⁶⁶Ga-PET-imaging of GRPR-expression in prostate cancer: production and characterization of [⁶⁶Ga]Ga-NOTA-PEG₂-RM26

Molecular imaging of the gastrin-releasing peptide receptor (GRPR) could improve patient management in prostate cancer. This study aimed to produce gallium-66 (T_½ = 9.5 h) suitable for radiolabeling, and investigate the imaging properties of gallium-66 labeled GRPR-antagonist NOTA-PEG₂-RM26 for later-time point PET-imaging of GRPR expression. Gallium-66 was cyclotron-produced using a liquid target, and enriched [⁶⁶Zn]Zn(NO₃)₂. In vitro, [⁶⁶Ga]Ga-NOTA-PEG₂-RM26 was characterized in GRPR-expressing PC-3 prostate cancer cells. In vivo, specificity test and biodistribution studies were performed 3 h and 22 h pi in PC-3 xenografted mice. microPET/MR was performed 3 h and 22 h pi. Biodistribution of [⁶⁶Ga]Ga-NOTA-PEG₂-RM26 was compared with [⁶⁸Ga]Ga-NOTA-PEG₂-RM26 3 h pi. [⁶⁶Ga]Ga-NOTA-PEG₂-RM26 was successfully prepared with preserved binding specificity and high affinity towards GRPR. [⁶⁶Ga]Ga-NOTA-PEG₂-RM26 cleared rapidly from blood via kidneys. Tumor uptake was GRPR-specific and exceeded normal organ uptake. Normal tissue clearance was limited, resulting in no improvement of tumor-to-organ ratios with time. Tumors could be clearly visualized using microPET/MR. Gallium-66 was successfully produced and [⁶⁶Ga]Ga-NOTA-PEG₂-RM26 was able to clearly visualize GRPR-expression both shortly after injection and on the next day using PET. However, delayed imaging did not improve contrast for Ga-labeled NOTA-PEG₂-RM26.