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.
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.
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.
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.
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"This analogue showed good GRP-R-targeting in mice and excretion via the renal pathway   . Neutral 99m Tc V O 3+ -complexes are also obtained by coupling tripeptide N 3 S-donors to BB or BB(7-14), either directly or via a spacer      . For example, 99m Tc-RP527, a BB(7-14) analogue linked at the N-terminus via a glycine-5-aminovaleric acid spacer to the tri-peptide chelator, dimethylglycyl-L-ser-L-cys, reached a 2%ID/g at 1 h pi in PC-3 xenografts in SCID (severe combined immunodeficiency) mice   . "
[Show abstract][Hide abstract] ABSTRACT: The fact that a number of common human tumours, including those of breast and prostate, express increased levels of the gastrin-releasing peptide receptor (GRP-R) means that this receptor is a potential target for peptide receptor mediated scintigraphy and targeted radionuclide therapy. Although clinical application is yet in its infancy, there is a considerable literature on preclinical studies aimed at developing suitable radioligands for potential clinical application. This brief review provides an overview of this research and also describes some of the limited clinical studies that have been published.
"DOTA can also be used for labelling with positron emitters such as 64 Cu or 68 Ga. For labelling with 99m Tc, bifunctional coupling agents may be used such as MAG 3    or HYNIC   . "
[Show abstract][Hide abstract] ABSTRACT: Radiolabelled peptides are used for specific targeting of receptors (over-)expressed by tumour cells. Dependent on the kind of labelling and the radionuclide used, these compounds may be utilised for imaging or for therapy. A concise overview is provided on basic principles of designing and developing radiopeptides for these applications. Furthermore, clinical application of these compounds for imaging and therapy is described. Advantages of the method compared to other techniques (such as the use of radiolabelled antibodies or antibody fragments) are discussed as well as pitfalls and limitations.
[Show abstract][Hide abstract] ABSTRACT: In an effort to develop a peptide-based radiopharmaceutical for the detection of breast cancer, we have prepared an analog of alphaM2 peptide, modified to incorporate an N3S chelate system. Mercaptoacetyltriglycine (MAG)(3)-derivatized alphaM2 peptide was prepared by solid-phase synthesis and radiolabeled with (99m)Tc by an exchange method. In vitro cell-binding on human breast cancer cell lines, MDA-MB-231 and MCF-7, indicated the affinity and specificity of (99m)Tc-MAG(3)-alphaM2 toward breast cancer cells. Additionally, the radiolabeled peptide showed rapid internalization into human breast cancer cells. In vivo biodistribution in mice showed that the radiolabeled peptide cleared rapidly from the blood and most non-target tissues and was excreted significantly via the kidneys. Uptake of (99m)Tc-MAG(3)-alphaM2 in the tumor was moderate. The radiochemical and in vitro and in vivo characterization indicates that the radiolabeled peptide has certain favorable properties and it might be a useful radiopharmaceutical for the detection of breast cancer in vivo.
No preview · Article · Jul 2004 · European Journal of Allergy and Clinical Immunology