PET imaging with [68Ga]-labeled TGFβ-targeting peptide in a mouse PANC-1 tumor model

Purpose: Transforming growth factor beta (TGF beta) is upregulated in many types of tumors and plays important roles in tumor microenvironment construction, immune escape, invasion, and metastasis. The therapeutic effect of antibodies and nuclide-conjugated drugs targeting TGF beta has not been ideal. Targeting TGF beta with small-molecule or peptide carriers labeled with diagnostic/therapeutic nuclides is a new development direction. This study aimed to explore and confirm the imaging diagnostic efficiency of TGF beta-targeting peptide P144 coupled with [Ga-68] in a PANC-1 tumor model.Procedures: TGF beta-targeting inhibitory peptide P144 with stable activity was prepared through peptide synthesis and screening, and P144 was coupled with biological chelator DOTA and labeled with radionuclide [Ga-68] to achieve a stable TGF beta-targeting tracer [Ga-68]Ga-P144. This tracer was first used for positron emission tomography (PET) molecular imaging study of pancreatic cancer in a mouse PANC-1 tumor model.Results: [Ga-68]Ga-P144 had a high targeted uptake and relatively long uptake retention time in tumors and lower uptakes in non-target organs and backgrounds. Target pre-blocking experiment with the cold drug P144-DOTA demonstrated that the radioactive uptake with [Ga-68]Ga-P144 PET in vivo, especially in tumor tissue, had a high TGF beta-targeting specificity. [Ga-68]Ga-P144 PET had ideal imaging efficiency in PANC-1 tumor-bearing mice, with high specificity in vivo and good tumor-targeting effect.Conclusion: [Ga-68]Ga-P144 has relatively high specificity and tumor-targeted uptake and may be developed as a promising diagnostic tool for TGF beta-positive malignancies.