Joining Forces: PET-CT Adds Essential Information

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The boldface headline on molecular imaging proclaims dramatic market shifts in the types of PET scanners being delivered, according to industry leaders. More than 95 percent of systems sold today are PET-CT hybrid scanners that combine to provide more applications and more imaging information than is possible separately.

Most positron emission tomography exams today are performed for clinical applications in oncology. However, when a high-speed multislice CT module is incorporated, the combined scanner offers opportunities for comprehensive cardiac studies that can reveal the extent of an ischemic area as well as the specific problem within the coronary vasculature that produced the presenting event.

The CT component enables whole-body attenuation correction and exquisite anatomic localization of lesions that yields impressive enhancements to accuracy in a number of applications. For example, when clinicians interpret studies obtained through an individual modality scan, the sensitivity and specificity may reside in the 60 percent and 70 percent range.  But when studies are completed in near simultaneous succession using a PET-CT, the accuracy rate rises to about 90 percent, according to Philips Medical Systems. Clinicians in the field corroborate this assessment. This improved precision affords a level of confidence in staging cancerous conditions, evaluating effectiveness of treatment and guiding biopsies of tumors and in the case of cardiac applications may decrease the necessity for further testing or invasive procedures through the use of CT angiography combined with PET imaging data.

Peter F. Faulhaber, MD, assistant professor of radiology at Case Western Reserve University, director of clinical PET at the University Hospitals in Cleveland and director of nuclear medicine at the Lewis Stokes Veterans Administration Medical Center, explains that when considering molecular imaging, he believes two components are of equal importance -- the radiopharmaceutical used for imaging and the scanner instrument that detects it. Given new tracers that are in development coupled with an "explosion on the instrumentation side," he anticipates major advancements in molecular imaging over the next decade.


Equipment enhancements

Faulhaber uses a Philips Medical Systems Gemini PET-CT scanner at the VA affiliate, where they have a large practice in oncology. "We must keep in mind this is a PET scan, providing crucial information, and the CT makes that scan more precise." In particular, he suggests that with patients who have received treatment, being able to assess which portion of a lesion might still be active is vital information to obtain. The 16-slice CT component of the system assists in decreasing scan times from an hour to 24 minutes for a full body study. In the past, PET scans required both a transmission scan for attenuation correction and then an emission scan for the data gathering portion of the study.

Carter S. Young, DO, FACR, chairman and medical director of medical imaging at Methodist Medical Center of Illinois in Peoria reports that with the latest version of the Philips Gemini GXL, he is able to reduce scan times to 18 minutes, down from 50 minutes with their 3D Allegro machine - and all of this with improvements in image quality.

This medical center is a large community hospital that has been using PET since 1991, and currently performs about 1,200 PET scans per year - with 98 percent of them for oncologic indications. They were the first to install the Gemini GXL, which features new detector technology as well as enhanced reconstruction algorithms.

Reduced scan times improve throughput and improve patient comfort.  "To obtain statistically satisfactory data sets requires one to significantly increase the dose of the radiopharmaceutical," explains Young. "It is not unusual for 2D users to decrease their scan times down to 20 to 25 minutes by using 25 milliCuries (mCi) of FDG." Using the GXL and a typical scan time of 18 minutes, they inject 10 to 11 mCi of the FDG radiotracer while producing what he describes as extremely high-quality images.

The significant reduction of radioactive dose required to obtain these studies holds important implications not only for patients, but also for the technologist and other personnel who perform the scans.    

Jacqueline Brunetti, MD, medical director of radiology at Holy Name Hospital in Teaneck, N.J., is using the Discovery LS PET-CT scanner from GE Healthcare to provide radiation therapy planning in addition to the typical scans for diagnosis and staging of cancers. This 4D PET scanner (the fourth dimension relates to motion over time) enables them to perform respiratory-gated PET and CT scans, to use with their gated planning equipment so that they can apply IMRT (intensity modulated radiation therapy) to lung tumors.

By using respiratory-gated radiation, they treat only the active portion of the tumor during a finite portion of the respiratory cycle. In other words, without gating, they would need to treat the tumor throughout its movement pattern during all phases of respiration. However, with the gated technique, treatment occurs only at the end of the expiratory cycle, so they can significantly decrease the size of the field being radiated at point X rather than at points X, Y, and Z where it would naturally shift during normal respiration. 

"The impact for the patient is less radiation damage to the lung, reduced toxicity [lung cancer patients tend to get inflammation of their esophagus], and therefore the ability to complete their full course of radiation," says Brunette. None of the patients treated in this manner have experienced the usual toxicity symptoms.

The other benefit to PET used for lung cancer patients is that they often present with a lesion that obstructs a portion of the airway, and includes a collapsed lung in proximity, reducing the accuracy of other imaging modalities. With PET-CT, they can see exactly where the tumor resides and which portion is metabolically active. 

Imaging tumors in soft tissue, such as the pancreas, stomach and liver have presented challenges because those tumors move with the respiratory cycle. 

"With 4D, you actually get moving pictures of the tumor and location with respiration, so you know how much the tumor is moving," Brunette explains. In some patients, they discover that the tumor hardly moves at all, while others may have a three-centimeter movement pattern. Over the past two years, they have determined that they're able to contour the radiation treatment plan with greater accuracy using these scanning procedures.

