Frontiers in immunology · 2025
Renal capsule patient-derived xenograft model for gastric cancer: establishment and MRI characterization.
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Yin Zhenyu, Liu Qian, Maswikiti Ewetse Paul, Wang Zhuanfang, Bai Yuping, Xiang Lin, Wang Yuhan, Ma Bin, Gao Lei, Shi Jianming, Chen Hao
Аннотация
OBJECTIVE: Identify factors associated with the engraftment of gastric cancer patient-derived xenograft (GC PDX) in the renal capsule and explore optimal MRI sequence parameters for observing renal capsule PDX.
METHODS: Tumor tissues from 33 gastric cancer patients were cut into fragments of 1×1×1 mm, 2×2×2 mm, and 3×3×3 mm, then transplanted beneath the renal capsule of NOD/SCID mice within 2, 8 and 24 hours. Depending on tissue availability, tumor samples from each patient were implanted into 1-4 mice, totaling 73 mice. Clinical data were collected. Tumor growth was monitored weekly via MRI. T1WI, contrast-enhanced T1WI, T2WI was used to measure tumor length. After euthanasia (10g/L sodium pentobarbital, 180mg/kg, intraperitoneal), tumors were excised, and caliper-measured were compared with MRI results. The xenografts were serially passage into new mice for three generations. Histopathological (H&E), Ki67 immunohistochemistry were performed to assess similarity with primary tumors.
RESULTS: Tumors from 20 out of 33 patients successfully engrafted in 28 out of 73 mice. The 2×2×2 mm grafts and transplantation in 2 hours had a higher success rate. Patient serum albumin was associated with successful engraftment. PDX exhibited isointense and hyperintense on T2WI and marked enhancement on T1WI post-contrast. No significant difference was observed between MRI and caliper-measured. H&E staining, Ki67 expression confirmed that PDX tumors retained histological features of primary tumors.
CONCLUSION: Optimal conditions for establishing GC PDX models involve transplanting 2×2×2 mm tumor fragments within 2 hours. MRI enables sensitive tumor detection and accurate size quantification. T2WI was the most effective and efficient imaging technique. Providing an efficient preclinical model for personalized therapy of gastric cancer.
METHODS: Tumor tissues from 33 gastric cancer patients were cut into fragments of 1×1×1 mm, 2×2×2 mm, and 3×3×3 mm, then transplanted beneath the renal capsule of NOD/SCID mice within 2, 8 and 24 hours. Depending on tissue availability, tumor samples from each patient were implanted into 1-4 mice, totaling 73 mice. Clinical data were collected. Tumor growth was monitored weekly via MRI. T1WI, contrast-enhanced T1WI, T2WI was used to measure tumor length. After euthanasia (10g/L sodium pentobarbital, 180mg/kg, intraperitoneal), tumors were excised, and caliper-measured were compared with MRI results. The xenografts were serially passage into new mice for three generations. Histopathological (H&E), Ki67 immunohistochemistry were performed to assess similarity with primary tumors.
RESULTS: Tumors from 20 out of 33 patients successfully engrafted in 28 out of 73 mice. The 2×2×2 mm grafts and transplantation in 2 hours had a higher success rate. Patient serum albumin was associated with successful engraftment. PDX exhibited isointense and hyperintense on T2WI and marked enhancement on T1WI post-contrast. No significant difference was observed between MRI and caliper-measured. H&E staining, Ki67 expression confirmed that PDX tumors retained histological features of primary tumors.
CONCLUSION: Optimal conditions for establishing GC PDX models involve transplanting 2×2×2 mm tumor fragments within 2 hours. MRI enables sensitive tumor detection and accurate size quantification. T2WI was the most effective and efficient imaging technique. Providing an efficient preclinical model for personalized therapy of gastric cancer.