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

PURPOSE: Transforming growth factor β (TGFβ) 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 TGFβ has not been ideal. Targeting TGFβ 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 TGFβ-targeting peptide P144 coupled with [(68)Ga] in a PANC-1 tumor model. PROCEDURES: TGFβ-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 [(68)Ga] to achieve a stable TGFβ-targeting tracer [(68)Ga]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: [(68)Ga]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 [(68)Ga]Ga-P144 PET in vivo, especially in tumor tissue, had a high TGFβ-targeting specificity. [(68)Ga]Ga-P144 PET had ideal imaging efficiency in PANC-1 tumor-bearing mice, with high specificity in vivo and good tumor-targeting effect. CONCLUSION: [(68)Ga]Ga-P144 has relatively high specificity and tumor-targeted uptake and may be developed as a promising diagnostic tool for TGFβ-positive malignancies.