Images from left: Philip’s Skylight gamma camera, two 180-degree SPECT images; Siemens’ e.Cam Duet

For men diagnosed with prostate cancer, a number of treatment options exist, with differing side effects, and the choice can be difficult to make. Patients with low prostate specific antigen (PSA) levels or low Gleason scores are at low risk for metastatic spread, and many patients opt for local treatments, such as surgery to remove the prostate or radiotherapy. But for about half of those who undergo surgery the cancer has already spread beyond the prostate, rendering the surgery non-curative. To more accurately stage cancer before treatment, a growing number of physicians are turning toward metabolic or functional imaging to help determine if the cancer has spread and, therefore, determine the best course of treatment.

Although the use of metabolic imaging is still quite low, one type — nuclear imaging — is gaining some ground. Magnetic resonance spectroscopy (MRS) also is becoming more popular among some physicians. As in other areas of nuclear imaging, fusing anatomical images with the metabolic nuclear scans is poised to help increase nuclear’s popularity in prostate staging. Instead of the more widely known PET/CT, the fusion of positron emission tomography and computed tomography, prostate cancer staging is benefiting from combining CT with SPECT, or single photon emission computed tomography, though PET has its place in prostate cancer as well.

Cancer hot spots
ProstaScint, made by Cytogen Corp. (Princeton, N.J.), currently is the only imaging agent on the market that targets prostate-specific membrane antigen (PSMA), a marker found on prostate cancer cells, though other companies are working on PSMA-targeted agents as well. ProstaScint, an Indium-111-labeled monoclonal antibody, detects and localizes prostate cancer that has metastasized locally or beyond the prostate bed to lymph nodes, bones or other organs using SPECT. By imaging the patient with a gamma camera that detects the radiolabeled Indium, prostate cancer shows up as a hot spot on the nuclear image.

Charles Myers, M.D., a medical oncologist and director of the American Institute for Diseases of the Prostate (Charlottesville, Va.), a second opinion clinic for prostate cancer patients, says he regularly sees patients scheduled for surgery who have no chance of being cured by surgery alone. He uses ProstaScint scans to identify those patients and to help him determine the best course of treatment. “There really isn’t anything that competes,” he says. “It’s by far the most sensitive technique that we have to identify where the cancer has spread. It picks up metastatic disease too small to be identified by any other means.”

Although ProstaScint can save patients from unnecessary surgery by detecting metastatic spread, Myers says he also sees patients who have opted for chemotherapy, an often ineffective treatment option for prostate cancer, but who would be better served with a localized treatment, normally in patients whose cancer has returned after previous treatment. A ProstaScint scan can determine if the cancer that has returned is localized and therefore radiotherapy or surgery would be a better treatment option.

Despite its benefits, nuclear imaging of the prostate is not widely performed in the United States. The No. 1 reason, nuclear imagers say, is that the scans are difficult to interpret, particularly for radiologists accustomed to reading anatomical scans. Hotspots that can look like cancer may occur in the bladder, bowel or vascular structures, leading to false positive readings for metastatic disease.

But D. Bruce Sodee, M.D., associate professor or radiology and nuclear medicine at University Hospitals of Cleveland and one of the leading advocates for nuclear imaging of the prostate, says he has seen a growing interest in the technique among radiologists and urologists over the past two years. He attributes that change, in part, to the advent of fusion imaging. “We’ve markedly improved our accuracy,” says Sodee, who performs a ProstaScint scan on about four patients a week. “For the last 300 patients, ProstaScint/SPECT images have been fused with corresponding CT images which has increased our diagnostic accuracy.”

Samuel Kipper, M.D., director of nuclear medicine and PET imaging at Pacific Coast Imaging (Irvine, Calif.), agrees. He considers fusing ProstaScint scans with anatomical scans vital and has not performed a ProstaScint scan without fusion imaging since he added the capability about a year ago. “The advantages of fusion are it improves the accuracy of the test, it improves our ability to localize abnormalities, and it helps to localize normal findings to avoid false positive results,” he says. By overlaying the nuclear images with its hotspots onto the anatomical images, physicians can rule out those spots showing up in the bowel or bladder, for example, and they can see exactly where the cancer has spread.

