At AACR 2012, please join us at the poster presentations by Dr. Rao V. L.

Papineni,
1, Section 14, Tuesday Apr 3, 2012 1:00 PM - 5:00 PM

in vivo Imaging of early inflammation response in bacterial infection Staphylococcus aureus (S. aureus) causes significant morbidity and mortality worldwide and a prime cause in hospital infections. Staphylococcus aureus bactereremia is prevalent in neutropenic cancer patients, and malignancies form a sizeable risk factor for methycillin-resistant S. aureus (MRSA) infections. Targeting the virulence products is a promising approach for developing novel therapeutics. A detailed understanding of the virulence factors and the resultant immune response is quite essential for such development. Here, we established an athymic mice model to assess the initial immune response to S.aureus inoculation. As the polymorphonuclear neutrophils (PMN) and macrophages are a part of the early response, determination of its myeloperoxidase (MPO) activity in vivo is established. MPO is an inflammatory heme protein and utilizes hydrogen peroxide in the process of reactive oxygen species generation. 24 hrs after the intra muscular injection of the S.aureus bacterial lysate, the MPO activity was detected by i.p injection of luminal in mice. The blue luminescence resulting from the MPO activity was imaged with a commercially available multimodal imaging system. The luminescence images were overlaid on planar X-ray images for anatomical co-registration. The results show a robust MPO activity in the mouse bladder. This increase in MPO activity as a result of neutrophil activation at the bladder region was further confirmed using noninvasive X-ray contrast imaging of the bladder and co-registering the luminescence and the X-ray density signals at the bladder. The initial response shown here has similarities with the mechanism suggested recently for myobacterium bovis bacillus Calmette-Guerin (BCG) treatment of bladder cancer. Bacterial components, its structures that are involved in eliciting the robust PMN infiltration in bladder will be very valuable in the developing better bladder cancer anti-tumor treatments.
2, Section 15, Wednesday Apr 4, 2012 8:00 AM - 12:00 PM

Non invasive determination of in vivo myeloperoxidase activity in ovarian cancer mouse model. Myeloperoxidase (MPO) is an inflammatory heme protein present in myeloid cells- neutrophils, microglia, and macrophages. The enzyme activity of MPO utilizes hydrogen peroxide in the process of reactive oxygen species generation. Myeloperoxidase has been suggested recently as a likely marker in ovarian carcinoma. This relationship between the MPO and ovarian cancer however was deduced primarily from data obtained from in vitro studies using cancer cell lines and from immunostaining of ovarian carcinoma paraffin blocks. Real-time determination of in vivo MPO activity in the tumor and during the progression of ovarian cancer will be valuable to assess the role of innate immune process in ovarian cancer progression, in cancer treatment, and the proper management of current therapies. Here, we developed non invasive methodologies to determine the MPO activity in intraperitoneal ovarian cancer tumor mouse model. Tri-modal non invasive imaging of the metastatic ovarian cancer in athymic mice model were performed to obtain fluorescence, luminescence, and X-ray images at different time points during the progression of the intraperitoneal tumor metastasis. Progression of the tumor metastasis was monitored using fluorescence; simultaneously MPO activity was obtained by luminescence imaging. The MPO activity was detected by i.p injection of Luminol (5-amino-2,3-dihydro-1,4-phthalazine-dione) in physiological buffered saline (5 mg / 25gm mice). Luminol a redox-sensitive compound emits blue luminescence upon exposure to oxidizing agents, and in vivo, and has been established to have unique specificity to MPO activity. The fluorescence and luminescence images were overlaid on planar X-ray images for anatomical coregistration. The results show a robust increase in MPO activity in the mouse with the tumor development as compared to the control mice of the same cohort. Increase in MPO activity as a result of neutrophil activation was observed in the early phase of the ovarian cancer progression, and this increase subsides in the latter stages. However, the lumiscence signal intensities vary between the tumors, and near negligible MPO activity was observed in some tumors indicating a differential tumor microenvironment within the mouse. Further, the activity is far greater, at least in the initial stages, at the lung, nasal and other distal regions when compared to the intraperitoneal tumors. These real-time monitoring methodologies of MPO activity by in vivo imaging will greatly enhance the understanding of the tumor microenvironment during ovarian cancer progression, and contribute significantly in the development of better cancer treatments.

Dr. Rao V. L. Papineni is currently the Senior Principal Investigator, Research and Development, at Carestream Health Inc, USA. He received his doctoral degree in Biochemistry from University of Hong Kong (British Terr). Dr. Papineni had his early education from University of Madras, where he earned his Bachelors and Masters degree. After ten years in Research and Faculty positions at University of Hong Kong and Baylor college of Medicine (USA), he joined Kodak, USA five years ago. He has initiated advanced research programs to study Inflammation and musculo-skeletal biology utilizing molecular imaging and nanotechnology based molecular tools. Dr. Papineni has made several inventions and chaired scientific sessions in International Biomedical Meetings and serves on the editorial board of Nanotech and Experimental Pharmacology journals.

"Molecular Imaging - Wisdom To See For Maladies To Flee" Dr. Rao V. L. Papineni