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Efficient Construction of PET/fluorescence Probe Based on Sarcophagine Cage: An Opportunity to Integrate Diagnosis With Treatment

Efficient Construction of PET/fluorescence Probe Based on Sarcophagine Cage: An Opportunity to Integrate Diagnosis With Treatment

Shuanglong Liu, Dan Li, Chiun-Wei Huang, Li-Peng Yap, Ryan Park, Hong Shan, Zibo Li, Peter S Conti

Mol Imaging Biol. 2012 Dec;14(6):718-24.

PMID: 22476968

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP1188292547	Alkyne cyanine dye 718		1188292-54-7	Price

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