Renal capsule patient-derived xenograft model for gastric cancer: establishment and MRI characterization
Zhenyu Yin1, Qian Liu1, Ewetse Paul Maswikiti1
1The Second Hospital and Clinical Medical School, Lanzhou University, Lanzhou, China.
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.
Insights
Establishing gastric cancer patient-derived xenografts (GC PDX) is optimized by using 2×2×2 mm fragments transplanted within 2 hours. Magnetic resonance imaging (MRI) effectively monitors GC PDX growth and characteristics.
Area of Science:
- Oncology
- Preclinical Research
- Medical Imaging
Background:
- Gastric cancer patient-derived xenografts (GC PDX) are crucial for preclinical research.
- Optimizing the engraftment process and imaging techniques for GC PDX models is essential for advancing personalized therapy.
Purpose of the Study:
- To identify factors influencing the engraftment of gastric cancer patient-derived xenografts (GC PDX) in the renal capsule.
- To determine optimal MRI sequence parameters for monitoring GC PDX within the renal capsule.
Main Methods:
- Tumor fragments (1-3 mm) from 33 gastric cancer patients were transplanted into NOD/SCID mice within 2, 8, or 24 hours.
- Tumor growth was monitored weekly using MRI (T1WI, contrast-enhanced T1WI, T2WI), followed by ex vivo caliper measurements.
- Histopathological analysis (H&E, Ki67) was performed on xenografts and compared to primary tumors.
Main Results:
- Successful engraftment was achieved in 20 out of 33 patients (28/73 mice).
- Optimal engraftment conditions included 2×2×2 mm fragments transplanted within 2 hours; patient serum albumin correlated with success.
- MRI accurately quantified tumor size, with T2WI proving most effective; PDX retained primary tumor histology.
Conclusions:
- The study identified optimal conditions (2×2×2 mm fragments, <2-hour transplantation) for establishing GC PDX models.
- MRI, particularly T2WI, is a sensitive and accurate method for monitoring GC PDX.
- These findings facilitate the development of efficient preclinical models for personalized gastric cancer therapy.
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