R. Edward Coleman, MD, professor and vice chairman of the department of radiology at Duke University Medical Center in Durham, N.C., employs the new GE Healthcare Discovery ST to examine approximately 25 patients per day with 95 percent of the work in oncology. The facility is just beginning to do some cardiac PET imaging coupled with CT angiography, and a small number of patients who require neurological imaging, primarily brain tumor patients, in order to differentiate new tumor lesions from necrosis caused by previous treatment as well as an occasional person with dementia. Coleman anticipates future directions where they could perform cardiac perfusion studies and a CTA simultaneously to determine not only where ischemia is located, but also the cause of the damage.

The Discovery ST, which has reached an installed base of 350 systems worldwide, provides 2D, 3D and 4D imaging capabilities. It is designed to be upgradeable in a cost-effective manner. At the SNM (Society of Nuclear Medicine) meeting this month, GE plans to unveil a new detector geometry for the PET component that is designed to improve spatial resolution while maintaining the system sensitivity, or count rate. They anticipate that will be particularly beneficial as clinicians develop new neurological applications.

Coleman explains that 2D functionality proves helpful for patients who weigh more than 170 pounds. "If one tries to use 3D imaging for large patients, there is so much scatter radiation within the body that degrades the image quality markedly," he says. "However, in the 2D mode, you're collecting the data on an individual slice basis instead of looking at all of the detectors simultaneously in the PET portion of the exam." The implications include improved imaging quality in 2D results.

Robert D. Burke, MD, president of Midtown Imaging LLC in Palm Beach, Fla., is using two biograph16 PET-CT scanners from Siemens for oncologic imaging studies. He finds the scanners have dramatically improved acquisition times, reducing them from a typical hour-long study down to about 15 to 16 minutes. The scanners are primarily used for staging purposes following initial diagnosis as well as for verification of a pulmonary nodule.

"Instead of doing CT guided biopsies, which are invasive, we're able to determine whether or not a nodule is malignant [neoplastic] or benign within a 95 percent positive predictive value range," Burke says. Besides reducing the need to subject patients to further scans or invasive procedures, they are using these scanners to monitor response to chemotherapy.


New tracers on the horizon

Anthony Shields, MD, PhD, professor of medicine at Wayne State University and associate center director at the Barbara Ann Karmanos Cancer Institute in Detroit, is using four dedicated Siemens PET scanners for both clinical and research work, and the facility has ordered the new biograph16 for future applications. This center is highly involved in the development of new radiopharmaceutical tracers.

"FDG [fluorodeoxyglucose] PET is the only approved clinical tracer for oncology, but my research involves other tracers," says Shields. In human trials, they are furthest along with flurothymidine, or FLT, which is used primarily in the assessment of response to therapy, and perhaps diagnostic brain scans. Where FDG reflects glucose metabolism and cellular energetics, FLT reflects cell proliferation.

"I think there will be a wealth of new molecular imaging agents that will be developed and eventually come into clinical use over the next several years," Coleman says.

Initial studies involve fluoro-18 fluorocholine, which is incorporated into cell membranes they have found to be a high-quality imaging agent for prostate cancer. He anticipates further studies with larger numbers of patients. They also are evaluating FLT which he explains looks at DNA synthesis and therefore cell division, so it can be beneficial in studying response to treatment, especially for brain tumors.

While FDG with a half-life of 110 minutes, was the first radiotracer approved by the FDA for use with PET in oncology applications, the development of new imaging agents has proliferated. For example, rubidium-82 (with a half life of 75 seconds) is currently in use for cardiac perfusion studies, while metronidazole labeled with fluorine 18 remains in development for tumor evaluation.


Meanwhile, out in left field

Besides molecular imaging that employs radiopharmacalogic tracers, this field includes other agents used with various modalities such as conventional x-ray, ultrasound or CT.

Kattesh V. Katti, PhD, professor of radiology, professor of physics and senior research scientist at the University of Missouri research reactor in Columbia, Mo., is developing nanoparticles for applications in molecular imaging. The ultimate goal is to produce biocompatible non-toxic agents to be used for imaging cancer and other diseases. They are at the animal testing stage with their research.

"The difference [from molecular imaging with PET and SPECT] is that when you are in the nanoregime, you are close to the size of cells," explains Katti. "This allows you to target individual cells, which means that the ability for clinicians to diagnose certain diseases at the pre-cancerous stage will increase substantially."

Using commercially available gold or silver precursors coupled with a proprietary initiator molecule, and a process occurring entirely in water, they produce the nanoparticles which are attached to certain peptides or proteins that have a high affinity for particular cancer cells.

The potential for nanoparticles moves beyond imaging into the therapy realm. Once a gold-based nanoparticle is attached to a tumor, clinicians will be able to selectively bombard those tumor sites with radiation, and since nanoparticles are metallic, they absorb more of that energy.  Katti believes this functionality is years away, but holds promise for the future.


Conclusion

The combined advances in radiotracers and PET-CT systems have catapulted the field of molecular imaging to improve patient care. Combined hybrid scans provide a level of confidence in guiding tumor biopsies, and in the case of cardiac exams, may decrease the necessity for further testing or invasive procedures through the use of CT angiography combined with PET imaging data.