Abstract
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 99mTc can be utilized to facilitate the use of GRPR-targeting radiotracers for diagnostics of prostate cancers. Methods: Synthetically produced mercaptoacetyl-Ser-Ser-Ser (maSSS)-PEG2-RM26 and mercaptoacetyl-Ser-Glu-Ser (maSES)-PEG2-RM26 (RM26 = d-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH2) were radiolabeled with 99mTc 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 [99mTc]Tc-maSSS-PEG2-RM26. Results: Peptides were radiolabeled with high yields (>98%), demonstrating GRPR specific binding and slow internalization in PC-3 cells. [99mTc]Tc-maSSS-PEG2-RM26 outperformed [99mTc]Tc-maSES-PEG2-RM26 in terms of GRPR affinity, with a lower dissociation constant (61 pM vs 849 pM) and demonstrating higher tumor uptake. [99mTc]Tc-maSSS-PEG2-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 [99mTc]Tc-maSSS-PEG2-RM26 clearly visualized the GRPR-overexpressing tumors. The dosimetry estimated for [99mTc]Tc-maSSS-PEG2-RM26 showed the highest absorbed dose in the small intestine (1.65 × 10−3 mGy/MBq), and the effective dose is 3.49 × 10−3 mSv/MBq. Conclusion: The GRPR antagonist maSSS-PEG2-RM26 is a promising GRPR-targeting agent that can be radiolabeled through a single-step with the generator-produced 99mTc and used for imaging of GRPR-expressing prostate cancer.
Highlights
The radiolabeled Gastrin-releasing peptide receptor (GRPR) antagonist [68 Ga]Ga-NOTA-PEG3 -RM26 performed better than an agonist [68 Ga]Ga-BBN when compared in a clinical study [19]
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The main aim of99m this study was study was to provide a radiotracer that will be simple to radiolabel with Tc and to use to provide a radiotracer that will be simple to radiolabel with 99m Tc and to use in clinics for in clinics for imaging GRPR-overexpressing prostate cancers
Summary
The radiolabeled GRPR antagonist [68 Ga]Ga-NOTA-PEG3 -RM26 performed better than an agonist [68 Ga]Ga-BBN when compared in a clinical study [19]. Modification of the chelator causes a re-distribution in charge and lipophilicity of the labeled peptide affecting its affinity and off-target interactions in vivo. In vivo evaluation of mercaptoacetyl-containing peptide-based chelators for 99m Tc-labeling of GRPR antagonists has not been published so far. PEG2 -RM26), to be suitable for direct labeling with 99m Tc. The main aim of99m this study was study was to provide a radiotracer that will be simple to radiolabel with Tc and to use to provide a radiotracer that will be simple to radiolabel with 99m Tc and to use in clinics for in clinics for imaging GRPR-overexpressing prostate cancers
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