Voxel-Based Analysis of the Relation of 3′-Deoxy-3′-[18F]fluorothymidine ([18F]FLT) PET and Diffusion-Weighted (DW) MR Signals in Subcutaneous Tumor Xenografts Does Not Reveal a Direct Spatial Relation of These Two Parameters

Purpose: Multimodal molecular imaging allows a direct coregistration of different images, facilitating analysis of the spatial relation of various imaging parameters. Here, we further explored the relation of proliferation, as measured by [F-18]FLT PET, and water diffusion, as an indicator of cellular density and cell death, as measured by diffusion-weighted (DW) MRI, in preclinical tumor models. We expected these parameters to be negatively related, as highly proliferative tissue should have a higher density of cells, hampering free water diffusion. Procedures: Nude mice subcutaneously inoculated with either lung cancer cells (n = 11 A549 tumors, n = 20 H1975 tumors) or colorectal cancer cells (n = 13 Colo205 tumors) were imaged with [F-18]FLT PET and DW-MRI using a multimodal bed, which was transferred from one instrument to the other within the same imaging session. Fiducial markers allowed coregistration of the images. An automatic post-processing was developed in MATLAB handling the spatial registration of DW-MRI (measured as apparent diffusion coefficient, ADC) and [F-18]FLT image data and subsequent voxel-wise analysis of regions of interest (ROIs) in the tumor. Results: Analyses were conducted on a total of 76 datasets, comprising a median of 2890 data points (ranging from 81 to 13,597). Scatterplots showing [F-18]FLT vs. ADC values displayed various grades of relations (Pearson correlation coefficient (PCC) varied from -0.58 to 0.49, median: -0.07). When relating PCC to tumor volume (median: 46 mm(3), range: 3 mm(3) to 584 mm(3)), lung tumors tended to have a more pronounced negative spatial relation of [F-18]FLT and ADC with increasing tumor size. However, due to the low number of large tumors (> similar to 200 mm(3)), this conclusion has to be treated with caution. Conclusions: A spatial relation of water diffusion, as measured by DW-MRI, and cellular proliferation, as measured by [F-18]FLT PET, cannot be detected in the experimental datasets investigated in this study.