64Cu labeled ambasar-RGD2 for micro-PET imaging of integrin αvβ3expression

Hancheng Cai, Zibo Li, Chiun Wei Huang, Ryan Park, Peter S. Conti

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Integrin αvβ3plays a critical role in tumor-induced angiogenesis and metastasis. Previously, a 64Cu-AmBaSar-RGD monomer with high in vivo stability compared with 64Cu-DOTA-RGD was developed for integrin αvβ33 PET imaging. It has been established that dimeric RGD peptides have higher receptor-binding affinity and superior in vivo kinetics compared with monomeric RGD peptides due to the polyvalency effect. In this context, we synthesized and evaluated 64Cu-labeled AmBaSar dimeric RGD conjugates (64Cu-AmBaSar-RGD2) for PET imaging of integrin αvβ3 expression.The dimeric RGD peptide was conjugated with a cage-like chelator AmBaSar and labeled with 64Cu. Cell binding, microPET imaging, receptor blocking, and biodistribution studies of 64Cu-AmBaSar-RGD2 were conducted in the U87MG human glioblastoma xenograft model. AmBaSar-RGD2 conjugate was obtained in reasonable yield (45.0 ± 2.5%, n= 4)and the identity was confirmed by HPLC and MS (found 1779.8, calculated m/z for [M+H]+ M: C81H125N27O19 1779.9).64Cu-AmBaSar-RGD2 was obtained with high radiochemical yield (92.0 ± 1.3%) and purity (≥98.0%) under mild conditions(pH 5.0~5.5, 23~37 °C) in 30 min. The specific activity of 64Cu-AmBaSar-RGD2 was estimated to be 15-22GBq/μmol at the end of synthesis. Based on microPET imaging and biodistribution studies, 64Cu-AmBaSar-RGD2 has demonstrated higher tumor uptake at selected time points than 64Cu-AmBaSar-RGD. At 20 h p.i., the tumor uptake reached 0.65 ± 0.05 %ID/g for 64Cu-AmBaSar-RGD and 1.76 ± 0.38 %ID/g for 64Cu-AmBaSar-RGD2, respectively. The integrin αvβ3 targeting specificity was confirmed by blocking experiments. Therefore, the new tracer 64Cu-AmBaSar-RGD2 exhibited better tumor-targeting efficacy and more favorable in vivo pharmacokinetics than the 64Cu labeled RGD monomer due to the polyvalency effect.

Original languageEnglish (US)
Pages (from-to)68-74
Number of pages7
JournalCurrent Radiopharmaceuticals
Volume4
Issue number1
StatePublished - Jun 2011

Fingerprint

Integrins
Neoplasms
Glioblastoma
Chelating Agents
Heterografts
64Cu-AmBaSar-RGD2
Pharmacokinetics
High Pressure Liquid Chromatography
Neoplasm Metastasis
arginyl-glycyl-aspartic acid

Keywords

  • Bifunctional chelator
  • Copper-64
  • Integrin αβ
  • PET
  • RGD

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging
  • Pharmacology

Cite this

Cai, H., Li, Z., Huang, C. W., Park, R., & Conti, P. S. (2011). 64Cu labeled ambasar-RGD2 for micro-PET imaging of integrin αvβ3expression. Current Radiopharmaceuticals, 4(1), 68-74.

64Cu labeled ambasar-RGD2 for micro-PET imaging of integrin αvβ3expression. / Cai, Hancheng; Li, Zibo; Huang, Chiun Wei; Park, Ryan; Conti, Peter S.

In: Current Radiopharmaceuticals, Vol. 4, No. 1, 06.2011, p. 68-74.

Research output: Contribution to journalArticle

Cai, H, Li, Z, Huang, CW, Park, R & Conti, PS 2011, '64Cu labeled ambasar-RGD2 for micro-PET imaging of integrin αvβ3expression', Current Radiopharmaceuticals, vol. 4, no. 1, pp. 68-74.
Cai, Hancheng ; Li, Zibo ; Huang, Chiun Wei ; Park, Ryan ; Conti, Peter S. / 64Cu labeled ambasar-RGD2 for micro-PET imaging of integrin αvβ3expression. In: Current Radiopharmaceuticals. 2011 ; Vol. 4, No. 1. pp. 68-74.
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abstract = "Integrin αvβ3plays a critical role in tumor-induced angiogenesis and metastasis. Previously, a 64Cu-AmBaSar-RGD monomer with high in vivo stability compared with 64Cu-DOTA-RGD was developed for integrin αvβ33 PET imaging. It has been established that dimeric RGD peptides have higher receptor-binding affinity and superior in vivo kinetics compared with monomeric RGD peptides due to the polyvalency effect. In this context, we synthesized and evaluated 64Cu-labeled AmBaSar dimeric RGD conjugates (64Cu-AmBaSar-RGD2) for PET imaging of integrin αvβ3 expression.The dimeric RGD peptide was conjugated with a cage-like chelator AmBaSar and labeled with 64Cu. Cell binding, microPET imaging, receptor blocking, and biodistribution studies of 64Cu-AmBaSar-RGD2 were conducted in the U87MG human glioblastoma xenograft model. AmBaSar-RGD2 conjugate was obtained in reasonable yield (45.0 ± 2.5{\%}, n= 4)and the identity was confirmed by HPLC and MS (found 1779.8, calculated m/z for [M+H]+ M: C81H125N27O19 1779.9).64Cu-AmBaSar-RGD2 was obtained with high radiochemical yield (92.0 ± 1.3{\%}) and purity (≥98.0{\%}) under mild conditions(pH 5.0~5.5, 23~37 °C) in 30 min. The specific activity of 64Cu-AmBaSar-RGD2 was estimated to be 15-22GBq/μmol at the end of synthesis. Based on microPET imaging and biodistribution studies, 64Cu-AmBaSar-RGD2 has demonstrated higher tumor uptake at selected time points than 64Cu-AmBaSar-RGD. At 20 h p.i., the tumor uptake reached 0.65 ± 0.05 {\%}ID/g for 64Cu-AmBaSar-RGD and 1.76 ± 0.38 {\%}ID/g for 64Cu-AmBaSar-RGD2, respectively. The integrin αvβ3 targeting specificity was confirmed by blocking experiments. Therefore, the new tracer 64Cu-AmBaSar-RGD2 exhibited better tumor-targeting efficacy and more favorable in vivo pharmacokinetics than the 64Cu labeled RGD monomer due to the polyvalency effect.",
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