Development of [64Cu]Cu-NODAGA-RGD-BBN as a Novel Radiotracer for Dual Integrin and GRPR-targeted Tumor PET Imaging.

Background: In this study, [64Cu]Cu-NODAGA-RGD-BBN was prepared and its preclinical assessments were evaluated for PET imaging of GRPR overexpressing tumors.

Methods: NODAGA-RGD-BBN heterodimer peptide was successfully labeled with cyclotronproduced copper-64 at optimized conditions. The radiochemical purity of the radiotracer was checked by HPLC and RTLC methods. The stability of the radiolabeled compound was assessed in PBS (4°C) and in human blood serum (37°C). Binding affinity and internalization of [64Cu]Cu-NODAGA-RGD-BBN were studied on PC3, LNCaP, and CHO cell lines. The biodistribution of the radiotracer was evaluated in normal and tumor-bearing mice.

Results: [64Cu]Cu-NODAGA-RGD-BBN was prepared with radiochemical purity >99 ± 0.7% (HPLC/ITLC) and specific activity of 18.5 ± 2.2 TBq/mmol. The radiotracer showed high stability in PBS (95 ± 1.05%) and in human blood serum (96 ± 1.24%) and, high affinity to the GRP expressing tumor cells. [64Cu]Cu-NODAGA-RGD-BBN showed hydrophilic (log p = -1.14) and agonistic nature. The biodistribution and imaging studies demonstrated high uptake at the tumor site at all intervals post-injection and 3-4 h post-injection can be considered an appropriate time of imaging.

Conclusion: The results indicated that [64Cu]Cu-NODAGA-RGD-BBN radiolabeled heterodimer peptide can be considered as a high-potential agent for PET imaging of GRPRoverexpressing tumors.