Metabolic Evaluation of Non–Small Cell Lung Cancer Patient–Derived Xenograft Models Using ¹⁸F-FDG PET: A Potential Tool for Early Therapy Response

Abstract

Lung cancer heterogeneity makes response to therapy extremely hard to predict. Patient-derived xenografts (PDXs) are a reliable preclinical model that closely recapitulates the main characteristics of the parental tumors and may represent a useful asset for testing new therapies. Here, using PET imaging, we investigated whether lung cancer PDXs reproduce the metabolic characteristics of the corresponding parental tumors. Methods: We performed longitudinal 18 F-FDG PET studies on 9 different PDX groups obtained by implanting primary-cancer fragments harvested from patients into mice. The SUV max of each PDX was calculated and compared with the SUV max of the corresponding parental tumor. Results: Tumor growth rate and uptake varied among the different PDXs and confirmed the preservation of individual characteristics. The intragroup reproducibility of PET measurements was good. Furthermore, PDXs from tumors with a higher metabolic rate displayed a rank order of uptake similar to that of the parental tumors. Conclusion: PDXs reproduced the glucose metabolism of the parental tumors and therefore represent a promising preclinical model for the early assessment of therapy efficacy.

Patient-derived xenografts, a multi-faceted in vivo model enlightening research on rare liver cancer biology

“…More importantly also key physiopathological properties were preserved including growth properties and secretion of alpha-fetoprotein (AFP): interestingly one PDX model generated from an aggressive AFP-negative HB maintained low levels of secretion when implanted in mice. The maintenance of key biological and metabolic properties in PDXs is in line with the recent observation of preservation of glucose metabolism as measured by FDG-PET measurements in lung cancer-derived PDXs (10). Finally the different PDXs showed variable response to standard treatment (cisplatin) demonstrating representation in this platform of the heterogeneity observed in the clinic.…”

Noninvasive Detection of HER2 Expression in Gastric Cancer by 64Cu-NOTA-Trastuzumab in PDX Mouse Model and in Patients

“…Another investigation based on the type of animal models used for radioprobes evaluation in JNM form Aug 2014 to Aug 2016 was conducted. Only three types, glioblastoma, , small cell lung cancer, , and breast cancer, of patients of PDX were reported. In this study, we built HER2 positive (case 176) and HER2 negative (case 168) PDX tumor models based on two gastric cancer patients (Table ).…”

Metabolic classification of non-small cell lung cancer patient-derived xenografts by a digital pathology approach: A pilot study

“…In this pilot study, we tested the feasibility of this approach in a small subset of NSCLC PDX, previously established and characterized by M. Moro et al (23). These NSCLC PDX retained the key genetic alterations of the matched patients tumor samples and were also shown to reproduce their main metabolic features, as shown by [18F]FDG PET imaging studies (41).…”