In vitro and in vivo analysis of [(64)Cu-NO2A-8-Aoc-BBN(7-14)NH(2)]: a site-directed radiopharmaceutical for positron-emission tomography imaging of T-47D human breast cancer tumors.
Nucl Med Biol
; 36(2): 171-81, 2009 Feb.
Article
em En
| MEDLINE
| ID: mdl-19217529
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Compostos Organometálicos
/
Neoplasias da Mama
/
Bombesina
/
Radioisótopos de Cobre
/
Receptores da Bombesina
/
Compostos Radiofarmacêuticos
/
Tomografia por Emissão de Pósitrons
Tipo de estudo:
Guideline
Limite:
Animals
/
Female
/
Humans
Idioma:
En
Revista:
Nucl Med Biol
Assunto da revista:
BIOLOGIA
/
MEDICINA NUCLEAR
Ano de publicação:
2009
Tipo de documento:
Article
País de afiliação:
Estados Unidos