18F-Labeled Bombesin Analog for Specific and Effective Targeting of Prostate Tumors Expressing Gastrin-Releasing Peptide Receptors

Journal of Nuclear Medicine

Linjing Mu¹  Cindy R. Fischer¹  Michael Honer¹  Ludger Dinkelborg¹  Sandra Borkowski¹  Simon M. Ametamey¹  Ananth Srinivasan¹  Pius A. Schubiger¹  Miljen Martic¹  Timo Stellfeld¹  Keith Graham¹  Lutz Lehmann¹ 

关键词: bombesin;    GRPr;    PC-3;    LNCaP;    PET;    choline;   

DOI  :  10.2967/jnumed.110.081620

学科分类：医学（综合）

来源: Society of Nuclear Medicine

【 摘 要 】

Bombesin is a peptide exhibiting high affinity for the gastrin-releasing peptide receptor (GRPr), which is highly overexpressed on prostate cancer cells. In the present study, we developed an 18F-labeled bombesin analog, 18F-BAY 86-4367, which is currently being clinically tested for use in PET of prostate cancer. Methods: In vitro pharmacologic studies were performed to characterize the nonradioactive (19F) standard of the bombesin analog for binding affinity and selectivity for GRPr. The stability of 18F-BAY 86-4367 was determined in murine and human plasma. In vivo, the tumor-targeting potential and pharmacokinetic profile of the 18F tracer were analyzed with biodistribution experiments and PET studies of prostate tumor–bearing mice. Results: The nonradioactive (19F) standard of the bombesin analog showed subnanomolar and GRPr-selective binding affinity. The stability of the tracer in murine and human plasma was found to be high. In 2 prostate cancer xenograft models (PC-3 and LNCaP), 18F-BAY 86-4367 showed more specific and effective GRPr-based targeting in vivo than the benchmark radiotracers 18F-fluoroethylcholine and 18F-FDG. In addition, rapid tumor targeting and fast renal excretion (∼70%) and hepatobiliary excretion (∼10%) were identified in both xenograft models. Furthermore, PET studies provided clear and specific visualization of PC-3 tumors in mice. Conclusion: Favorable preclinical data showing specific and effective tumor targeting by 18F-BAY 86-4367 suggest that a clinical trial be undertaken to test its diagnostic utility in PET for prostate carcinoma patients.

【 授权许可】

Unknown