Abstract
This is the first in-man clinical study of 18F-fludarabine which is a radiopharmaceutical for PET imaging in lymphoma where many issues remain controversial with the standard radiotracer 18F-FDG.
Methods: 18F-Fludarabine-PET(/CT) was performed in 10 patients: five with diffuse large B-cell lymphoma (DLBCL) and five with chronic lymphocytic leukemia (CLL). The biodistribution, and radiation dosimetry of 18F-fludarabine have also been evaluated. Six successive partial body PET scans were acquired for 250 min after intravenous 4 MBq/kg bolus of 18F-fludarabine. Standardized uptake values (SUVs) were recorded in each involved lymph node territory and for several extranodal sites, with particular reference to the liver. In order to assess the time-related uptake profile of 18F-fludarabine, PET images were analyzed by delineating volumes of interest (VOIs) over the uptake sites on the most optimal scan for visual observation and projected onto all co-registered scans of the same subject. Physical examination, laboratory studies and contrast-enhanced CT were performed in all patients. For the DLBCL group, 18F-FDG-PET was also considered.
Results: In DLBCL patients, increased 18F-fludarabine uptake was observed in sites considered abnormal by CT and/or 18F-FDG, with SUVs significantly higher in involved lesions in comparison with physiological non-target sites. Nonetheless, the comparison of 18F-fludarabine- and 18F-FDG-PET showed discrepancies in two patients. In CLL patients, the uptake of 18F-fludarabine coincided with sites expected to be involved, including splenic invasion, according to conventional clinical and CT staging and displayed a significant uptake in hematopoietic bone marrow. No uptake was observed, whatever the disease group, in the cardiac muscle and brain. The mean effective dose from a mean injected 18F-fludarabine activity of 305 ± 76 MBq was 3.07 ± 0.81 mSv.
Conclusion: 18F-Fludarabine-PET might well be a promising tool for lymphoproliferative diseases. The radiation dose of this radiopharmaceutical is below that of the 18F-FDG. The specificity of this novel PET probe for lymphoid cells, its absence of accumulation in reactive tissues, as well as its feasibility for detection of bone marrow infiltration could play an innovative role in lymphoma imaging.
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