'Theranostic' imaging targets, kills only PCa cells

Experimenting with human prostate cancer cells and mice, cancer-imaging experts at Johns Hopkins University, Baltimore say they have developed a method for finding and killing malignant cells while sparing healthy ones.

The method, called "theranostic" imaging, targets and tracks potent drug therapies directly and only to cancer cells. It relies on binding an originally inactive form of drug chemotherapy, with an enzyme, to specific proteins on tumor cell surfaces and detecting the drug’s absorption into the tumor. The binding of the highly specific drug-protein complex, or nanoplex, to the cell surface allows it to get inside the cancerous cell, where the enzyme slowly activates the tumor-killing drug.

The authors say their findings, published online in American Chemical Society Nano (Aug. 9, 2012), are believed to be the first to show that chemotherapies can be precisely controlled at the molecular level to maximize their effectiveness against tumors, while also minimizing their side effects.

In the study, overseen by Zaver Bhujwalla, PhD, and co-investigator Martin Pomper, MD, PhD, the authors directed drugs only to cancer cells, specifically those with prostate-specific membrane antigen (PSMA).

"Our results show a noninvasive imaging approach to following and delivering targeted therapy to any cancer that expresses PSMA," said Dr. Bhujwalla.

The authors tested their ability to track with imaging devices the delivery of anti-cancer drugs directly to tumors. Some of the tumors were comprised of cells with PSMA, while "control" tumors had no PSMA. Included in the drug nanoplex were small strands of RNA. All nanoplex components were imaged inside the tumor, in addition to dropping choline kinase production, which decreased by 80% within 48 hours of nanoplex absorption into cells with ample PSMA.

When the authors used antibodies to block the action of PSMA, the level of nanoplex uptake and drug activation in cancerous cells went down as measured by dimming of the image.

Different concentrations of the drug nanoplex, tagged with radioactive and fluorescent molecules, were mixed in the lab with prostate cancer tissue cells, some of which had extra PSMA and others that had none. Only those cells with extra PSMA showed nanoplex uptake, as measured by image intensity, which later decreased when PSMA-blocking chemicals were added.

Additional experiments involving injections of three different concentrations of the drug nanoplex showed no damage to other vital mouse organs, such as the kidney and liver, nor any uptick in the mouse immune system response.

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