Abstract 5595: Imaging biomarker development for treatment efficacy for prostate cancer to the bone

Autor: Stephanie Galban, Craig J. Galbán, Benjamin A. Hoff, Joshua S. George, Jean-Christophe Brisset, Brian D. Ross, Alnawaz Rehemtulla
Rok vydání: 2013
Předmět:
Zdroj: Cancer Research. 73:5595-5595
ISSN: 1538-7445
0008-5472
DOI: 10.1158/1538-7445.am2013-5595
Popis: Approximately 70% of patients with late stage cancers metastasize to the bone. RECIST identifies these tumors as “unmeasureable” for therapeutic response assessment. Cabozantinib (CABO), a tyrosine kinase inhibitor of MET and VEGFR2, has shown promise as an effective therapy for metastatic prostate cancer to the bone. Patients treated with CABO showed a reduction in [Tc99m]-bone scan signal suggesting tumor response to treatment. Nevertheless, a return in signal to pre-treatment levels was observed in these patients following therapy completion. It has yet to be determined if the response observed in bone scans results from tumor death, changes in bone metabolism or vascular alterations in the tumor-stromal microenvironment resulting in reduced transport of the imaging tracer. The study objective was to assess tumor and bone response to CABO in an animal model of bone metastasis using a quantitative multi-modal imaging approach. Twenty-seven male SCID mice were implanted with PC3 cell line in the right tibia. PC3 cells were transfected with a plasmid expressing a bioluminescence imaging (BLI) reporter for measuring apoptosis. When tumor volumes reached 10mm3 by MRI, mice were distributed into 2 groups: CABO at 30 mg/kg (N=13) and vehicle (N=14). Treatments were delivered by oral gavage once a day for three weeks. Starting pre-treatment, MRI and BLI were acquired every third day and CT every week. Tumor and bone volumes were monitored by manually contouring volumes of interest (VOI) on anatomical MRI and CT images, respectively. The apparent diffusion coefficient (ADC), an indirect measure of tumor cellularity, was calculated from diffusion MRI. Mice treated with CABO were found to have significantly higher ADC values and slower growth profile than controls (p Citation Format: Joshua S. George, Craig J. Galban, Jean-Christophe Brisset, Benjamin Hoff, Stephanie Galban, Alnawaz Rehemtulla, Brian D. Ross. Imaging biomarker development for treatment efficacy for prostate cancer to the bone. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5595. doi:10.1158/1538-7445.AM2013-5595
Databáze: OpenAIRE
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