Charles Bankhead

Cardiologists impressed by the diagnostic power of PET/CT are beginning to recognize its clinical importance. In sites where the transition from PET to PET/CT has been made, rising cardiac PET imaging volumes have followed. Although the promise of improved cancer imaging originally led radiologists at Brigham and Women's Hospital in Boston to acquire their first PET/ CT scanner, the ability to fuse functional PET with anatomically detailed CT and CT angiography images has gained the support of cardiologists as well.

"We have seen a rapid conversion from PET to PET/CT because of applications in oncology. As a result, PET/CT use has grown along with cardiac imaging," said Dr. Marcelo DiCarli, director of cardiovascular imaging at Brigham and Women's.

Once exclusively the domain of academic practitioners, cardiac PET/CT is winning over more community-based physicians. Dr. Randy Patterson, a nuclear cardiologist at Emory Crawford Long Hospital in Atlanta, estimates that half of the patients referred for cardiac PET imaging at his outpatient clinic originate from private-practice physicians. Cardiac PET/CT imaging volume at Emory's affiliated hospitals and clinics is expected to reach 3300 cases in 2006.

"The images are so much easier to interpret than SPECT," Patterson said. "You can feel so much more confident in what you're seeing."

Although cardiac PET/CT is still considerably more expensive than thallium-201 or technetium-99m MIBI SPECT, threatened cuts in PET/CT reimbursement actually promise to increase its popularity, said Dr. Rory Hachamovitch, a cardiologist and visiting associate professor of clinical medicine at the University of Southern California.

The introduction of more flexible contracts for rubidium generators has made cardiac PET/CT more practical. Facilities can now contract for weekly or biweekly access, instead of mandatory access throughout the entire month, DiCarli said. Brigham and Women's Hospital is billed by the unit dose, although it still has full-time access to a rubidium generator.

"PET/CT is what MR claimed to be for years but wasn't-the one-stop shop for imaging," Hachamovitch said. "We haven't heard more about it because PET has often been the domain of nuclear medicine and radiology. It is only now that cardiologists are becoming aware that it exists and that they can use it for many of their patients."

Perfusion PET assesses myocardial function, while CTA covers coronary anatomy. CT also simultaneously provides PET attenuation correction and captures imaging data for calcium scoring.

"It offers the whole gamut of atherosclerosis and coronary assessment and ischemia assessment and functional assessment, all in one package," he said.

Radiologists and cardiologists have begun to recognize that PET offers superior results over other options for morbidly obese patients. PET/CT's ability to accommodate patients weighing up to 450 pounds has led to a flood of new cardiac imaging PET/CT orders at Emory University, Patterson said.

"For obese patients, you get a better image with PET than you ever would with SPECT," he said.

PET/CT is especially useful after an equivocal or nondiagnostic SPECT study, Patterson said. Emergency room physicians are increasingly ordering it for chest pain patients who have a moderate risk of myocardial infarction. The studies allow them to rule out MI with greater confidence, thereby avoiding unnecessary hospital admissions.

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Cardiologists impressed by the diagnostic power of PET/CT are beginning to recognize its clinical importance. In sites where the transition from PET to PET/CT has been made, rising cardiac PET imaging volumes have followed.

Cardiac PET/CT gains clinical recognition

Molecular imaging will figure prominently in collaborations among public and private interests to modernize the drug development process and make new therapies available more quickly and at lower cost.

In March, the Critical Path Initiative, an FDA program created to refine the development process for medical products, released its initial priority list of projects. The list includes 76 projects. Nine of these involve use of modern imaging techniques to advance translational research. One of the nine imaging-related research priorities focuses on cancer applications. One of the first investigations within that priority will examine the ability of FDG-PET imaging to predict response to therapy in lymphoma patients. Persistent FDG uptake might identify patients with unresponsive disease early in their treatment and enable a switch to other more effective therapies.

Speaking at the Academy of Molecular Imaging meeting in March, Dr. Sandra Horning, president of the American College of Clinical Oncology, made note of the predictive value of PET scanning performed in the middle of treatment for non-Hodgkin's lymphoma (NHL). Cumulative data from multiple sources suggest PET imaging has prognostic value after as few as one or two cycles of therapy, reflected in a positive predictive value of 100% and a negative predictive value of 84%, she said.

While encouraging, the data offer no proof that switching from one therapy to another on the basis of PET imaging will improve patient outcomes.

"We need a randomized study in which PET-positive patients are assigned to continue with conventional therapy or cross over to a different treatment," she said.

The Eastern Cooperative Oncology Group based in Boston and Philadelphia has just begun such a trial. Patients will have PET scans after three cycles of rituximab-CHOP chemoimmunotherapy. Those with negative scans will continue treatment, while patients with positive scans will be switched to another therapy.

Several recent studies show that FDG-PET, whether performed at the end of therapy or in midcourse, can identify lymphoma patients whose disease is not responding to treatment. Belgian investigators examined the ability of end-of-treatment FDG-PET to predict relapse (J Clin Oncol 2001; 19:414-419). Of 67 patients who had normal PET scans after completion of initial chemotherapy, 56 remained in complete remission during median follow-up of 653 days. By contrast, 26 patients had persistent abnormal FDG uptake, and all relapsed. In 14 of the 26 patients, only PET imaging predicted the presence of persistent disease.

A study from the University of Iowa examined the impact of adding FDG-PET results to the International Workshop Criteria (IWC) for classification of treatment response (J Clin Oncol 2005;23:4652-4661). The study involved 54 patients with aggressive NHL treated with four to eight cycles of chemotherapy. FDG-PET imaging was performed one to 16 weeks after completion of therapy. Comparison of IWC alone and IWC with FDG-PET showed that the addition of PET led to a more accurate response classification.

