Orthotopic Versus Allotopic Implantation: Comparison of Radiological and Pathological Characteristics

BACKGROUND: In experimental animal models, implantation location might influence the heterogeneity and overall development of the tumor, leading to an interpretation bias. PURPOSE: To investigate the effects of implantation location in experimental tumor model using magnetic resonance imaging (MRI) and pathological findings. STUDY TYPE: Prospective. SUBJECTS: Forty‐five breast cancer‐bearing mice underwent orthotopic (N = 15) and heterotopic (intrahepatic [N = 15] and subcutaneous [N = 15]) implantation. FIELD STRENGTH/SEQUENCE: Sequences including: T1‐weighted turbo spin echo sequence, T2‐weighted blade sequence, diffusion‐weighted imaging, pre‐ and post‐contrast T1 mapping, multi‐echo T2 mapping at 3.0 T. ASSESSMENT: MRI was performed at 7, 14, and 21 days after implantation. Native T1, post‐contrast T1, T2, and apparent diffusion coefficient (ADC) of tumors, the tumor volume and necrosis volume within tumor were obtained. Lymphocyte cells from H&E staining, Ki67‐positive, and CD31‐positive cells from immunohistochemistry were determined. STATISTICAL TESTS: One‐way analysis of variance and Spearman's rank correlation were performed. P value <0.05 was considered statistically significant. RESULTS: The tumor volume (intrahepatic vs. orthotopic vs. subcutaneous: 587.50 ± 77.62 mm(3) vs. 814.00 ± 43.85 mm(3) vs. 956.13 ± 119.22 mm(3)), necrosis volume within tumor (89.10 ± 26.60 mm(3) vs. 292.41 ± 57.92 mm(3) vs. 179.91 ± 31.73 mm(3), respectively), ADC at day 21 (543.41 ± 42.28 vs. 542.92 ± 99.67 vs. 369.83 ± 42.90, respectively), and post‐contrast T1 at all timepoints (day 7: 442.00 ± 11.52 vs. 435.00 ± 22.90 vs. 394.33 ± 29.95; day 14: 459.00 ± 26.11 vs. 436.83 ± 26.01 vs. 377.00 ± 27.83; day 21: 463.50 ± 23.49 vs. 458.00 ± 34.28 vs. 375.00 ± 30.55) were significantly different between three groups. Necrosis volumes of subcutaneous and intrahepatic tumors were significantly lower than those of orthotopic tumors. The CD31‐positive rate in the intrahepatic implantation was significantly higher than in orthotopic and subcutaneous groups. Necrosis volume (r = −0.71), ADC (r = −0.85), and post‐contrast T1 (r = −0.75) were strongly correlated with vascular invasion index. DATA CONCLUSION: Orthotopic and heterotopic tumors have their unique growth kinetics, necrosis volume, and vascular invasion. Non‐invasive MR quantitative parameters, including ADC and post‐contrast T1, may reflect vascular invasion in mice. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 3