⁶⁸Ga-Labeled GX1 Dimer: A Novel Probe for PET/Cerenkov Imaging Targeting Gastric Cancer

Area of Science:

• Nuclear medicine
• Radiopharmaceutical chemistry
• Oncology imaging

Background:

• Gastric cancer diagnosis relies on accurate imaging techniques.
• Targeted molecular imaging probes enhance diagnostic specificity and sensitivity.
• GX1 is a peptide targeting gastric cancer, but its dimeric form may offer improved properties.

Purpose of the Study:

• To synthesize and characterize the dimer of GX1, termed KEK-(GX1)2.
• To evaluate the in vitro and in vivo performance of the radiolabeled dimer, 68Ga-DOTA-KEK-(GX1)2, for gastric cancer imaging.
• To compare the affinity, specificity, and tumor-targeting efficacy of the dimer probe against the monomeric GX1 probe.

Main Methods:

• Radiolabeling of DOTA-KEK-(GX1)2 with Gallium-68 (68Ga).
• In vitro assays including cell binding, competitive inhibition, immunofluorescence, and uptake/efflux studies.
• In vivo studies using nano PET/CT, Cerenkov imaging, and biodistribution in tumor-bearing nude mice.

Main Results:

• High labeling yield (>97%) and stability (>90 min in serum) of 68Ga-DOTA-KEK-(GX1)2.
• The dimer exhibited significantly higher binding affinity and specificity to target cells compared to the monomeric GX1.
• In vivo imaging demonstrated superior tumor targeting, with higher standardized uptake values (SUV) and signal-to-background ratios (SBR) for the dimer probe.

Conclusions:

• The dimeric modification of GX1 significantly enhances its in vitro and in vivo properties.
• 68Ga-DOTA-KEK-(GX1)2 is a promising radiotracer for PET and Cerenkov imaging of gastric cancer.
• This novel probe offers a potential advancement in the diagnostic capabilities for gastric cancer.