More recently, clinical investigators have explored the ability of FDG-PET imaging to predict response to therapy before the end of the treatment. A group at Guy's and St. Thomas's Hospital in London performed FDG-PET studies after two or three cycles of chemotherapy in 121 patients with high-grade NHL (Ann Oncol 2005;16:1514-1523). Fifty patients had negative scans, 19 had minimal residual uptake (MRU) of FDG, and 52 had positive scans. Estimates of five-year survival correlated with PET results: 88.8% for the PET-negative patients, 59.3% for patients with MRU, and 16.2% for PET-positive patients.

Finally, a group at Memorial Sloan-Kettering Cancer Center in New York City evaluated the intensity of FDG uptake as a means of distinguishing between indolent and aggressive NHL (J Clin Oncol 2005;23:4643-4651). The results of FDG-PET studies in 97 patients showed that a standardized uptake value greater than 10 was associated with a high likelihood of aggressive disease.

In an accompanying editorial, Dr. Malik Juweid, a radiologist at the University of Iowa, and Dr. Bruce Cheson, an oncologist at Georgetown University, said more research is needed to determine the prognostic value of FDG-PET imaging in NHL. Juweid and Cheson noted, however, that the role of PET for monitoring tumor response is likely to increase once clinical trials demonstrate that information provided by PET imaging affects patient management and outcomes.

MI blazes critical path to speedy assessments

PET/CT imaging has evolved in the past five years from an undefined new technology to an invaluable instrument that provides critical information for clinical decision making.

PET/CT has built its reputation primarily in oncology applications, which represent the majority of approved indications. The hybrid technique's impact has been greatest in diagnosis, evaluation, and management of non-small cell lung cancer (NSCLC). A study published last year showed that PET imaging of patients in a university-based lung cancer practice changed clinical management in more than 70% of cases (Chest 2005;128:698-703).

The impact has been almost as dramatic in the community hospital setting.

"We're just now collecting data in the lung cancer clinic, but I suspect that our findings will be similar [to those from the university-based study]," said Dr. Robert Jotte, medical director of the Lung Cancer Clinic of the Rockies in Denver. "I suspect the data will show that PET/CT changes clinical management in at least 50% of our cases."

The center has two mobile PET/CT scanners and has phased out use of its PET-only device. Between 80 and 90 patients arrive at the clinic each week. Most have a PET/CT study at some point in their clinical management.

PET/CT plays a role in evaluating patients with all stages of NSCLC. For those with stage 1 or stage 2 disease, PET/CT is used to rule out metastatic disease and determine whether patients are candidates for surgical resection. With stage 3 NSCLC, PET/CT studies focus on lymph node involvement; extent will determine appropriate therapy. For patients with stage 4 NSCLC, the test helps avoid unnecessary procedures and treatment when the primary clinical consideration is quality of life.

The ability to superimpose a CT image over a PET scan represents a major advance over the two individual imaging modalities, Jotte said. As an example, patients with stage 3 lung cancer frequently present with an obstructive airway lesion that causes collapse of the lung behind the lesion. Prior to PET/CT, clinicians were obligated to treat the lesion and the collapsed but normal lung tissue with radiation because the border between normal and malignant tissue could not be distinguished easily.

"Fused images will show increased glucose uptake in the tumor, and we can define where the tumor, stops and the normal collapsed lung begins," Jotte said.

At Radiology Associates of Tarrant County in Fort Worth, three or four lung cancer patients a day have PET/CT scans, including patients with single pulmonary nodules (SPN) and those diagnosed with lung cancer. Characterization of SPN was one of the first approved indications for PET and remains one of the most common applications of the hybrid technique.

PET/CT is used routinely to stage NSCLC patients, said Dr. Paul Shyn, a radiologist with the Fort Worth group. PET/CT guides treatment, particularly when it comes to making decisions about a patient's surgical candidacy. Radiation oncologists rely heavily on PET/CT images to develop their treatment protocols.

"The more precisely we can stage a patient, the more helpful we can be to the patient," Shyn said. "It seems that PET/CT is the most accurate way of doing that."

The expanding role of PET/CT in managing NSCLC patients is illustrated by the early experience of radiologists at Virginia Oncology Associates in Norfolk. When the organization launched its PET/CT service in April 2005, 21 NSCLC patients had scans during the first month of operation. The daily volume of lung cancer patients more than doubled over the next 12 months to 43 scans per month by April 2006.

"I think physicians like PET/CT imaging because it is one study that provides a very good way of looking for evidence of metastatic disease," said Dr. Paul Conkling, director of the early-phase research program at the Virginia facility. "In the initial staging, if an abnormality in the mediastinum is seen on both PET and CT, that's very powerful evidence of a positive node, and that may alter treatment plans. Instead of taking the patient straight to surgery, we might prefer to treat with chemotherapy or some other form of therapy first."

Because of its ability to identify disease in the center of the chest, PET/CT will probably help fuel the trend toward increased use of neoadjuvant chemotherapy in NSCLC, Conkling said. Patients with such centrally located lesions often receive a course of chemotherapy in an effort to downstage the disease and help the patient qualify for surgical resection. With the advent of PET/CT staging of NSCLC, more patients might become resectable.

Charles Bankhead

Articles

Cardiac PET/CT gains clinical recognition

Cardiac PET/CT gains clinical recognition

MI blazes critical path to speedy assessments

FDG-PET/CT asserts itself for lung cancer imaging