^99mTcNitrido(diphosphine)-Cys-β-Ala-Gln-Trp-Ala-Val-Gly-His-Leu-Met-NH₂

[^99mTcN(PNP6)-Cys-β-Ala-BBN(7-14)NH₂]

Background

[PubMed]

The amphibian bombesin (BBN or BN, a peptide of 14 amino acids) is an analog of human gastrin-releasing peptide (GRP, a peptide of 27 amino acids) that binds to GRP receptors (GRPR) with high affinity and specificity (1, 2). Both GRP and BBN share an amidated C-terminus sequence homology of seven amino acids, Trp-Ala-Val-Gly-His-Leu-Met-NH₂. BBN-Like peptides have been shown to induce various biological responses in diverse tissues, including the central nervous system (CNS) and the gastrointestinal (GI) system. They also act as potential growth factors for both normal and neoplastic tissues (3). Specific BBN receptors (BBN-R) have been identified on CNS and GI tissues and on a number of tumor cell lines (4). The BBN-R superfamily includes at least four different subtypes, namely neuromedin B (NMB or BB1), the GRPR subtype (BB2), the BB3 subtype, and the BB4 subtype. The findings of GRPR overexpression in various human tumors, such as breast, prostate, lung, colon, ovarian, and pancreatic cancers, provide opportunities for tumor imaging by designing specific molecular imaging agents to target the GRPR (5, 6).

Faintuch et al. (7) used ^99mTc-nitrido(diphosphine) for labeling Cys-β-Ala-Gln-Trp-Ala-Val-Gly-His-Leu-Met-NH₂ (Cys-BBN). ^99mTcNitrido(diphosphine)-Cys-BBN (^99mTcN(PNP6)-Cys-BBN) is being evaluated as a single-photon emission computed tomography (SPECT) imaging agent of GRPR in nude mice bearing PC-3 human prostate cancer cells.

Synthesis

[PubMed]

The ^99mTc-nitrido precursor species were prepared by the addition of succinic acid dihydrazide, nitrido-donor ligand, and stannous chloride to 0.5 ml aqueous Na^99mTcO₄ (7). The solution was incubated for 30 min at room temperature. After incubation, 0.045 mmol Cys-BBN and 3 µg diphosphine were added to the solution, which was then heated for 60 min at 100°C. ^99mTcN(PNP6)-Cys-BBN was purified with Sep-Pak with a radiochemical purity of >96% and a radiochemical yield of >97%. The specific activity of the purified product was not reported. The measured log P value was 0.98. ^99mTcN(PNP6)-Cys-BBN was >93% intact after 4 h in saline and in the presence of 100 mM cysteine.

In Vitro Studies: Testing in Cells and Tissues

[PubMed]

Faintuch et al. (7) performed in vitro internalization of ^99mTcN(PNP6)-Cys-BBN in cultured PC-3 cancer cells. PC-3 cells exhibited a rapid internalization with 8.9% of radioactivity accumulated at 30 min and 15.5% accumulated at 120 min after incubation.

Animal Studies

Human Studies

[PubMed]

No publication is currently available.