Department of Nuclear Medicine, University Hospital Freiburg, Freiburg, Germany.
J Nucl Med. 2011 Aug;52(8):1276-84. doi: 10.2967/jnumed.111.087700. Epub 2011 Jul 15.
PET with (18)F-labeled arginine-glycine-aspartic acid (RGD) peptides can visualize and quantify α(ν)β(3) integrin expression in patients, but radiolabeling is complex and image contrast is limited in some tumor types. The development of (68)Ga-RGD peptides would be of great utility given the convenience of (68)Ga production and radiolabeling, and (64)Cu-RGD peptides allow for delayed imaging with potentially improved tumor-to-background ratios.
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 (68)Ga or (64)Cu. 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.
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 (18)F-labeled RGD peptides. At 18 h after injection, however, (64)Cu-NODAGA-c(RGDfK) and (64)Cu-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.
The ease of radiolabeling makes (68)Ga-NODAGA-c(RGDfK) an attractive alternative to (18)F-labeled RGD peptides. The high tumor-to-background ratios of (64)Cu-NODAGA-c(RGDfK) and (64)Cu-CB-TE2A-c(RGDfK) at 18 h warrant testing of (64)Cu-labeled RGD peptides in patients.
使用螯合剂 DOTA、1,4,7-三氮杂环壬烷、1-谷氨酸-4,7-乙酸（NODAGA）和 4,11-双（羧甲基）-1,4,8,11-四氮杂环[6.6.2]十六烷（CB-TE2A）标记环状五肽 c（RGDfK）与（68）Ga 或（64）Cu。室温下，两种放射性核素在 10 分钟内即可完成 NODAGA-c（RGDfK）的标记。对于其他偶联物，可以在 95°C 下孵育长达 30 分钟。通过基于细胞的受体结合测定评估金属肽的亲和力谱。在携带皮下 U87MG 胶质母细胞瘤异种移植的裸鼠中进行小动物 PET 研究和生物分布研究。
放射性标记的简便性使得（68）Ga-NODAGA-c（RGDfK）成为（18）F 标记 RGD 肽的有吸引力的替代品。（64）Cu-NODAGA-c（RGDfK）和（64）Cu-CB-TE2A-c（RGDfK）在 18 小时时具有高达 20 倍的肿瘤与器官比值，这一比值很高，值得在患者中测试（64）Cu 标记的 RGD 肽。
