FLT-PET Imaging Superior to Bone-Marrow Biopsy for Assessing Treatment Response in Leukemia

Roxanne Nelson

August 04, 2008

August 4, 2008 — In patients with hematopoietic diseases, assessment for an early response to chemotherapy may be feasible with 18F fluorothymidine–positron emission tomography (FLT-PET), reported researchers at the 50th annual meeting of the American Association of Physicists in Medicine.

Almost one-third of all patients with leukemia do not respond to treatment, but that is usually not apparent until they have undergone a full week of chemotherapy and then waited a month to evaluate their response. In this study, researchers found that FLT-PET scans may be able to assess patient response after only 1 day of chemotherapy.

Using PET scans to determine treatment response in cancer patients is not entirely new, explained the study's primary investigator, Robert Jeraj, PhD, an assistant professor in the departments of medical physics, human oncology, and biomedical engineering at the University of Wisconsin, in Madison.

"FLT-PET has been previously used to assess response in patients treated with chemotherapy, although not extensively and typically in smaller cohorts of patients," he said.

Assessing for response in patients with hematopoietic diseases such as leukemia is essential for appropriate and effective management. A bone-marrow biopsy is routinely performed following chemotherapy, but this is an invasive procedure and an ineffective predictor of treatment response. Based on their preliminary data, FLT-PET appears to be superior to bone-marrow biopsy in determining early responders to chemotherapy among patients with leukemia, noted Dr. Jeraj.

However, he cautions that this study is only a pilot trial, and results are based on a very limited set of patients. "A more extensive study on a larger cohort of patients would be necessary to confirm the hypothesis," he told Medscape Oncology.

In this study, Dr. Jeraj and colleagues developed a molecular imaging–based methodology for bone-marrow assessment and hypothesized that it may be able to assess an early treatment response in adult leukemia patients.

The study cohort consisted of 6 patients with leukemia and 10 controls with normal bone marrow. All of the 16 participants were injected with 5-mCi 18F-FLT, which is a marker of cellular proliferation, and also received whole-body PET/computed tomography (CT) scans. The leukemia patients then received standard induction chemotherapy and were imaged at progressively earlier time points during therapy.

The researchers used normal bone marrow to establish baseline assessment parameters that included bone-marrow mean standardized uptake values (SUV), SUV distribution, and heterogeneity of the axial distribution of bone-marrow uptake from the pelvis to neck. They evaluated the bone marrow from the leukemia patients, and then responders to therapy were compared with nonresponders.

Their results showed that the mean bone-marrow SUV of responders to chemotherapy was lower than that of nonresponders (0.76 ± 0.05 vs 1.60 ± 0.14; P = .0054). Among patients who responded to therapy, the SUV distribution showed a dramatic shift toward lower SUVs, as compared with the controls. This shift was considerably smaller among nonresponding patients.

They also observed that the axial distribution of bone-marrow uptake was more heterogeneous in nonresponders, as compared with responders, and this heterogeneity might be able to explain the poor predictive power of the bone-marrow biopsy. The time of assessment did not significantly affect the measurement of treatment response.

Scanning could be routinely performed in this patient population, although FLT-PET imaging is currently available only in certain larger centers, as it is limited by accessibility to the FLT tracer, Dr. Jeraj pointed out. "FLT will be commercially available to all the clinics in the near future, and it is already available in some parts of the country. Once FLT becomes commercially available and used more frequently, the expenses will be comparable to those of [18F fluorodeoxyglucose] FDG-PET scans."

Currently the costs are approximately $1000 to $1500 higher as compared with FDG-PET. "Still, these are rather negligible costs given the potential benefits to the patients," he added.

The researchers concluded that given the limitations of bone-marrow biopsy, FLT-PET imaging might be a superior tool for assessing treatment response in patients with hematopoietic diseases.

If proven successful and if it shows high sensitivity and specificity in a larger study, Dr. Jeraj believes that FLT-PET for assessment of leukemia patients will definitely be routinely utilized. "Similarly, FLT-PET imaging will most likely be used for assessment of other types of cancer therapies."

American Association of Physicists in Medicine: Abstract 8912. Presented July 31, 2008.


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