KOMU Interview with Kattesh Katti, PhD

Prostate Cancer Treatment Using Nanotechnology Yields Promising Research Results

MU scientists publish unprecedented tumor reduction findings in international peer-reviewed journal

After a prostate tumor grows to a certain size, it becomes difficult to remove surgically, leaving few treatment options. But MU researchers have made a discovery that may change that outcome — a new treatment using engineered radioactive gold nanoparticles that reduce the size of prostate cancer tumors in mice.

Co-principal investigators Kattesh Katti, PhD, and Raghuraman Kannan, PhD, with the University of Missouri School of Medicine Department of Radiology, have been studying the new therapy for more than four years. They are in the process of applying to perform clinical trials in humans.

"We're encouraged by the results of this study and its implications," Katti said. "Reduction in tumor volume has a direct impact on the effectiveness of chemotherapy and immunotherapy in a cancer patient, and it also been associated with slowing down a cancer's metastasis and invasion."

The American Cancer Society estimates 192,280 men are diagnosed with prostate cancer every year, resulting in loss of life for 27,360 men in the United States and 288,000 men worldwide if not treated in time. It is the second most deadly cancer in men, after lung cancer.

Katti and Kannan's therapeutic efficacy studies carried out in prostate tumor bearing mice have demonstrated unprecedented 82 percent reduction in tumor volume after a single dose administration of the radioactive gold nanoparticle, GA-198AuNP. Their results appear in the international journal Nanomedicine: Nanotechnology, Biology, and Medicine.

"There are limited clinical interventions for treating advanced stage prostate and pancreatic cancers. Therapeutic efficacy of radioactive gold nanoparticles, as demonstrated in animal models by Dr. Katti and Dr. Kannan, present realistic potential for clinical translation for use in cancer patients," said Debabrata Mukhopadhyay, PhD, professor of biochemistry and molecular biology at the Mayo Clinic and an expert in tumor angiogenesis and vascular biology.

MU researchers have observed limited or no side effects as a result of the injected dose, which has been a challenge presented by other current prostate cancer treatments that target the tumor vasculature, or blood vessel network.



"Even though these agents are effective, many times their size doesn't match up with the size of the tumor blood vessels, which can cause the therapeutic agents to leak out significantly. This reduces the effectiveness of the treatment in killing tumor cells," Kannan said "However, our agent is a perfect fit for the porous tumor vasculature, leading to little or no side effects."

The MU Research Reactor (MURR) is one of only a few sites worldwide with the ability to produce gold nanoparticles. In 2006, Katti received a prostate cancer research grant that distinguished MU as one of only 12 universities to participate in the National Cancer Institute's national nanotechnology platform partnership. MU faculty members with MURR, the College of Veterinary Medicine, Department of Chemistry and others collaborated on the research project.

The project has been supported by grants from the National Institutes of Health, Nanoparticle Biochem Inc., the University of Missouri Research Board, and private endowment.

"This is probably the most promising result we could expect," said Andrew Kurtz, PhD, a program manager at the National Cancer Institute's Small Business Innovation Research Development Center. "The next stage would be to hopefully move things into clinical trials to see if we find the same results in humans."

Katti is a Curators' Distinguished Professor in Radiology and Physics and Margaret Proctor Mulligan Distinguished Professor in Medical Research. Kannan is the Michael J. and Sharon R. Bukstein Distinguished Faculty Scholar in Cancer Research.

The research was discussed today at the Missouri Nano Frontiers symposium at the Christopher S. Bond Life Science Center.

The study Radioactive gold nanoparticles in cancer therapy: Therapeutic efficacy studies of 198AuNP-GA nanoconstruct in prostate tumor bearing mice is available online at www.nanomedjournal.com/inpress.

MU scientists participating in the study included: Cathy Cutler and David Robertson (MURR); Jeff Smith, John Lever and Evan Boote (Department of Radiology); Carolyn Henry, Sandra Axiak, Stan Casteel and Jimmy Lattimer (College of Veterinary Medicine); Silvia Jurisson (Department of Chemistry) and several postdoctoral fellows and staff—all working within the Cancer Nanotechnology Platform: Ravi Shukla, Nripen Chanda, Ajit Zambre, Kavita Katti and Genny Fent.