18F-Labeled BBN-RGD Heterodimer for Prostate Cancer Imaging

Journal of Nuclear Medicine

Eun Kyoung Ryu¹  Zi-Bo Li¹  Zhanhong Wu¹  Xiaoyuan Chen¹  Kai Chen¹ 

[1] Molecular Imaging Program at Stanford (MIPS), Department of Radiology, Biophysics, and Bio-X Program, Stanford University School of Medicine, Stanford, California Molecular Imaging Program at Stanford (MIPS), Department of Radiology, Biophysics, and Bio-X Program, Stanford University School of Medicine, Stanford, California Molecular Imaging Program at Stanford (MIPS), Department of Radiology, Biophysics, and Bio-X Program, Stanford University School of Medicine, Stanford, California

关键词: integrin α_vβ₃;    gastrin-releasing peptide receptor;    BBN-RGD heterodimer;    PET;    ¹⁸F;   

DOI  :  10.2967/jnumed.107.048009

学科分类：医学（综合）

来源: Society of Nuclear Medicine

【 摘 要 】

Both bombesin (BBN) analogs and cyclic RGD peptides have been suitably radiolabeled for prostate cancer imaging. However, the limited expression of gastrin-releasing peptide receptor (GRPR) and integrin αvβ3 as well as unfavorable in vivo kinetics limited further applications of these imaging agents. We hypothesize that a peptide ligand recognizing both GRPR and integrin will be advantageous because of its dual-receptor–targeting ability. Methods: A BBN-RGD heterodimer was synthesized from bombesin(7–14) and c(RGDyK) through a glutamate linker and then labeled with 18F via the N-succinimidyl-4-18F-fluorobenzoate (18F-SFB) prosthetic group. The receptor-binding characteristics and tumor-targeting efficacy of 18F-FB-BBN-RGD were tested in vitro and in vivo. Results: FB-BBN-RGD had comparable integrin αvβ3-binding affinity with c(RGDyK) and comparable GRPR-binding affinity with BBN(7–14). 18F-FB-BBN-RGD had significantly higher tumor uptake compared with monomeric RGD and monomeric BBN peptide tracer analogs at all time points examined. The PC-3 tumor uptake of 18F-FB-BBN-RGD was inhibited only partially in the presence of an excess amount of unlabeled BBN(7–14) or c(RGDyK) but was blocked completely in the presence of both BBN(7–14) and c(RGDyK). Compared with 18F-FB-BBN and 18F-FB-RGD, 18F-FB-BBN-RGD also had improved pharmacokinetics, resulting in a significantly higher imaging quality. Conclusion: Dual integrin αvβ3 and GRPR recognition showed significantly improved tumor-targeting efficacy and pharmacokinetics compared with 18F-labeled RGD and BBN analogs. The same heterodimeric ligand design may also be applicable to other receptor system combinations and other imaging modalities.

【 授权许可】

Unknown