PT  - JOURNAL ARTICLE
AU  - Zi-Bo Li
AU  - Zhanhong Wu
AU  - Kai Chen
AU  - Eun Kyoung Ryu
AU  - Xiaoyuan Chen
TI  - <sup>18</sup>F-Labeled BBN-RGD Heterodimer for Prostate Cancer Imaging
AID  - 10.2967/jnumed.107.048009
DP  - 2008 Mar 01
TA  - Journal of Nuclear Medicine
PG  - 453--461
VI  - 49
IP  - 3
4099  - http://jnm.snmjournals.org/content/49/3/453.short
4100  - http://jnm.snmjournals.org/content/49/3/453.full
SO  - J Nucl Med2008 Mar 01; 49
AB  - 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.