Dataset Information

Preclinical Evaluation of ^99mTc-Labeled GRPR Antagonists maSSS/SES-PEG₂-RM26 for Imaging of Prostate Cancer.

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-PEG_2-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.

SUBMITTER: Abouzayed A

PROVIDER: S-EPMC7912279 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Publications

Preclinical Evaluation of <sup>99m</sup>Tc-Labeled GRPR Antagonists maSSS/SES-PEG<sub>2</sub>-RM26 for Imaging of Prostate Cancer.

Abouzayed Ayman A Rinne Sara S SS Sabahnoo Hamideh H Sörensen Jens J Chernov Vladimir V Tolmachev Vladimir V Orlova Anna A

Pharmaceutics 20210130 2

<h4>Background</h4>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 <sup>99m</sup>Tc can be utilized to facilitate the use of GRPR-targeting radiotracers for diagnostics of prostate cancers.<h4>Methods</h4>Synthetically produced mercaptoacetyl-Ser-Ser-Ser (maSSS)-PEG<sub>2</sub>-RM26 and mercaptoacetyl-Ser-Glu-Ser (maSES)-PE ...[more]

PMID: 33573232

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