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J Nucl Med. 2008; 49 (Supplement 1):49P
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Oncology-Basic Science: Basic Science

Imaging - Peptides and Small Molecules

Radiolabeled BBN-RGD heterodimer for prostate cancer

Zibo Li1, Zhanhong Wu1, Kai Chen1, Eun-Kyoung Ryu1 and Xiaoyuan Chen1

1 Stanford University, Stanford, California


Formula

193

Objectives: Cyclic RGD peptides and bombesin (BBN) analogs have been radiolabeled for imaging integrin {alpha}vβ3 and gastrin-releasing peptide receptor (GRPR) expression in various cancer types. However, tracers derived from monomeric RGD and BBN suffer from relatively low tumor accumulation and retention as well as unfavorable in vivo kinetics. In this study we developed both 18F-labeled and 64Cu-labeled BBN-RGD heterodimer for positron emission tomography (PET) imaging of PC-3 tumor xenografted mice.

Methods: BBN-RGD hetero-dimer was synthesized from bombesin(7-14) and c(RGDyK) through a glutamate linker. BBN-RGD peptide was then labeled with 18F and 64Cu via 18F-SFB prosthetic group and DOTA chelating group respectively. The integrin and GRPR receptor binding characteristics of these heterodimeric peptide tracers were evaluated in vitro by cell binding assay and in vivo by quantitative microPET imaging studies.

Results: BBN-RGD based tracers had comparable {alpha}vβ3 integrin binding affinity with c(RGDyK) and comparable GRPR binding affinity with BBN(7-14). 18F-FB-BBN-RGD had significantly higher tumor uptake (3.8 ± 0.3%ID/g) compared with monomeric RGD (1.9 ± 0.2%ID/g) and bombesin (1.1 ± 0.2%ID/g) analogs at 1h. The receptor specificity of BBN-RGD based heterodimeric tracers were confirmed by effective blocking of the uptake in PC-3 tumor. Compared with their monomeric analogs, radio-labeled BBN-RGD had higher quality images.

Conclusions: Dual integrin {alpha}vβ3 and GRPR recognition showed significantly improved tumor targeting efficacy and pharmacokinetics compared with monomeric RGD and BBN analogs. The same heterodimeric ligand design may also be applicable to other receptor systems.

Research Support: National Cancer Institute: R01 CA119053, R21 CA121842, R21 CA102123, P50 CA114747, U54 CA119367, R24 CA93862; Department of Defense: W81XWH-07-1-0374, W81XWH-04-1-0697, W81XWH-06-1-0665, W81XWH-06-1-0042, DAMD17-03-1-0143





This Article
Services
Right arrow Email this article to a friend
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Right arrow Articles by Li, Z.
Right arrow Articles by Chen, X.
PubMed
Right arrow Articles by Li, Z.
Right arrow Articles by Chen, X.