GE Medical Systems’ Millenium VG Hawkeye gamma camera

Kipper says he uses ProstaScint on patients who have been newly diagnosed with cancer and are at a high risk for metastatic spread, such as those with high or rapidly rising PSA levels or high Gleason scores. But most of the patients are those that had a local treatment years earlier and now have rising PSA levels, indicating that the cancer has returned. “The best test to find out where it’s come back is a ProstaScint scan,” Kipper says. But to be effective, the facility must have experience interpreting the images. “The biggest problem with ProstaScint are cancer centers where the radiologist doesn’t have experience interpreting them,” he says, adding that some facilities may perform only one ProstaScint scan a month or even just a couple each year. Because of the difficulty interpreting nuclear images, patients should be referred to facilities that perform the procedure routinely, and better yet, to a facility with fusion imaging capabilities.

Nuclear equipment
About 37 centers offer ProstaScint imaging nationwide, says F. David Rollo, M.D., Ph.D., chief medical officer of nuclear medicine at Philips Medical Systems (Bothell, Wash.). “That’s up significantly from the number of centers a couple of years ago in large part because of the acceptance of the information as definitive in making the diagnosis and showing evidence of metastasis of disease,” Rollo says. “The increased accuracy of putting CT on top of either the positron emission tomography or the ProstaScint scan is really dramatic.” Although more facilities are using ProstaScint, only about seven facilities fuse ProstaScint with CT. One reason for the reluctance is the investment in special equipment required.

Rollo says that all of the manufacturers recognize the importance of SPECT/CT in prostate imaging and are developing devices that can achieve co-registration. Besides providing an anatomical map for the nuclear scan, the CT provides attenuation correction, which corrects for the difference in absorption rates of the gamma rays as they pass through different parts of the body. “When we do that correction, we end up with a picture that’s a better representation of the true activity and the exact location within the body,” Rollo says.

Manufacturers offer two methods for achieving co-registration between metabolic and anatomical images. One technique combines a nuclear imaging camera and CT into one device. Jeff Kao, global general manager for nuclear medicine at GE Medical Systems (GEMS of Waukesha, Wis.) says his company’s SPECT/CT device, the Hawkeye, conveniently merges the functional and anatomical information together into one easy-to-use device. Although the CT is not diagnostic quality, it provides the anatomical information physicians need to help interpret ProstaScint scans, Kao says, adding that the Hawkeye has been available for three years and sells for $100,000 and $150,000. Two hundred systems have been installed worldwide. In addition to prostate imaging, the device can be used in cardiology and the localization of other types of tumors.

SPECT/CT also can be achieved using special software that combines the images taken from a nuclear device and a separate CT or magnetic resonance (MR) device into a single image. Lin Sinclair, CNRT, clinical development specialist with Toshiba America Medical Systems (TAMS of Tustin, Calif.), says that fusion software has been talked about for the past five years, but only in the last few years have the workstations become powerful enough to achieve co-registration. TAMS and Siemens Medical Solutions Inc. (Malvern, Pa.) co-developed and now separately distribute e.soft fusion software, which Sinclair says has been available since April 2002 and is now part of the standard workstation shipped to Toshiba T.CAM nuclear camera customers.

The T.CAM and e.soft workstation also allow dual isotope studies, Sinclair says. When physicians perform a ProstaScint scan, they also can acquire a red blood cell vascular study. e.soft superimposes the two studies and displays them in two different colors. “The physician can easily see what’s a vascular structure and what is a tumor uptake,” she says. “Fusing images has become very sophisticated and dual isotope SPECT work has become more common.”

Gamma cameras used to take nuclear medicine images also are advancing. Most general gamma cameras use a three-eighth-inch crystal. Siemens, Toshiba and GEMS now sell cameras with a 1-inch segmented crystal. “The advantage is in medium and high energy imaging,” says Raffi Kayayan, Ph.D., product marketing manager of the nuclear medicine group at Siemens. “With the significant increase in system sensitivity by using a thicker crystal, it is now possible to either get a better image quality or to reduce the scan time or both. When you reduce the scan time, you increase patient comfort and at the same time you’re reducing the risk of patient motion.”

Siemens also recently introduced Flash 3D, an advanced SPECT reconstruction algorithm based on a fast 3D iterative reconstruction technique. Kayayan says the 3D reconstruction algorithm potentially can increase image contrast and improve lesion localization. “The difference in image quality between the new algorithm and the conventional Filtered Back Projection algorithm is really striking,” he says. University Hospitals’s Sodee has been working with Siemens to perfect 3D reconstruction and agrees that he can achieve better localization with the 3D images than with 2D on about half of his patients. He also uses Siemens Duet gamma camera with a 1-inch crystal and says the thicker crystal provides a 20 percent to 30 percent better count rate with In-111 than the five-eights-inch crystal of the Siemens e-cam+ camera.

