Elastin-Specific Molecular Magnetic Resonance Imaging Reveals Spatiotemporal Extracellular Matrix Remodeling at the Tumor-Stroma Interface During Prostate Cancer Progression.

Abstract

Objectives: Extracellular matrix (ECM) remodeling is a hallmark of tumor progression, yet the longitudinal dynamics of elastin accumulation during prostate cancer (PCa) development remain unknown. This study aimed to longitudinally track elastin remodeling during PCa progression using elastin-specific molecular MRI (ESMA) in an orthotopic mouse model and to characterize the spatial heterogeneity of elastin deposition at the tumor-stroma interface.

Materials and methods: Human PC3 prostate cancer cells were orthotopically implanted into the ventral prostate lobe of SCID mice (n=6). Weekly MRIs were performed over 6 weeks at 3.0 Tesla using the gadolinium-based elastin-specific probe ESMA (0.2 mmol/kg intravenous weekly). Signal intensity (SI) was quantified before and after contrast administration. Findings were validated by Elastica-van Gieson staining, immunofluorescence, Western blot analysis, and laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) for spatial gadolinium mapping.

Results: Postcontrast SI increased progressively from 1517±151 at baseline to 3400±411 at week 6 (2.2-fold increase, P <0.001), with the most pronounced enhancement between weeks 2 and 3. Elastin distribution was spatially heterogeneous: peripheral tumor regions contained significantly more elastin (2.95±1.63%) than central areas (1.00±0.40%, P <0.008), indicating preferential ECM remodeling at the tumor-stroma interface. LA-ICP-MS demonstrated a strong correlation between gadolinium concentration and histologic elastin content ( R2 =0.88, P <0.001), and Western blot detected tropoelastin expression in all tumors.

Conclusion: ESMA-enhanced molecular MRI captures the longitudinal dynamics of elastin accumulation during PCa progression. Progressive elastin deposition, concentrated at the tumor periphery, is consistent with active ECM remodeling at the invasive front and suggests elastin as a candidate imaging biomarker for monitoring matrix-driven tumor progression.