Evaluation of early chemotherapy response by combining static- and dynamic [¹⁸F]FDG-PET with diffusion-weighted MRI in subcutaneous patient-derived endometrial cancer mouse models

Background: The combination of carboplatin and paclitaxel is the standard chemotherapy for treatment of high-risk and recurrent endometrial cancer. Evaluation of treatment response by diagnostic imaging is routinely carried out months after start of treatment, and is based on changes in tumor size or appearance of new metastases. The aim of this study was to evaluate early chemotherapeutic response in two subcutaneous endometrial cancer mouse models generated from patient-derived organoids using static- and dynamic [¹⁸F]fluorodeoxyglucose ([¹⁸F]FDG) positron emission tomography (PET) and diffusion-weighted (DW) magnetic resonance imaging (MRI). Mice were injected bilaterally with endometrioid endometrial cancer grade 3 (EEC G3), International Federation of Gynaecology and Obstetrics (FIGO) stage 3C1 (Model A) or stage 1B (Model B) organoids (n = 15 mice). The mice were randomized into treatment (combined carboplatin and paclitaxel, n_A=8 / n_B=6 tumors) or control (saline, n_A=8 / n_B=8 tumors) groups. During tumor progression, the mice underwent T2-weighted (T2w) MRI, DW-MRI and dynamic [¹⁸F]FDG-PET at baseline/Day 0 (start of treatment), Day 3 (early) and Day 10 (endpoint) using a sequential PET-MRI small-animal scanner. Results: At endpoint, tumor volumes at T2w-MRI (vMRI) were lower in the treatment groups in both models (p ≤ 0.029). The tumor metabolic rate (MR_FDG) from dynamic PET, was significantly lower in the treatment group at the early timepoint (Day 3) and at the endpoint in Model A (p ≤ 0.042). In Model B, MR_FDG was similar for both groups at Day 3 and at endpoint (p≥0.217). The 10 tumor voxels with the highest standardised uptake value (SUV₁₀) from static [¹⁸F]-FDG-PET was significantly lower at endpoint in the treatment groups in both models (p ≤ 0.041), but not at the early timepoint (p≥0.083). Similarly, the tumor apparent diffusion coefficient (ADC_mean) was significantly higher indicating treatment response at endpoint for treatment groups in both models (p ≤ 0.036). Conclusions: Multimodal imaging is feasible for evaluation of early signs of treatment response in preclinical subcutaneous endometrial cancer models. The novel MR_FDG dynamic PET imaging parameter seems most promising for detecting very early treatment response following chemotherapy.