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

Abstract

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 [¹⁸F]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 [¹⁸F]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 [¹⁸F]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 [¹⁸F]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 mm³, range: 3 mm³ to 584 mm³), lung tumors tended to have a more pronounced negative spatial relation of [¹⁸F]FLT and ADC with increasing tumor size. However, due to the low number of large tumors (> ~ 200 mm³), 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 [¹⁸F]FLT PET, cannot be detected in the experimental datasets investigated in this study.

Keywords: DW-MRI; Oncology imaging; Preclinical imaging; Voxel-analysis; [18F]FLT PET.