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

Abstract

PurposeTransforming 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 [68Ga] in a PANC-1 tumor model.ProceduresTGFβ-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 [68Ga] to achieve a stable TGFβ-targeting tracer [68Ga]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[68Ga]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 [68Ga]Ga-P144 PET in vivo, especially in tumor tissue, had a high TGFβ-targeting specificity. [68Ga]Ga-P144 PET had ideal imaging efficiency in PANC-1 tumor-bearing mice, with high specificity in vivo and good tumor-targeting effect.Conclusion[68Ga]Ga-P144 has relatively high specificity and tumor-targeted uptake and may be developed as a promising diagnostic tool for TGFβ-positive malignancies.

TGF-β signaling: critical nexus of fibrogenesis and cancer

“…Mouse models and xenografts are frequently employed to replicate the complex tumor microenvironment and better understand the dynamic interactions between TGF-β signaling and cancer progression [ 134 – 136 ]. In addition, non-invasive imaging techniques, such as positron emission tomography (PET) and magnetic resonance imaging (MRI), have become increasingly valuable tools for tracking TGF-β signaling changes in pre-clinical animal models, offering crucial data on treatment efficacy and tumor behavior [ 137 – 141 ]. By combining in vitro and in vivo methods, the hope is that researchers will be able to further develop and refine their diagnostic and therapeutic strategies, ensuring more precise targeting of TGF-β pathways leading to improved patient outcomes in the long-term.…”