A 99mTc-Labelled Tetrazine for Bioorthogonal Chemistry. Synthesis and Biodistribution Studies with Small Molecule trans-Cyclooctene Derivatives

Rhenium and technetium tricarbonyl, {M(CO)3}+ (M = Tc, Re), binding to mammalian metallothioneins: new insights into chemical and radiopharmaceutical implications

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Technetium-binding in labelled HYNIC-peptide conjugates: Role of coordinating amino acids

Cited by 26 publications

References 29 publications

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

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

A 99mTc-Labelled Tetrazine for Bioorthogonal Chemistry. Synthesis and Biodistribution Studies with Small Molecule trans-Cyclooctene Derivatives

Rhenium and technetium tricarbonyl, {M(CO)3}+ (M = Tc, Re), binding to mammalian metallothioneins: new insights into chemical and radiopharmaceutical implications

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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

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