Abstract 4890: Diffusion-weighted MRI provides an early assessment of treatment response in a murine model of metastatic prostate cancer to the bone

Abstract

Abstract Ninety percent of patients with advanced prostate cancer develop metastases to the bone1. At present, there is no definitive means for assessing response to therapy, with RECIST identifying tumors in the bone as “unmeasureable”. Diffusion-weighted MRI (DW-MRI) is highly sensitive to microscopic changes in tumor tissue. Our goal is to use DW-MRI to detect and quantify changes in tumor tissue throughout therapy where the magnitude of the change could be related to the effectiveness of the treatment. Human prostate cancer (PC3) cells were implanted by direct intra-tibial injection into male SCID mice, which served as a model for prostate bone metastases. MRI experiments were performed on a 9.4T MRI. Upon identifying a tumor volume of ∼10mm3, animals were randomly distributed into 4 treatment groups: docetaxel 20 mg/kg i.p. dose once a week for 3 doses (qd7×3; N=5), fractionated radiation IR at 2 Gy/day 5x per week for 2 weeks (N=7), combined treatment (N=5) and control (N=6). Animals were imaged by DW-MRI in which the apparent diffusion coefficient was calculated from the DW images. Tumor volume and ADC measurements were acquired pre-treatment and on days 0, 1, 4, 7, and once per week after post-treatment initiation. Animals were removed from the study when the tumor reached a percent increase of 400% (5x the initial tumor volume). Group comparisons in MRI metrics were obtained using an unpaired Student t-test. Mice treated by Dox or IR had significant smaller increase in tumor volume compared to control mice. Combined treatment resulted in improved efficacy over lone therapies. This resulted in a significant decrease in tumor size. The Dox group showed an increase in ADC following the first administration and a slow decline in ADC values following day 4 post-treatment initiations regardless of additional treatments. ADC value for IR treated animals did not elevate above control until day 7. Combined treatment generated increased ADC values that were maintained throughout the treatment cycle. IR and Dox alone and in combination were effective as assessed by anatomical and DW-MRI. Those results demonstrate the potential of quantitative ADC map for assessing early response of metastatic cancer to the bone.