One in six American men gets prostate cancer eventually, but figuring out whether a man has it is not a one-step affair - a digital rectal exam and a PSA blood test lead to biopsy and maybe to an ultrasound exam. Even when a man clearly does have prostate cancer, knowing how serious and fast-growing his disease is, and whether it has grown back and spread despite treatment, continue to be vexing problems.

Researchers now are improving imaging techniques that better detect and define the scope of metastatic prostate cancer. The refined methods are gaining favor as a means for seeing whether treatment has succeeded in killing tumor tissue or whether cancer has recurred despite treatment. Because the techniques can be used to track specially tagged molecules introduced into the body, they seem likely to find broader application as ever more-targeted drugs and diagnostics become available.

Bruce Hasegawa, a professor of radiology at UCSF with a doctorate in medical physics, focuses on combining two different kinds of imaging as a way of seeing the best of both worlds. In collaboration with UCSF radiologists Benjamin Franc, David Price and Randall Hawkins, and with support from a state-funded UC Discovery Grant, co-sponsored by GE Medical Systems, Hasegawa is evaluating whether this new approach will improve the precision with which metastatic prostate cancer can be located and monitored with an antibody tracer (ProstaScint, made by Cytogen Corp.).

Hasegawa marries computed tomography (CT), for picturing anatomy, with single photon emission computed tomography (SPECT), for monitoring physiological function and biochemical events at the molecular level. "In our laboratory, over the last 15 years or so we have built imaging systems that do both, so that we can correlate anatomy and physiology in a direct way," Hasegawa says. "It seems like a simple thing to do, but nobody had really attacked it systematically before."

In a CT exam, unlike a simple X-ray exam, detectors record the impact of X-rays that have passed through the body sequentially from many directions. Technicians use system software to transform these multiple snapshots into three-dimensional images. With SPECT, small amounts of radioactive tracers are injected directly into the patient, where they target specific tissues of interest. A "gamma camera," actually a specialized detector, rotates to detect gamma radiation emitted from the tracer from all angles, and, as with CT, experts use specialized software to produce three-dimensional images.

Finding ways to accurately superimpose images from CT and SPECT examinations has been challenging for Hasegawa and other researchers, but now their advances are providing images that allow clinicians to see exactly where cancer has spread. The development of accurate and sensitive CT/SPECT imaging systems by Hasegawa and colleagues has led companies to commercialize the technology. In just the past few years, hundreds of CT/SPECT systems have already been put to use in hospitals across the country.

Hasegawa has won a second UC Discovery Grant, with Photon Imaging, Inc. as the industry co-sponsor, to use CT/SPECT to improve imaging in mice. The reliable rodents are increasingly used to model the genetic and molecular bases for a wide range of human diseases, and for evaluating new treatment concepts and drug prototypes.

Conventional ways of accurately tracking disease and treatment responses in mice rely on surgical procedures in which the animal is sacrificed. "This makes it impossible to follow the progression of disease in a single animal, or to obtain objective measurements before and after the animal receives a drug for diagnosis or treatment of a disease," Hasegawa explains. With CT/SPECT, for many studies researchers will not need to sacrifice a mouse to get results.

Dual modality imaging of anatomy and physiologic function may be the wave of the future, but the choice is not limited to CT/SPECT. Hasegawa's Department of Radiology colleague John Kurhanewicz is combining two nonradiographic techniques: Magnetic resonance imaging (MRI), to trace anatomy, and magnetic resonance spectroscopy (MRS), to track function. According to Hasegawa, "Magnetic resonance techniques are very good for looking at the local region around the prostate, and our techniques are suitable for looking at regions beyond the prostate." The best of both worlds, times two.