Radiopharmaceuticals Can More Effectively Manage Treatment and Predict Survival for Patients with Gliomas

In the management of gliomas, accurate evaluation of tumor grade and the proliferative activity of cells is key in determining the most appropriate treatment and predicting overall patient survival. Two new studies recently focused on the potential of 3'-deoxy-3'-F-18-fluorothymidine (F-18-FLT) positron emission tomography (PET) imaging to noninvasively and effectively provide tumor-specific data to guide management of patients with gliomas.

Gliomas are atypical neoplasms, and most are diffuse tumors that grow rapidly. Patients with glioblastoma, the most malignant and most frequent type of glioma, typically die within two years. Ensuring the most appropriate treatment in a timely manner is of utmost importance for these patients.

Two studies published in the December 2012 issue of the Journal of Nuclear Medicine (JNM) examined the utility of F-18-FLT PET for providing prognostic information for patients with gliomas. “The accumulation of F-18-FLT is dependent on the presence of thymidine kinase-1, which is closely linked with cellular proliferation. In several clinical studies, F-18-FLT has been validated for evaluation of tumor grade and cellular proliferation in gliomas,” noted Yuka Yamamoto, MD, from the department of radiology, Faculty of Medicine, Kagawa University (Kagawa, Japan;), and lead author of the study.

Investigators retrospectively evaluated F-18-FLT uptake in patients with newly diagnosed (36 patients) and recurrent (20 patients) gliomas. Patients underwent F-18-FLT PET scanning; tissue specimens were then taken to obtain a pathologic diagnosis. The F-18-FLT images were analyzed by two nuclear medicine physicians, who identified tumor lesions as areas of focally increased uptake exceeding that of normal brain background, and who determined the tumor-to-normal (T/N) ratio. Results the 18-F-FLT PET scan were compared with tumor grade and proliferative activity estimated from the tissue specimens.

Researchers found that there was considerable difference in the T/N ratio among different grades of newly diagnosed and recurrent gliomas. F-18-FLT uptake correlated more strongly with the proliferative activity in newly diagnosed gliomas than in recurrent gliomas and provided a more comprehensive view to determine tumor grade as compared to a single tissue specimen.

The correlation between proliferative volume and prediction of overall survival for high-grade glioma patients was also explored. In the study, 26 consecutive patients underwent preoperative 18-F-FLT PET/computed tomography (CT) scans. The maximum standardized uptake value (SUVmax) was calculated and three different PET segmentation methods were used to estimate the proliferative volume. The prognostic value of the SUVmax and the different methods to approximate proliferative volume for overall survival were then assessed.

The mean overall survival for the patients in the study was 397 days; 19 patients died during this time. Based on this follow-up information, researchers determined that the signal-to-background ration (SBR) for an adaptive threshold delineation (PVSBR) technique demonstrated a considerably better association with overall survival then the SUVmaxor the other two PET segmentation methods.

“The predictive value of the proliferative volume for the overall survival of patients seems to be independent of the postoperative treatment,” explained Albert J.S. Idema, MD, from the department of neurosurgery, Radboud University Nijmegen Medical Center (Nijmegen, The Netherlands), and lead author of the study. “The importance for patients is the possible utilization of 18-F-FLT PET to select the most appropriate treatment options. The very limited burden that the procedure causes to the patient is a further asset.”

The development of new molecular imaging agents, such as F-18-FLT, which is now used only for research purposes, has enabled clinical researchers to utilize the agents to evaluate the features of tumors and their therapeutic response. “We hope that these findings will be helpful for identifying the role of F-18-FLT in assessing the response to antiproliferative treatment in patients with gliomas,” said Dr. Yamamoto.

Related Links:
Kagawa University
Radboud University