Efficient construction of PET/fluorescence probe based on sarcophagine cage: an opportunity to integrate diagnosis with treatment.

Abstract

PURPOSE:

Due to the shortage of established platforms/methods for multimodality probe construction, in this study, we developed a heterofunctional chelator, BaAn(Boc)Sar, from sarcophagine cage as a general platform for dual-modality probe construction.

PROCEDURES:

A dual-modality probe for positron-emission tomography (PET) and fluorescence imaging was synthesized using the developed BaAn(Boc)Sar chelator. The c(RGDyK)(2) peptide (denoted as RGD(2)) and fluorescence dye Cy5.5 were conjugated with BaAn(Boc)Sar to form BaAnSar-RGD(2)-Cy5.5. Then, BaAnSar-RGD(2)-Cy5.5 was labeled with (64)Cu in ammonium acetate buffer. PET and fluorescent imaging were carried out to evaluate (64)Cu-BaAnSar-RGD(2)-Cy5.5 in nude mice bearing U87MG glioblastoma xenograft.

RESULTS:

The BaAnSar-RGD(2)-Cy5.5 was labeled with (64)Cu very efficiently in 0.1 M NH(4)OAc buffer within 10 min at 37 °C in the yield of 86.7 ± 4.4 % (n = 3). The specific activity of (64)Cu-BaBaSar-RGD(2) was controlled at 50-200 mCi/μmol for the consideration of both PET and optical imaging. MicroPET quantification analysis shows that the U87MG tumor uptake is 6.41 ± 0.28, 6.51 ± 1.45, and 5.92 ± 1.57 %ID/g at 1, 4, and 20 h postinjection, respectively. Good correlation was obtained between the tumor to muscle ratios measured by the radioactivity and fluorescence intensity. As a proof of concept, an animal surgery study demonstrated that this dual-modality probe would greatly benefit the patients because the PET moiety could be used for tumor detection, and the fluorescent moiety would allow image-guided surgery.

CONCLUSIONS:

Our findings demonstrated the effectiveness and feasibility of preparing dual-modality imaging probes based on the sarcophagine scaffold. The resulting PET and fluorescent imaging probe also holds a great potential for clinical translation.

• Authors: Shuanglong Liu, Dan Li, Chiun-Wei Huang, Li-Peng Yap, Ryan Park, Hong Shan, Zibo Li, Peter S Conti
• Journal: Molecular imaging and biology (Mol Imaging Biol) Vol. 14 Issue 6 Pg. 718-24 (Dec 2012) ISSN: 1860-2002 [Electronic] United States
• PMID: 22476968 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• CY5.5 cyanine dye
• Carbocyanines
• Chelating Agents
• Dipeptides
• Fluorescent Dyes
• Oligopeptides
• alanyltyrosine
• arginyl-glycyl-aspartic acid

Topics

• Animals
• Carbocyanines (chemical synthesis, chemistry)
• Cell Line, Tumor
• Chelating Agents (chemical synthesis, chemistry)
• Dipeptides (chemical synthesis, chemistry)
• Female
• Fluorescence
• Fluorescent Dyes (chemical synthesis, chemistry)
• Humans
• Mice
• Mice, Nude
• Oligopeptides (chemical synthesis, chemistry)
• Organ Specificity
• Positron-Emission Tomography (methods)
• Xenograft Model Antitumor Assays