Abstract 2539: Imaging heterogeneity in pre-clinical models of soft-tissue sarcoma with multi-parametric MRI

Abstract Soft tissue sarcomas (STS) are highly aggressive and heterogeneous cancers. There is a clinical need for techniques to image inter- and intratumoral heterogeneity of STS for personalized adaptation of treatment and to improve diagnostic accuracy. Multiparametric MRI (mpMRI) quantitatively maps spatial variations of functional and structural features of tumors in vivo. mpMRI data was acquired from mice bearing subcutaneous ICR-LMS-1, SK-UT-1 (both leiomyosarcoma, LMS) or HS-SY-II (synovial sarcoma, SS) xenografts. Biomarkers included quantification of the tumor apparent diffusion coefficient (ADC), native T1 and T2 relaxation times, magnetisation transfer ratio (MTR), the transverse relaxation rate R2*, and the complex shear modulus |G*| using MR elastography to assess tumor stiffness. Pathology correlates were sought from MRI-aligned histological sections. Frequency histograms visualized the distribution of values to assess statistical dispersion. Median ADC and T2 were significantly higher in the two LMS models compared to the more cellular dense HS-SY-II tumors (table Table ICR-LMS-1 (n=7) SK-UT-1 (n=8) HS-SY-II (n=10) Tumor volume (mm3) 374 ± 116 343 ± 26 405 ± 52 ADC (x10-6mm3/s) 1303 ± 139 1083 ± 91 629 ± 30 *** T1 (ms) 2549 ± 42 2607 ± 49 2496 ± 33 T2 (ms) 110 ± 14 96 ± 4.6 73 ± 2 *** MTR (%) 16.5 ± 6 20 ± 0.46 22 ± 0.41 * R2* (s-1) 31.7 ± 14.5 26 ± 1.5 43.7 ± 3.4 * G* (kPa) 3.46 ± 0.45 2.87 ± 1.02 4.06 ± 0.22 ). Significantly higher MTR in the HS-SY-II tumors suggests greater macromolecule (e.g protein) content. Tumor R2*, a proxy for blood vessels, was slowest in the SK-UT-1 cohort, consistent with their low CD31 positivity. All three models exhibited a relatively soft biomechanical phenotype. HS-SY-II tumors displayed unimodal histograms, suggesting homogeneously distributed MRI biomarkers, and had little inter-tumor variation. In contrast, both LMS models exhibited bi- or trimodal distributions and higher interquartile range values, particularly for ADC, indicating pronounced intratumor heterogeneity and marked inter-tumour variation. mpMRI can inform on and assess differences in tissue heterogeneity within STS subtypes. Quantification of tumor ADC may provide a sensitive MRI biomarker to assess differential response of LMS and SS to therapy, which has clear translational potential. Citation Format: Ellen O'Sullivan, Clémentine Lesbats, Paul H. Huang, James P. O'Connor, Simon P. Robinson. Imaging heterogeneity in pre-clinical models of soft-tissue sarcoma with multi-parametric MRI [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 2539.