Synergy Between Anti-CCL2 And Docetaxel As Determined By DW-MRI In A Metastatic Bone Cancer Model

Main Category: Urology / Nephrology
Also Included In: Cancer / Oncology;  Bones / Orthopedics
Article Date: 26 Apr 2009 - 2:00 PDT

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UroToday.com - In the Journal of Cellular Biochemistry, an international research group with Dr. Ken Pienta as senior author reports findings using diffusion-weighted MRI (DW-MRI) to image the response of prostate cancer (CaP) to treatment in the bone environment.

The experiments compared SCID mice treated with placebo, to ones treated with docetaxel, antibodies to CCL2 (monocyte chemoattractant protein-1) or both inhibitors. CCL2 is an important promoter of CaP metastasis and attracts macrophages to the tumor site promoting tumor cell proliferation, migration and survival. CCL2 antibodies in combination with docetaxel are known to inhibit CaP tumor grown in an animal model. DW-MRI is an imaging method for quantification of water diffusion values and is reported as apparent diffusion coefficient (ADC). ADC values increase in tumor regions undergoing a loss of cellular density. DW-MRI may provide an early indication of treatment response in CaP bone lesions.

Androgen-insensitive PC3 cells expressing luciferase that could be imaged by bioluminescence (BLI) were used in the experiments. In study 1, the effects of docetaxel, anti-CCL2 and a combination of the two agents were compared to control mice by using BLI imaging to assess growth of PC3-luciferase tumors. Significant inhibition of tumor growth was observed by BLI for all test groups, with the combination of docetaxel and anti-CCL2 having the greatest effect. Overall survival was greatest in this group as well at 22 weeks, compared to docetaxel alone at 15 weeks, anti-CCL2 antibodies at 11 weeks and control mice at 6 weeks. In study 2, the same treatment arms were assessed by DW-MRI. The goal was to evaluate the ability of DW-MRI to detect differential responses to the therapies based upon differences in the magnitude of changes in tumor water diffusion values. It is sensitive for the detection of cell death rather than cell cycle arrest. Baseline tumor diffusion values were low, but following 14 days of treatment, the docetaxel and combination treated mice had the largest shift in ADC values. This was consistent with BLI data.

These data suggest that DW-MRI may be a sensitive technology to assess early therapeutic response of CaP in the metastatic bone environment.

Rozel S, Galbán CJ, Nicolay K, Lee KC, Sud S, Neeley C, Snyder LA, Chenevert TL, Rehemtulla A, Ross BD, Pienta KJ
J Cell Biochem. 2009 Mar 3. Epub ahead of print.
doi:10.1002/jcb.22056

Written by UroToday.com Contributing Editor Christopher P. Evans, MD, FACS

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