Prognostic Value of 18F-FLT PET in Patients with Neuroendocrine Neoplasms: A Prospective Head-to-Head Comparison with 18F-FDG PET and Ki-67 in 100 Patients

Neuroendocrine neoplasms (NENs) constitute a heterogeneous group of tumors arising in various organs and with a large span of aggressiveness and survival rates. The Ki-67 proliferation index is presently used as the key marker of prognosis, and treatment guidelines are largely based on this index. 3'-deoxy-3'-F-18-fluorothymidine (F-18-FLT) is a proliferation tracer for PET imaging valuable in the monitoring of disease progression and treatment response in various types of cancer. However, until now only data from 10 patients with NEN were available in the literature. The aim of the present study was to investigate F-18-FLT PET as a prognostic marker for NENs in comparison with F-18-FDG PET and Ki-67 index. Methods: One hundred patients were PET-scanned, with both F-18-FLT and F-18-FDG within the same week, and the prognostic value of a positive scan was examined in terms of progression-free survival (PFS) and overall survival (OS). The correlation between the Ki-67 index and F-18-FLT uptake was also investigated. Results: Thirty-seven percent of patients had a positive F-18-FLT PET scan, and 49% had F-18-FDG PET-positive foci. Patients with a high F-18-FLT uptake had a significantly shorter OS and PFS than patients with low or no F-18-FLT uptake. No correlation was found between Ki-67 index and F-18-FLT uptake. In a multivariate analysis F-18-FLT, F-18-FDG, and Ki-67 all were significant prognostic markers of PFS. For OS, only F-18-FDG and Ki-67 remained significant. Conclusion: F-18-FLT PET has prognostic value in NEN patients but when F-18-FDG PET and Ki-67 index are also available, a multivariate model revealed that 18F-FLT PET only adds information regarding PFS but not OS, whereas F-18-FDG PET remains predictive of both PFS and OS. However, a clinically robust algorithm including F-18-FLT in addition to F-18-FDG and Ki-67 could not be found. Accordingly, the exact role, if any, of F-18-FLT PET in NENs remains to be established.