Novel Cu-64- and Ga-68-Labeled RGD Conjugates Show Improved PET Imaging of alpha(v)beta(3) Integrin Expression and Facile Radiosynthesis

作者：Dumont Rebecca A; Deininger Friederike; Haubner Roland; Maecke Helmut R; Weber Wolfgang A; Fani Melpomeni^*

来源：Journal of Nuclear Medicine, 2011, 52(8): 1276-1284.

DOI：10.2967/jnumed.111.087700

• Ga-68 PET/CT
• Cu-64 PET/CT
• RGD conjugates
• angiogenesis
• integrins

PET with F-18-labeled arginine-glycine-aspartic acid (RGD) peptides can visualize and quantify alpha(v)beta(3) integrin expression in patients, but radiolabeling is complex and image contrast is limited in some tumor types. The development of Ga-68-RGD peptides would be of great utility given the convenience of Ga-68 production and radiolabeling, and Cu-64-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 Ga-68 or Cu-64. NODAGA-c(RGDfK) was labeled at room temperature with both radionuclides within 10 min. Incubation at 95 degrees 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/mu mol. 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 F-18-labeled RGD peptides. At 18 h after injection, however, Cu-64-NODAGA-c(RGDfK) and Cu-64-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 Ga-68-NODAGA-c(RGDfK) an attractive alternative to F-18-labeled RGD peptides. The high tumor-to-background ratios of Cu-64-NODAGA-c(RGDfK) and Cu-64-CB-TE2A-c(RGDfK) at 18 h warrant testing of Cu-64-labeled RGD peptides in patients.

• 出版日期2011-8-1