Evaluation of copper-64 labeled AmBaSar conjugated cyclic RGD peptide for improved MicroPET imaging of integrin αvβ3 expression

Hancheng Cai, Zibo Li, Chiun Wei Huang, Anthony H. Shahinian, Hui Wang, Ryan Park, Peter S. Conti

Research output: Contribution to journalArticlepeer-review

65 Scopus citations


Recently, we have developed a new cage-like bifunctional chelator 4-((8-amino-3,6,10,13,16,19-hexaazabicyclo [6.6.6] icosane-1-ylamino) methyl) benzoic acid (AmBaSar) for copper-64 labeling and synthesized the positron emission tomography (PET) tracer 64Cu-AmBaSar-RGD. In this study, we further evaluate the biological property of this new AmBaSar chelator by using 64Cu-AmBaSar-RGD as the model compound. In vitro and in vivo stability, lipophilicity, cell binding and uptake, microPET imaging, receptor blocking experiments, and biodistribution studies of 64Cu-AmBaSar-RGD were investigated, and the results were directly compared with the established radiotracer 64Cu-DOTA-RGD. The 64Cu-AmBaSar-RGD was obtained with high radiochemical yield (≥95%) and purity (≥99%) under mild conditions (pH 5.0-5.5 and 23-37 °C) in less than 30 min. For in vitro studies, the radiochemical purity of 64Cu-AmBaSar-RGD was more than 97% in PBS or FBS and 95% in mouse serum after 24 h of incubation. The log P value of 64Cu-AmBaSar-RGD was-2.44 ± 0.12. For in vivo studies, 64Cu-AmBaSar-RGD and 64Cu-DOTA-RGD have demonstrated comparable tumor uptake at selected time points on the basis of microPET imaging. The integrin αvβ3 receptor specificity was confirmed by blocking experiments for both tracers. Compared with 64Cu-DOTA-RGD, 64Cu-AmBaSar-RGD demonstrated much lower liver accumulation in both microPET imaging and biodistribution studies. Metabolic studies also directly supported the observation that 64Cu-AmBaSar-RGD was more stable in vivo than 64Cu-DOTA- RGD. In summary, the in vitro and in vivo evaluations of the 64Cu-AmBaSar-RGD have demonstrated its improved Cu-chelation stability compared with that of the established tracer 64Cu-DOTA-RGD. The AmBaSar chelator will also have general applications for 64Cu labeling of various bioactive molecules in high radiochemical yield and high in vivo stability.

Original languageEnglish (US)
Pages (from-to)1417-1424
Number of pages8
JournalBioconjugate Chemistry
Issue number8
StatePublished - Aug 18 2010

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Biomedical Engineering
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry


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