Renal capsule patient-derived xenograft model for gastric cancer: establishment and MRI characterization

TL;DR

This study establishes a gastric cancer patient-derived xenograft model under the mouse kidney and identifies optimal conditions for tumor growth and MRI imaging techniques.

Contribution

The study identifies optimal tumor fragment size and transplantation timing for successful engraftment and evaluates MRI parameters for monitoring gastric cancer xenografts.

Findings

2×2×2 mm tumor fragments transplanted within 2 hours had the highest engraftment success rate.

T2-weighted MRI was most effective for detecting and measuring tumor size in xenografts.

PDX tumors retained histological and Ki67 expression features of primary tumors across generations.

Abstract

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.

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.

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.

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.

Figures