title: 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.
abstract: 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'-18F-fluorothymidine (18F-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 investigate18F-FLT PET as a prognostic marker for NENs in comparison with18F-FDG PET and Ki-67 index.
  
  
  METHODS
  One hundred patients were PET-scanned with both18F-FLT and18F-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 and18F-FLT uptake was also investigated.
  
  
  RESULTS
  Thirty-seven percent of patients had a positive18F-FLT PET scan, and 49% had18F-FDG PET-positive foci. Patients with a high18F-FLT uptake had a significantly shorter OS and PFS than patients with low or no18F-FLT uptake. No correlation was found between Ki-67 index and18F-FLT uptake. In a multivariate analysis18F-FLT,18F-FDG, and Ki-67 all were significant prognostic markers of PFS. For OS, only18F-FDG and Ki-67 remained significant.
  
  
  CONCLUSIONS
  18F-FLT PET has prognostic value in NEN patients but when18F-FDG PET and Ki-67 index are also available, a multivariate model revealed that18F-FLT PET only adds information regarding PFS but not OS, whereas18F-FDG PET remains predictive of both PFS and OS. However, a clinically robust algorithm including18F-FLT in addition to18F-FDG and Ki-67 could not be found. Accordingly, the exact role, if any, of18F-FLT PET in NENs remains to be established.
authors.affiliation: Department of Clinical Physiology, Nuclear Medicine & PET and Cluster for Molecular Imaging, Rigshospitalet and University of Copenhagen, Cophenhagen, Denmark.|ENETS Neuroendocrine Tumor Center of Excellence, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Camilla B
authors.initials: CB
authors.lastname: Johnbeck
authors.affiliation: ENETS Neuroendocrine Tumor Center of Excellence, Rigshospitalet, Copenhagen, Denmark.|Department of Surgical Gastroenterology and Department of Clinical Endocrinology, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Knigge
authors.affiliation: ENETS Neuroendocrine Tumor Center of Excellence, Rigshospitalet, Copenhagen, Denmark.|Department of Oncology, Rigshospitalet, Copenhagen, Denmark; and.
authors.forename: Seppo W
authors.initials: SW
authors.lastname: Langer
authors.affiliation: Department of Clinical Physiology, Nuclear Medicine & PET and Cluster for Molecular Imaging, Rigshospitalet and University of Copenhagen, Cophenhagen, Denmark.|ENETS Neuroendocrine Tumor Center of Excellence, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Annika
authors.initials: A
authors.lastname: Loft
authors.affiliation: Department of Clinical Physiology, Nuclear Medicine & PET and Cluster for Molecular Imaging, Rigshospitalet and University of Copenhagen, Cophenhagen, Denmark.|ENETS Neuroendocrine Tumor Center of Excellence, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Anne Kiil
authors.initials: AK
authors.lastname: Berthelsen
authors.affiliation: ENETS Neuroendocrine Tumor Center of Excellence, Rigshospitalet, Copenhagen, Denmark.|Department of Pathology, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Birgitte
authors.initials: B
authors.lastname: Federspiel
authors.affiliation: Department of Clinical Physiology, Nuclear Medicine & PET and Cluster for Molecular Imaging, Rigshospitalet and University of Copenhagen, Cophenhagen, Denmark.|ENETS Neuroendocrine Tumor Center of Excellence, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Tina
authors.initials: T
authors.lastname: Binderup
authors.affiliation: Department of Clinical Physiology, Nuclear Medicine & PET and Cluster for Molecular Imaging, Rigshospitalet and University of Copenhagen, Cophenhagen, Denmark akjaer@sund.ku.dk.|ENETS Neuroendocrine Tumor Center of Excellence, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Andreas
authors.initials: A
authors.lastname: Kjaer
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism; D015224:Dideoxynucleosides; D018572:Disease-Free Survival; D005260:Female; D019788:Fluorodeoxyglucose F18; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D018358:Neuroendocrine Tumors / Q000000981:diagnostic imaging* / Q000378:metabolism*; D049268:Positron-Emission Tomography
chemical_list: D014408:Biomarkers, Tumor; D015224:Dideoxynucleosides; D019394:Ki-67 Antigen; D019788:Fluorodeoxyglucose F18; C002854:alovudine
keywords: 18F-FDG PET; 18F-FLT PET; Ki67; neuroendocrine neoplasms; prognosis