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-1/2=9.5 h) suitable for radiolabeling, and investigate the imaging properties of gallium-66 labeled GRPR-antagonist NOTA-PEG(2)-RM26 for later-time point PET-imaging of GRPR expression. Gallium-66 was cyclotron-produced using a liquid target, and enriched [Zn-66]Zn(NO3)(2). In vitro, [Ga-66]Ga-NOTA-PEG(2)-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 [Ga-66]Ga-NOTA-PEG(2)-RM26 was compared with [Ga-68]Ga-NOTA-PEG(2)-RM26 3 h pi. [Ga-66]Ga-NOTA-PEG(2)-RM26 was successfully prepared with preserved binding specificity and high affinity towards GRPR. [Ga-66]Ga-NOTA-PEG(2)-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 [Ga-66]Ga-NOTA-PEG(2)-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-PEG(2)-RM26.

Automated summary

This study successfully produced gallium-66 for radiolabeling and investigated the imaging properties of gallium-66 labeled GRPR-antagonist for PET imaging of GRPR expression. The results demonstrated that the radiotracer could clearly visualize GRPR expression, but delayed imaging did not improve contrast.