Structural modifications of ⁹⁹mTc-labelled bombesin-like peptides for optimizing pharmacokinetics in prostate tumor targeting.

Abstract

PURPOSE:

The main goal of the present study was to investigate the importance of the addition of a positively charged aa in the naturally occurring bombesin (BN) peptide for its utilization as radiodiagnostic agent, taking into consideration the biodistribution profile, the pharmacokinetic characteristics and the tumor targeting ability.

METHODS:

Two BN-derivatives of the general structure [M-chelator]-(spacer)-BN(2-14)-NH(2), where M: (99m)Tc or (185/187)Re, chelator: Gly-Gly-Cys-, spacer: -(arginine)(3)-, M-BN-A; spacer: -(ornithine)(3)-, M-BN-O; have been prepared and evaluated as tumor imaging agents.

RESULTS:

The peptides under study presented high radiolabelling efficiency (>98%), significant stability in human plasma (>60% intact radiolabelled peptide after 1h incubation) and comparable receptor binding affinity with the standard [(125)I-Tyr(4)]-BN. Their internalization rates in the prostate cancer PC-3 cells differed, although the amount of internalized peptide was the same. The biodistribution and the dynamic γ-camera imaging studies in normal and PC-3 tumor-bearing SCID mice have shown significant tumor uptake, combined with fast blood clearance, through the urinary pathway.

CONCLUSION:

The addition of the charged aa spacer in the BN structure was advantageous for biodistribution, pharmacokinetics and tumor targeting ability, because it reduced the upper abdominal radioactivity levels and increased tumor/normal tissue contrast ratios.

• Authors: Christos C Liolios, Eirini A Fragogeorgi, Christos Zikos, George Loudos, Stavros Xanthopoulos, Penelope Bouziotis, Maria Paravatou-Petsotas, Evangelia Livaniou, Alexandra D Varvarigou, Gregory B Sivolapenko
• Journal: International journal of pharmaceutics (Int J Pharm) Vol. 430 Issue 1-2 Pg. 1-17 (Jul 01 2012) ISSN: 1873-3476 [Electronic] Netherlands
• PMID: 22459664 (Publication Type: Journal Article)
• Copyright: Copyright © 2012 Elsevier B.V. All rights reserved.

Chemical References

• Ligands
• Peptides
• Radiopharmaceuticals
• Receptors, Bombesin
• Technetium
• Bombesin

Topics

• Animals
• Biological Transport
• Bombesin (analogs & derivatives, blood, pharmacokinetics)
• Cell Line, Tumor
• Chromatography, High Pressure Liquid
• Chromatography, Reverse-Phase
• Female
• Humans
• Ligands
• Male
• Mice
• Mice, SCID
• Peptides (blood, pharmacokinetics)
• Prostatic Neoplasms (diagnostic imaging, metabolism)
• Protein Binding
• Protein Conformation
• Protein Stability
• Radionuclide Imaging
• Radiopharmaceuticals (blood, pharmacokinetics)
• Receptors, Bombesin (metabolism)
• Technetium (blood, pharmacokinetics)
• Tissue Distribution
• Video Recording