Novel 64Cu- and 68Ga-Labeled RGD Conjugates Show Improved PET Imaging of ανβ3 Integrin Expression and Facile Radiosynthesis

Journal of Nuclear Medicine

Friederike Deininger¹  Rebecca A. Dumont¹  Roland Haubner¹  Melpomeni Fani¹  Wolfgang A. Weber¹  Helmut R. Maecke¹ 

关键词: ⁶⁸Ga PET/CT;    ⁶⁴Cu PET/CT;    RGD conjugates;    angiogenesis;    integrins;   

DOI  :  10.2967/jnumed.111.087700

学科分类：医学（综合）

来源: Society of Nuclear Medicine

【 摘 要 】

PET with 18F-labeled arginine-glycine-aspartic acid (RGD) peptides can visualize and quantify ανβ3 integrin expression in patients, but radiolabeling is complex and image contrast is limited in some tumor types. The development of 68Ga-RGD peptides would be of great utility given the convenience of 68Ga production and radiolabeling, and 64Cu-RGD peptides allow for delayed imaging with potentially improved tumor-to-background ratios. Methods: We used the chelators DOTA,1,4,7-triazacyclononane,1-glutaric acid-4,7-acetic acid (NODAGA), and 4,11-bis(carboxymethyl)-1,4,8,11-tetraazabicyclo[6.6.2]hexadecane (CB-TE2A) to radiolabel the cyclic pentapeptide c(RGDfK) with 68Ga or 64Cu. NODAGA-c(RGDfK) was labeled at room temperature with both radionuclides within 10 min. Incubation at 95°C for up to 30 min was used for the other conjugates. The affinity profile of the metallopeptides was evaluated by a cell-based receptor-binding assay. Small-animal PET studies and biodistribution studies were performed in nude mice bearing subcutaneous U87MG glioblastoma xenografts. Results: The conjugates were labeled with a radiochemical purity greater than 97% and specific activities of 15–20 GBq/μmol. The affinity profile was similar for all metallopeptides and comparable to the reference standard c(RGDfV). In the biodistribution studies, all compounds demonstrated a relatively similar tumor and normal organ uptake at 1 h after injection that was comparable to published data on 18F-labeled RGD peptides. At 18 h after injection, however, 64Cu-NODAGA-c(RGDfK) and 64Cu-CB-TE2A-c(RGDfK) showed up to a 20-fold increase in tumor-to-organ ratios. PET studies demonstrated high-contrast images of the U87MG tumors at 18 h, confirming the biodistribution data. Conclusion: The ease of radiolabeling makes 68Ga-NODAGA-c(RGDfK) an attractive alternative to 18F-labeled RGD peptides. The high tumor-to-background ratios of 64Cu-NODAGA-c(RGDfK) and 64Cu-CB-TE2A-c(RGDfK) at 18 h warrant testing of 64Cu-labeled RGD peptides in patients.

【 授权许可】

Unknown