title: 18F-FLT PET/CT in the Evaluation of Pheochromocytomas and Paragangliomas: A Pilot Study.
abstract: (18)F-FDG PET/CT has been proven to be a highly sensitive method for pheochromocytomas/paragangliomas (PHEOs/PGLs) associated with succinate dehydrogenase (SDH) mutations. This finding has been attributed to altered tumor cell metabolism resulting from these mutations and does not provide additional prognostic information to genotype. Therefore, identification of new biomarkers for aggressiveness is needed. A high Ki-67 index was proposed to be an additional prognostic factor. This pilot study aimed to evaluate 3'-deoxy-3'-(18)F-fluorothymidine ((18)F-FLT) PET/CT, a PET proliferation tracer, as a potential imaging agent in a series of 12 PHEO/PGL patients with different genetic backgrounds, to compare (18)F-FLT uptake with (18)F-FDG PET/CT, and to evaluate classic factors of aggressiveness.
  
  
  METHODS
  Twelve patients (7 metastatic and 5 nonmetastatic) were prospectively evaluated with (18)F-FDG and (18)F-FLT and followed for at least 2 y after the initial imaging work-up. Uptake was assessed at a lesion level, visually and quantitatively by maximum standardized uptake values (SUVmax) for both tracers. (18)F-FLT uptake was compared with risk factors known to be linked with a poor prognosis in PGLs (SDHB-mutated status, lesion size, dopaminergic phenotype) and with (18)F-FDG uptake.
  
  
  RESULTS
  In 12 patients, 77 lesions were assessed. All lesions had low (18)F-FLT uptake (median SUVmax, 2.25; range, 0.7-4.5). There was no apparent superiority of (18)F-FLT uptake in progressive lesions, and most of the lesions showed a mismatch, with high (18)F-FDG uptake (median SUVmax, 10.8; range, 1.1-79.0) contrasting with low (18)F-FLT uptake.
  
  
  CONCLUSIONS
  This study suggests that PHEOs/PGLs-even those that progress-do not exhibit intense (18)F-FLT uptake. It provides the first in vivo demonstration that proliferation may not be a major determinant of (18)F-FDG uptake in these tumors. These findings provide new insight into the biologic behavior of PGL and suggest that antiproliferative agents may be suboptimal for treatment of these tumors.
authors.affiliation: Program in Reproductive and Adult Endocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health, Bethesda, Maryland.
authors.forename: Elise M
authors.initials: EM
authors.lastname: Blanchet
authors.affiliation: La Timone University Hospital, European Center for Research in Medical Imaging, Aix-Marseille University, Marseille, France.
authors.forename: David
authors.initials: D
authors.lastname: Taieb
authors.affiliation: Positron Emission Tomography Department, Warren Grant Magnuson Clinical Center, National Institutes of Health, Bethesda, Maryland.
authors.forename: Corina
authors.initials: C
authors.lastname: Millo
authors.affiliation: Program in Reproductive and Adult Endocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health, Bethesda, Maryland.
authors.forename: Victoria
authors.initials: V
authors.lastname: Martucci
authors.affiliation: Nuclear Medicine Department, Warren Grant Magnuson Clinical Center, National Institutes of Health, Bethesda, Maryland; and.
authors.forename: Clara C
authors.initials: CC
authors.lastname: Chen
authors.affiliation: Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Maria
authors.initials: M
authors.lastname: Merino
authors.affiliation: Positron Emission Tomography Department, Warren Grant Magnuson Clinical Center, National Institutes of Health, Bethesda, Maryland.
authors.forename: Peter
authors.initials: P
authors.lastname: Herscovitch
authors.affiliation: Program in Reproductive and Adult Endocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health, Bethesda, Maryland karel@mail.nih.gov.
authors.forename: Karel
authors.initials: K
authors.lastname: Pacak
mesh_terms: D000310:Adrenal Gland Neoplasms / Q000000981:diagnostic imaging* / Q000235:genetics / Q000473:pathology; D000328:Adult; D000368:Aged; D049109:Cell Proliferation; D015224:Dideoxynucleosides; D004298:Dopamine; D005260:Female; D005820:Genetic Testing; D006019:Glycolysis; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008297:Male; D008875:Middle Aged; D010235:Paraganglioma / Q000000981:diagnostic imaging* / Q000235:genetics; D010673:Pheochromocytoma / Q000000981:diagnostic imaging* / Q000235:genetics / Q000473:pathology; D010865:Pilot Projects; D049268:Positron-Emission Tomography / Q000379:methods*; D011379:Prognosis; D019275:Radiopharmaceuticals; D012015:Reference Standards; D012307:Risk Factors; D051598:Whole Body Imaging
chemical_list: D015224:Dideoxynucleosides; D019275:Radiopharmaceuticals; C002854:alovudine; D004298:Dopamine
keywords: 18F-fluorodeoxyglucose; 18F-fluorothymidine; glycolysis; pheochromocytoma and paraganglioma; positron emission tomography; proliferation