Synthesis, radiolabelling and biological characteristics of a bombesin peptide analog as a tumor imaging agent.
BACKGROUND
Several human cancers, including small cell lung, prostate, breast, gastric, colon and pancreatic cancers, express receptors for bombesin-like peptides. Bombesin (BN) peptides that bind specifically to these receptors are useful for detection of bombesin receptor-expressing cancers in vivo. A new 99mTc-labelled-BN peptide for targeting bombesin receptor-expressing cancers was prepared and characterized.


METHODS
MAG3-coupled BN peptide (MAG3-BN) was prepared by solid-phase synthesis and radiolabelled with 99mTc by an exchange method. In vitro cell binding assays were conducted on human breast cancer cell lines, MDA-MB-231 and MCF-7. In vivo biodistribution studies were performed in normal and nude mice bearing bombesin receptor-positive tumors.


RESULTS
Radiolabelling of MAG3-BN with 99mTc produces a single radioactive species (> 95%). In vitro cell-binding indicated the affinity and specificity of 99mTc-MAG3-BN towards bombesin receptors. In vivo biodistribution in mice demonstrated that 99mTc-MAG3-BN cleared rapidly from the blood and most non-targeted tissues and was excreted mainly via the kidneys. Uptake in bombesin receptor-positive tissues and in the tumor was low to moderate.


CONCLUSIONS
99mTc-MAG3-BN displays good radiolabelling together with certain favorable biological characteristics and might be a useful peptide radiopharmaceutical in the detection of bombesin receptor-expressing cancers in vivo.
Okarvi
S M
SM
Cyclotron and Radiopharmaceuticals Department, King Faisal Specialist Hospital and Research Centre, MBC-03, PO Box 3354, Riyadh 11211, KSA. sokarvi@kfshrc.edu.sa
al-Jammaz
I
I
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D001839:Bombesin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000493:pharmacokinetics; D001943:Breast Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism; D003545:Cysteine / Q000737:chemistry; D005260:Female; D006801:Humans; D007553:Isotope Labeling; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D018004:Receptors, Bombesin / Q000037:antagonists & inhibitors / Q000378:metabolism; D017556:Technetium Compounds / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D017263:Technetium Tc 99m Mertiatide / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured
C476676:99mTc-MAG3-Pro3-BN; D019275:Radiopharmaceuticals; D018004:Receptors, Bombesin; D017556:Technetium Compounds; D017263:Technetium Tc 99m Mertiatide; D003545:Cysteine; D001839:Bombesin