Although most nuclear imaging of the prostate involves SPECT scanning, PET imaging also has a place, but is limited to fast growing, aggressive tumors. Because most prostate cancers have a slower metabolic uptake of glucose than other types of cancer, prostate cancer cells metabolize less of the fluorinated glucose used in PET imaging. Sodee says he has found that PET with FDG is only about 70 percent as effective as ProstaScint. But because PET does detect the more rare faster-growing prostate cancer cells, PET is useful in gauging whether a patient’s cancer is aggressive or non-aggressive.

The American Institute’s Myers says he would like to use PET on patients with aggressive forms of cancer, but Medicare does not reimburse PET’s use in prostate cancer. Patients must either pay for the procedure themselves or convince a private insurance company to pay. “So I use it less than I would like,” he says. “It’s definitely very useful in the most aggressive form of prostate cancer.”

Although the adoption of nuclear imaging of the prostate has been slow, physicians and manufacturers say its usefulness is too great to remain idle for long. Toshiba’s Sinclair says the technology in nuclear imaging of the prostate is complete and its adoption is dependent on physician awareness and use of fusing the nuclear scans with anatomical images. “If physicians can become more comfortable in reading the studies and interpreting the films so that the reputation of the test becomes stronger, than I would see a growth in it,” she says. “But at this time, without fusion and dual-isotope activities, I think a lot of hospitals stay away from nuclear imaging because of the difficulty in interpreting it.”

Physicians say that is slowly changing as urologists and radiation therapists begin to think metabolically and to understand the benefits. Radiation therapists performing brachytherapy, for example, can use the images to map the cancer within the prostate for better seed placement. “As people see the new images that Sodee is able to create, it’s making believers out of folks,” says Myers. “The fusion technique will spread and as it does, you’ll see a gradual growth in nuclear imaging’s use.”

The MRS option
Magnetic resonance spectroscopy (MRS) also offers an amalgamation of anatomic and metabolic information. Like SPECT/CT, the magnetic resonance imaging (MRI) and spectroscopy combination is used after diagnosis to better understand the volume and extent of disease. The information helps physicians determine the best course of treatment for the patient.

Adding spectroscopy software to an MR device is an easy addition, says Tom Raidy, Ph.D., MR spectroscopy engineering manager at GEMS. Although first used in the brain, MRS is becoming more popular as a prostate imaging tool as well. GEMS collaborated with the University of California-San Francisco, where the technique was developed, to create PROSE (Prostate Imaging and Spectroscopy Exam), GEMS’s MRS software product, which received FDA approval in August 2001 and is now found in about 20 facilities nationwide, Raidy says.

The addition of spectroscopy to high-resolution MR images increases the confidence rate of sensitivity and specificity to 95 percent, an advantage over the two modalities alone, Raidy says. “You need one for sensitivity and one for specificity. That’s the combination that seems to win,” he says. “It’s the difference between MRI being a useful tool in prostate disease to having MRS being very conclusively useful in prostate disease.”

The American Institute’s Myers says MRS primarily is used to detect extra-capsular extension. “It’s major downside is that if the patient has had a biopsy and has bled into the prostate then it creates a confusing image,” he says. “So it’s best to do it before the biopsy, but it’s usually after the biopsy that you think to do it.” Because of that, Myers says he prefers color Doppler ultrasound to MRS. Another hindering factor for widespread adoption is the high cost of MRS and the special skills required.

Physicians who use MRS recommend the technique be used before the biopsy and say the procedure can guide physicians to the exact location of the cancerous tissue, increasing the biopsy success rate. After a biopsy, physicians should wait six to eight weeks before performing MRS.

Philips’ Rollo says that MRS can provide the same information as a biopsy without requiring the invasive procedure. MRS has been around since the 1980s, but new multi-center trials are studying the procedure’s effectiveness in prostate imaging and as those studies are published, the technique will see greater acceptance. “People are just beginning to feel comfortable that the spectroscopy that they obtain in patients can be used to make a diagnosis,” Rollo says. “Prostate is just one area where this will be applied.”