A Uniquely Modified DKL-based Peptide Probe for Positron Emission Tomography Imaging.

Area of Science:

• Radiochemistry
• Molecular Imaging
• Oncology

Background:

• The asparagine-glycine-arginine (NGR) motif targets the CD13 receptor, a biomarker for tumor neovasculature.
• D-K6L9 is an anti-cancer peptide with tumor-selective properties.

Purpose of the Study:

• To develop and evaluate a novel Gallium-68 (68Ga) labeled peptide probe for targeting CD13-positive tumors.
• To combine the tumor-targeting NGR motif with the tumor-selective D-K6L9 peptide and radiolabel it with 68Ga for imaging applications.

Main Methods:

• Synthesis of the NGR-D-K6L9 peptide conjugate (NKL) and its subsequent radiolabeling with 68Ga using 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA).
• In vitro characterization of 68Ga-DOTA-NKL stability in buffer and human serum.
• In vitro cellular uptake studies in CD13 receptor-positive 22Rv1 tumor cells.
• In vivo preclinical evaluation using positron emission tomography (PET)/computed tomography (CT) imaging in a human prostate cancer xenograft mouse model.

Main Results:

• 68Ga-DOTA-NKL demonstrated stability in vitro.
• Significant uptake of 68Ga-DOTA-NKL was observed in CD13-positive 22Rv1 cells.
• In vivo PET/CT imaging showed preferential accumulation of the probe in tumors, with tumor-to-background ratios reaching 9.97 ± 1.90.
• Tumor uptake of 68Ga-DOTA-NKL was observed to be 8.69 ± 0.20 %ID/g at 0.5 h post-injection, decreasing to 1.41 ± 0.23 %ID/g at 3 h post-injection.

Conclusions:

• The novel 68Ga-DOTA-NKL probe exhibits combined tumor-targeting and tumor-selective properties.
• This probe holds potential for the diagnosis of CD13-positive tumors.
• Further investigation is warranted for its clinical application in cancer imaging.