Nuclear Medicine Used to Evaluate Bone Metastases

NEW YORK—Advances in nuclear medicine may meet the need for more accurate detection and higher-resolution imaging in breast and prostate cancer management, especially in the assessment of bone metastases, speakers said at a symposium on nuclear oncology co-sponsored by Memorial Sloan-Kettering Cancer Center and Johns Hopkins University.

Limitations of Current Prostate Cancer Imaging Techniques

One of the biggest challenges facing prostate cancer treatment is in staging and disease characterization, Peter T. Scardino, MD, chairman of urology, Memorial Sloan-Kettering Cancer Center, said at the nuclear medicine symposium.

“CT scans are not used routinely in prostate cancer and are of no value in men with early-stage disease,” he said, pointing out the futility of searching for positive lymph nodes because they are microscopic in size. “Ultrasound is valuable for guiding needle biopsies but doesn’t describe the extent of the tumor very well,” he added.

Magnetic resonance images are reasonably accurate in detecting local extension, but have limited ability to image cancer within the prostate, Dr. Scardino commented.

Conventional bone scans, he said, yield many false-positive results in patients with PSA levels less than 8 ng/mL, indicating that this type of scan is most useful in patients with a poor prognosis.

Given the diagnostic limitations of the currently available imaging methods, the emerging nuclear medicine techniques may offer help in refining the staging and classification of this complex cancer, he concluded.

The BSI Index

Steven M. Larson, MD, chief of nuclear medicine at Memorial Sloan-Kettering, said that a newly derived bone scan index (BSI) appears useful in predicting bone metastases in prostate cancer patients whose PSA level changes may not accurately reflect their outcomes. Defined as a quantitative estimate of the percent of total skeleton invaded by metastases, the BSI has been shown to correlate with survival time.

In a study of 191 patients with metastatic, hormone-refractory prostate cancer, BSI values less than 4.1% equated with median survival of 18.3 months, whereas BSI values greater than 5.1% correlated with an 8.1 month median survival (P = .0079) (J Clin Oncol 17:948, 1999).

“The utility of the BSI resides in the rationale that cancer treatment is predominantly guided by the stage and extent of the tumor. Less cancer usually equates with a better overall response to treatment,” Dr. Larson said. Thus, any means available to more accurately assess tumor burden in these advanced cancers could markedly improve quality of life and possibly outcome, if treatment is initiated early.

Such timely intervention is key, particularly since the progression of bone involvement by prostate cancer is rapid. Dr. Larson reported that initial BSI doubling times of about 43 days have been observed prior to exponential rises in the index before leveling off. The aggressive nature of such metastatic progression is illustrated in Figure 1.

Dr. Larson also reported preliminary data on the use of positron emission tomography (PET) scanning with ¹⁸F-fluorodeoxyglucose (FDG) and ¹¹C-methionine in a group of 10 prostate cancer patients with high Gleason scores and rapidly increasing PSA levels. Of 82 evaluable bone scan sites, 78% (64) were positive with FDG imaging. Of 13 index lesions, 92% (12) were positive with ¹¹C-methionine scans.

“These PET data are encouraging, but one must note that the lesions studied were heterogeneous and these are advanced cancers. However, the uptake of FDG through increased glycolysis in tumors, and the uptake of labeled methio-nine through increased amino acid transport, can provide information about clinically active sites in bone and soft tissue,” Dr. Larson explained. Importantly, these data suggest that changes in tracer uptake levels may give early evidence of a response to treatment.

Preliminary data for nuclear imaging of breast cancers also appear promising. In a separate presentation, Dr. Larson described initial data focusing on FDG-PET scanning and scintimammography with technetium-99m (Tc 99m) sesta-mibi, a radiolabeled perfusion agent originally indicated for cardiac imaging.

“We have had most of our experience with advanced cancer cases,” Dr. Larson said, explaining that for these cases, the focus has been on refining the differential diagnosis of bone abnormalities, evaluating chest wall and brachial plexus involvement, and, to some degree, looking at treatment responses.

A Recent Study

Dr. Larson said that in a recent study in 10 breast cancer patients with clinical findings suggesting metastates, PET scanning correctly identified metastatic tumors in 9 patients (90%). Moreover, FDG-PET scans were used to confirm the presence of metastases following inconclusive MR scans (Radiology 210:807, 1999).

“FDG-PET scans are useful when intraosseous bone lesions require evaluation to determine benign vs malignant tumors,” Dr. Larson said. He cited a case in which FDG-PET confirmed the absence of bone metastases in a patient whose Tc 99m scan showed strong bony uptake of the isotope, a finding that could imply malignancy (see Figure 2).

SUV Helps Interpretation

“To better interpret FDG-PET scans, an index known as the standardized uptake value, or SUV, is very helpful,” Dr. Larson said. This parameter gives an indication of whether malignancy is present based on the degree of FDG uptake.

SUV ratios are calculated as the ratio of tumor-to-normal-tissue uptake, measured as emitted photon counts and corrected for body weight and injected dose. Normal bone-related SUV values are in the range of about 1.6, whereas an SUV greater than 2 implies a better than 90% chance of malignant bone involvement, he said.

“Importantly, SUV data can correlate with treatment responses in advanced cancer patients,” Dr. Larson added, pointing out that these ratios may reflect the metabolic activity of the tumor itself.