Objective Pituitary neuroendocrine tumors (PitNETs) are common intracranial neoplasms that can exhibit invasive behavior, leading to increased morbidity, recurrence, and resistance to treatment. Identifying biomarkers associated with tumor invasiveness could improve early diagnosis and guide therapeutic interventions. This systematic review evaluates molecular biomarkers linked to PitNET invasiveness and explores the potential of radiolabeling for noninvasive detection. Methods A systematic search of PubMed and Embase databases was conducted to identify studies evaluating molecular markers associated with invasive PitNETs. Biomarkers were selected based on their proposed role in tumor invasion, and evidence supporting their clinical relevance was summarized. Additionally, existing radiolabeling techniques for biomarker detection were reviewed. Results Five key biomarker groups were identified: matrix metalloproteinases (MMPs), urokinase plasminogen activator (uPA) system, myosin 5A (MYO5A), vascular endothelial growth factor (VEGF), and survivin. MMPs were strongly linked to extracellular matrix degradation and invasion, while uPA facilitated invasion via MMP activation. MYO5A and survivin were implicated in epithelial-mesenchymal transition and tumor motility, and VEGF promoted angiogenesis. Radiolabeling techniques for MMPs, uPA/uPAR, VEGF, and survivin demonstrated feasibility for imaging tumor invasiveness, though limitations such as non-specific tracer accumulation remain. Conclusions This review highlights the potential of molecular biomarkers in predicting PitNET invasiveness and the emerging role of radiolabeled probes in noninvasive imaging. Future research should focus on validating these biomarkers in longitudinal studies and refining radiolabeling techniques to improve diagnostic accuracy and therapeutic targeting of invasive PitNETs.

The authors have declared no competing interest.

https://github.com/Pituitary-Normal-Space/database-searcher

This study did not receive any funding

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