Abstract | INTRODUCTION: 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.
|
Authors | Adam F Prasanphanich, Lauren Retzloff, Stephanie R Lane, Prasant K Nanda, Gary L Sieckman, Tammy L Rold, Lixin Ma, Said D Figueroa, Samantha V Sublett, Timothy J Hoffman, Charles J Smith |
Journal | Nuclear medicine and biology
(Nucl Med Biol)
Vol. 36
Issue 2
Pg. 171-81
(Feb 2009)
ISSN: 0969-8051 [Print] United States |
PMID | 19217529
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
|
Chemical References |
- (64)Cu-NO2A-8-Aoc-BBN(7-14)NH(2)
- Copper Radioisotopes
- Organometallic Compounds
- Radiopharmaceuticals
- Receptors, Bombesin
- Bombesin
|
Topics |
- Animals
- Bombesin
(metabolism)
- Breast Neoplasms
(diagnostic imaging)
- Cell Line, Tumor
- Copper Radioisotopes
- Female
- Humans
- Magnetic Resonance Imaging
- Mice
- Organometallic Compounds
- Positron-Emission Tomography
- Radiopharmaceuticals
(pharmacokinetics)
- Receptors, Bombesin
(analysis)
- Tissue Distribution
|