Dataset Information

Synthesis, characterization and biological studies of rhenium, technetium-99m and rhenium-188 pentapeptides.

ABSTRACT: A pentapeptide macrocyclic ligand, KYCAR (lysyl-tyrosyl-cystyl-alanyl-arginine), has been designed as a potential chelating ligand for SPECT imaging and therapeutic in vivo agents. This study shows the synthesis and characterization of KYCAR complexes containing nonradioactive rhenium, ^99mTc, or ¹⁸⁸Re. The metal complexes were also biologically evaluated to determine in vivo distribution in healthy mice. The overall goals of this project were (1) to synthesize the Tc/Re pentapeptide complexes, (2) to identify spectroscopic methods for characterization of syn versus anti rhenium peptide complexes, (3) to analyze the ex vivo stability, and (4) to assess the biological properties of the [^99mTc]TcO-KYCAR and [¹⁸⁸Re]ReO-KYCAR complexes in vivo. Details on these efforts are provided below.

Methods

^NatRe/^99mTc/¹⁸⁸ReO-KYCAR complexes were synthesized, and macroscopic species were characterized via HPLC, IR, NMR, and CD. These characterization data were compared to the crystallographic data of ReO-KYC to assist in the assignment of diastereomers and to aid in the determination of the structure of the complex.

Results

The radiometal complexes were synthesized with high purity (>95%). HPLC, IR, NMR and CD data on the macroscopic ^natReO-KYCAR complexes confirm the successful complexation as well as the presence of two diastereomers in syn and anticonformations. Tracer level complexes show favorable stabilities ex vivo for 2+ h.

Conclusion

Macroscopic metal complexes form diastereomers with the KYCAR ligand; however, this phenomenon is not readily observed on the tracer level due to the rapid interconversion. It was determined through pK_a measurements that the macroscopic ^natReO-KYCAR complex is 0 at physiological pH. The [^99mTc]TcO-KYCAR is stable in vitro while the [¹⁸⁸Re]ReO-KYCAR shows 50% decomposition in PBS and serum. Biologically, the tracer level complexes clear through the hepatobiliary pathway. Some decomposition of both tracers is evident by uptake in the thyroid and stomach.

SUBMITTER: Sanders VA

PROVIDER: S-EPMC6451878 | biostudies-literature | 2019 Jan - Feb

REPOSITORIES: biostudies-literature

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Publications

Synthesis, characterization and biological studies of rhenium, technetium-99m and rhenium-188 pentapeptides.

Sanders Vanessa A VA Iskhakov David D Abdel-Atti Dalya D Devany Matthew M Neary Michelle C MC Czerwinski Ken R KR Francesconi Lynn C LC

Nuclear medicine and biology 20181112

A pentapeptide macrocyclic ligand, KYCAR (lysyl-tyrosyl-cystyl-alanyl-arginine), has been designed as a potential chelating ligand for SPECT imaging and therapeutic in vivo agents. This study shows the synthesis and characterization of KYCAR complexes containing nonradioactive rhenium, <sup>99m</sup>Tc, or <sup>188</sup>Re. The metal complexes were also biologically evaluated to determine in vivo distribution in healthy mice. The overall goals of this project were (1) to synthesize the Tc/Re pen ...[more]

PMID: 30578134

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Project description:Background and purposeNiosomes are nonionic surfactant-based vesicles that exhibit certain unique features which make them favorable nanocarriers for sustained drug delivery in cancer therapy. Biodistribution studies are critical in assessing if a nanocarrier system has preferential accumulation in a tumor by enhanced permeability and retention effect. Radiolabeling of nanocarriers with radioisotopes such as Technetium-99m (99mTc) will allow for the tracking of the nanocarrier noninvasively via nuclear imaging. The purpose of this study was to formulate, characterize, and optimize 99mTc-labeled niosomes.MethodsNiosomes were prepared from a mixture of sorbitan monostearate 60, cholesterol, and synthesized D-?-tocopherol polyethylene glycol 1000 succinate-diethylenetriaminepentaacetic acid (synthesis confirmed by 1H and 13C nuclear magnetic resonance spectroscopy). Niosomes were radiolabeled by surface chelation with reduced 99mTc. Parameters affecting the radiolabeling efficiency such as concentration of stannous chloride (SnCl2·H2O), pH, and incubation time were evaluated. In vitro stability of radiolabeled niosomes was studied in 0.9% saline and human serum at 37°C for up to 8 hours.ResultsNiosomes had an average particle size of 110.2±0.7 nm, polydispersity index of 0.229±0.008, and zeta potential of -64.8±1.2 mV. Experimental data revealed that 30 µg/mL of SnCl2·H2O was the optimal concentration of reducing agent required for the radiolabeling process. The pH and incubation time required to obtain high radiolabeling efficiency was pH 5 and 15 minutes, respectively. 99mTc-labeled niosomes exhibited high radiolabeling efficiency (>90%) and showed good in vitro stability for up to 8 hours.ConclusionTo our knowledge, this is the first study published on the surface chelation of niosomes with 99mTc. The formulated 99mTc-labeled niosomes possessed high radiolabeling efficacy, good stability in vitro, and show good promise for potential use in nuclear imaging in the future.

Dataset Information

Synthesis, characterization and biological studies of rhenium, technetium-99m and rhenium-188 pentapeptides.

Methods

Results

Conclusion

Publications

Synthesis, characterization and biological studies of rhenium, technetium-99m and rhenium-188 pentapeptides.

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