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

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

Correspondence: For correspondence or reprints contact: Xiaoyuan Chen, PhD, Molecular Imaging Program at Stanford (MIPS), Department of Radiology, Biophysics, and Bio-X Program, Stanford University School of Medicine, 1201 Welch Rd., P095, Stanford, CA 94305-5484. E-mail: shawchen{at}stanford.edu

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 _vβ₃ 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 _vβ₃-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 _vβ₃ 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.

Key Words: integrin _vβ₃ • gastrin-releasing peptide receptor • BBN-RGD heterodimer • PET • ¹⁸F

COPYRIGHT © 2008 by the Society of Nuclear Medicine, Inc.

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				H. L. Goel, J. Li, S. Kogan, and L. R Languino Integrins in prostate cancer progression Endocr. Relat. Cancer, September 1, 2008; 15(3): 657 - 664. [Abstract] [Full Text] [PDF]