Preclinical Evaluation of Tc-Labeled GRPR Antagonists maSSS/SES-PEG-RM26 for Imaging of Prostate Cancer.

BACKGROUND

Gastrin-releasing peptide receptor (GRPR) is an important target for imaging of prostate cancer. The wide availability of single-photon emission computed tomography/computed tomography (SPECT/CT) and the generator-produced Tc can be utilized to facilitate the use of GRPR-targeting radiotracers for diagnostics of prostate cancers.

METHODS

Synthetically produced mercaptoacetyl-Ser-Ser-Ser (maSSS)-PEG-RM26 and mercaptoacetyl-Ser-Glu-Ser (maSES)-PEG-RM26 (RM26 = d-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH) were radiolabeled with Tc and characterized in vitro using PC-3 cells and in vivo, using NMRI or PC-3 tumor bearing mice. SPECT/CT imaging and dosimetry calculations were performed for [Tc]Tc-maSSS-PEG-RM26.

RESULTS

Peptides were radiolabeled with high yields (>98%), demonstrating GRPR specific binding and slow internalization in PC-3 cells. [Tc]Tc-maSSS-PEG-RM26 outperformed [Tc]Tc-maSES-PEGRM26 in terms of GRPR affinity, with a lower dissociation constant (61 pM vs 849 pM) and demonstrating higher tumor uptake. [Tc]Tc-maSSS-PEG-RM26 had tumor-to-blood, tumor-to-muscle, and tumor-to-bone ratios of 97 ± 56, 188 ± 32, and 177 ± 79, respectively. SPECT/CT images of [Tc]Tc-maSSS-PEG-RM26 clearly visualized the GRPR-overexpressing tumors. The dosimetry estimated for [Tc]Tc-maSSS-PEG-RM26 showed the highest absorbed dose in the small intestine (1.65 × 10 mGy/MBq), and the effective dose is 3.49 × 10 mSv/MBq.

CONCLUSION

The GRPR antagonist maSSS-PEG-RM26 is a promising GRPR-targeting agent that can be radiolabeled through a single-step with the generator-produced Tc and used for imaging of GRPR-expressing prostate cancer.