title: Efficient construction of PET/fluorescence probe based on sarcophagine cage: an opportunity to integrate diagnosis with treatment.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.affiliation: Department of Radiology, Keck School of Medicine, Molecular Imaging Center, University of Southern California, Los Angeles, CA 90033, USA.
authors.forename: Shuanglong
authors.initials: S
authors.lastname: Liu
authors.forename: Dan
authors.initials: D
authors.lastname: Li
authors.forename: Chiun-Wei
authors.initials: CW
authors.lastname: Huang
authors.forename: Li-Peng
authors.initials: LP
authors.lastname: Yap
authors.forename: Ryan
authors.initials: R
authors.lastname: Park
authors.forename: Hong
authors.initials: H
authors.lastname: Shan
authors.forename: Zibo
authors.initials: Z
authors.lastname: Li
authors.forename: Peter S
authors.initials: PS
authors.lastname: Conti
mesh_terms: D000818:Animals; D002232:Carbocyanines / Q000138:chemical synthesis / Q000737:chemistry; D045744:Cell Line, Tumor; D002614:Chelating Agents / Q000138:chemical synthesis / Q000737:chemistry; D004151:Dipeptides / Q000138:chemical synthesis* / Q000737:chemistry; D005260:Female; D005453:Fluorescence; D005456:Fluorescent Dyes / Q000138:chemical synthesis* / Q000737:chemistry; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry; D009928:Organ Specificity; D049268:Positron-Emission Tomography / Q000379:methods*; D023041:Xenograft Model Antitumor Assays
chemical_list: C098793:CY5.5 cyanine dye; D002232:Carbocyanines; D002614:Chelating Agents; D004151:Dipeptides; D005456:Fluorescent Dyes; D009842:Oligopeptides; C016968:alanyltyrosine; C047981:arginyl-glycyl-aspartic acid