Background

[PubMed]

Bombesin (BBN or BN)-like peptide is an analog of human gastrin-releasing peptide (GRP) that binds to GRP receptors (GRP-R) (1). Both GRP and BN share an amidated C-terminus sequence homology of seven amino acids (Trp-Ala-Val-Gly-His-Leu-Met-NH₂). BN peptides induce such biological responses as secretion of adrenal, pituitary, and gastrointestinal hormones; gastric acid secretion; modulation of neuronal firing rate; and regulation of smooth muscle contraction (2, 3). BN-Related peptide receptors can be divided into four subtypes: GRP-R (BB2, BRS-2), neuromedin B receptor (NMB-R, BB1, BRS-1), the orphan receptor BB3-R (BRS-3), and the amphibian receptor BB4-R (1). Several human cancers, such as prostate, breast, lung, colon, and pancreatic cancers, overexpress receptors for BN-like peptides. The BN-like peptides have been radiolabeled with different radionuclides for in vivo imaging of various cancers (4-7).

Litorin (pGlu-Gln-Trp-Ala-Val-Gly-His-Phe-Met-NH₂), an amphibian BN peptide derivative, is found to stimulate the contraction of smooth muscle, to stimulate gastrin, gastric acid, and pancreatic secretion, and to suppress the nutriment in in vivo experiments (1). ^99mTc-Litorin was developed for non-invasive imaging of tumors with overexpressed GRP-R (8).

Synthesis

[PubMed]

Durkan et al. (8) reported the synthesis of ^99mTc-litorin by incubation of 5 μg litorin, 25 μg SnCl₂, and 55.5 MBq (1.5 mCi ) Na[^99mTcO₄] (pH 3.0) for 25 min at room temperature. Radiochemical yield was >95%.

In Vitro Studies: Testing in Cells and Tissues

[PubMed]

The in vitro solution stability of ^99mTc-litorin was tested by incubating the radiolabeled peptide in buffer solution with 500 or 1,000 molar excess of cysteine at 37ºC for 1 h (8). No significant degradation of ⁹⁹Tc-litorin was observed at 500 molar excess of cysteine; 1,000 molar excess of cysteine displaced 16.8 ± 2.7% of radioactivity from litorin, which suggests that the bond strength of ^99mTc to litorin is high. Serum stability was 87.4 ± 1.1% at 37ºC for 4 h.

Animal Studies

Human Studies

[PubMed]

No publication is currently available.

References

1.

Ohki-Hamazaki H. , Iwabuchi M. , Maekawa F. Development and function of bombesin-like peptides and their receptors. Int J Dev Biol. 2005; 49 (2-3):293–300. [PubMed: 15906244]

2.

Rozengurt E. , Guha S. , Sinnett-Smith J. Gastrointestinal peptide signalling in health and disease. Eur J Surg Suppl. 2002;(587):23–38. [PubMed: 16144198]

3.

Roesler R. , Henriques J.A. , Schwartsmann G. Gastrin-releasing peptide receptor as a molecular target for psychiatric and neurological disorders. CNS Neurol Disord Drug Targets. 2006; 5 (2):197–204. [PubMed: 16611092]

4.

Maina T. , Nock B. , Mather S. Targeting prostate cancer with radiolabelled bombesins. Cancer Imaging. 2006; 6 :153–7. [PMC free article: PMC1693771] [PubMed: 17098646]

5.

Smith C.J. , Volkert W.A. , Hoffman T.J. Radiolabeled peptide conjugates for targeting of the bombesin receptor superfamily subtypes. Nucl Med Biol. 2005; 32 (7):733–40. [PubMed: 16243649]

6.

Weiner R.E. , Thakur M.L. Radiolabeled peptides in oncology: role in diagnosis and treatment. BioDrugs. 2005; 19 (3):145–63. [PubMed: 15984900]

7.

Zhou J. , Chen J. , Mokotoff M. , Ball E.D. Targeting gastrin-releasing peptide receptors for cancer treatment. Anticancer Drugs. 2004; 15 (10):921–7. [PubMed: 15514561]

8.

Durkan K. , Lambrecht F.Y. , Unak P. Radiolabeling of bombesin-like peptide with 99mTc: 99mTc-litorin and biodistribution in rats. Bioconjug Chem. 2007; 18 (5):1516–20. [PubMed: 17760415]