No abstract

Reactions of Re V , tetradentate Schiff base complexes with tertiary phosphines have previously yielded both rearranged Re V and reduced Re III complexes. To further understand this chemistry, the rigid diiminediphenol (N 2 O 2 ) Schiff base ligand sal 2 phen (N,N'-ophenylenebis(salicylaldimine)) was reacted with (n-Bu 4 N) [ReOCl 4 ] to yield trans-[ReOCl(sal 2 phen)] (1). On reaction with triphenylphosphine (PPh 3 ), a rearranged Re V product cis-[ReO(PPh 3 )(sal 2 phen*)]PF 6 (2), in which one of the imines was reduced to an amine during the reaction, and the reduced Re III products trans-[ReCl(PPh 3 )(sal 2 phen)] (4) and trans-[Re(PPh 3 ) 2 (sal 2 phen)] + (5) were isolated. Reaction of sal 2 phen with [ReCl 3 (PPh 3 ) 2 (CH 3 CN)] resulted in the isolation of [ReCl 2 (PPh 3 ) 2 (salphen)] (3). The compounds were characterized using standard spectroscopic methods, elemental analyses and single crystal X-ray crystallography.

Introduction-Human breast cancer, from which the T-47D cell line was derived, is known to overexpress the gastrin-releasing peptide receptor (GRPR) in some cases. Bombesin (BBN), an agonist for the GRPR, has been appended with a radionuclide capable of positron-emission tomography (PET) imaging and therapy. 64 Cu-NO2A-8-Aoc-BBN(7-14)NH 2 (NO2A=1,4,7-triazacyclononane-1,4-diacetate) has produced high-quality microPET images of GRPR-positive breast cancer xenografted tumors in mice.Methods-The imaging probe was synthesized by solid-phase peptide synthesis followed by manual conjugation of the 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) bifunctional chelator and radiolabeling in aqueous solution. The radiolabeled conjugate was subjected to in vitro and in vivo studies to determine its specificity for the GRPR and its pharmacokinetic profile. A T-47D tumor-bearing mouse was imaged with microPET/CT and microMRI imaging.Results-The 64 Cu-NO2A-8-Aoc-BBN(7-14)NH 2 targeting vector was determined to specifically localize in GRPR-positive tissue. Accumulation was observed in the tumor in sufficient quantities to allow for identification of tumors in microPET imaging procedures. For example, uptake and retention in T-47D xenografts at 1, 4 and 24 h were determined to be 2.27±0.08, 1.35±0.14 and 0.28 ±0.07 % ID/g, respectively. Conclusions-The 64 Cu-NO2A-8-Aoc-BBN(7-14)NH 2 produced high-quality microPET images. The pharmacokinetic profile justifies investigation of this bioconjugate as a potentially useful diagnostic/therapeutic agent. Additionally, the bioconjugate would serve as a good starting point for modification and optimization of similar agents to maximize tumor uptake and minimize nontarget accumulation. NIH Public Access

[99mTc(CO)3-DTMA-(X)-BBN(7-14)NH2] conjugates displayed very high affinity for the gastrin releasing peptide receptor in vitro and in vivo. Therefore, these conjugates hold some propensity to be investigated as molecular imaging agents that specifically target human cancers uniquely expressing the gastrin releasing peptide receptor subtypes.