In vitro and in vivo analysis of [64Cu-NO2A-8-Aoc-BBN(7–14)NH2]: a site-directed radiopharmaceutical for positron-emission tomography imaging of T-47D human breast cancer tumors

Abstract

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

177Lu-Dendrimer Conjugated to Folate and Bombesin with Gold Nanoparticles in the Dendritic Cavity: A Potential Theranostic Radiopharmaceutical

“…Clinical studies 2 Journal of Nanomaterials in women using radio-bombesin derivatives have shown successful radionuclide imaging of breast tumors [7][8][9][10]. In particular, the GRPR is highly expressed in T47D human breast cells, and that is the reason why these cells have been used as tumor models to evaluate new bombesin probes [6,[11][12][13].…”

Molecular Imaging of Breast Cancer Tissue via Site-Directed Radiopharmaceuticals

“…This implies that occupation of this non-chelating carboxylate of NOTA, as in our bifunctional NO2A, may not alter the native structure of the Cu-NOTA complex. We have recently evaluated 64 Cu-NO2A-8-Aoc-BBN(7-14)NH 2 radiopharmaceutical ( Figure 4) to be used as a PET targeting agent for primary or metastatic breast cancer disease (Prasanphanich et al, 2009). In this study, we were able to prepare high specific activity 64 Cu-NO2A-8-Aoc-BBN(7-14)NH 2 conjugate in very high radiochemical yield and to evaluate the 1) targeting capacity of 64 Cu-NO2A-8-Aoc-BBN(7-14)NH 2 for GRPr-positive tissues in vivo; 2 ) p a r t i c u l a r r o u t e s o f c l e a r a n c e ; a n d 3 ) e x t e n t o f r e t e n t i o n o f radiopharmaceutical in radiosensitive tissues.…”

The Gastrin-Releasing Peptide Receptor as a Marker of Dysplastic Alterations in Cervical Epithelial Cells

“…These data provided the molecular basis for exploiting GRPR as a target for cervical cancer diagnosis. GRPR is already being studied for diagnostic purposes in other types of cancer, like breast and prostate cancer, with promising results [14,15,16,17]. However, to date no studies have evaluated GRPR expression in cancer using immunocytochemistry.…”