title: Usefulness of [18F]-DA and [18F]-DOPA for PET imaging in a mouse model of pheochromocytoma.
abstract: OBJECTIVE
  To evaluate the usefulness of [(18)F]-6-fluorodopamine ([(18)F]-DA) and [(18)F]-L-6-fluoro-3,4-dihydroxyphenylalanine ([(18)F]-DOPA) positron emission tomography (PET) in the detection of subcutaneous (s.c.) and metastatic pheochromocytoma in mice; to assess the expression of the norepinephrine transporter (NET) and vesicular monoamine transporters 1 and 2 (VMAT1 and VMAT2), all important for [(18)F]-DA and [(18)F]-DOPA uptake. Furthermore, to compare tumor detection by micro-computed tomography (microCT) to magnetic resonance imaging (MRI) in individual mouse.
  
  
  METHODS
  SUV(max) values were calculated from [(18)F]-DA and [(18)F]-DOPA PET, tumor-to-liver ratios (TLR) were obtained and expression of NET, VMAT1 and VMAT2 was evaluated.
  
  
  RESULTS
  [(18)F]-DA detected less metastatic lesions compared to [(18)F]-DOPA. TLR values for liver metastases were 2.26-2.71 for [(18)F]-DOPA and 1.83-2.83 for [(18)F]-DA. A limited uptake of [(18)F]-DA was found in s.c. tumors (TLR = 0.22-0.27) compared to [(18)F]-DOPA (TLR = 1.56-2.24). Overall, NET and VMAT2 were expressed in all organ and s.c. tumors. However, s.c. tumors lacked expression of VMAT1. We confirmed [(18)F]-DA's high affinity for the NET for its uptake and VMAT1 and VMAT2 for its storage and retention in pheochromocytoma cell vesicles. In contrast, [(18)F]-DOPA was found to utilize only VMAT2.
  
  
  CONCLUSIONS
  MRI was superior in the detection of all organ tumors compared to microCT and PET. [(18)F]-DOPA had overall better sensitivity than [(18)F]-DA for the detection of metastases. Subcutaneous tumors were localized only with [(18)F]-DOPA, a finding that may reflect differences in expression of VMAT1 and VMAT2, perhaps similar to some patients with pheochromocytoma where [(18)F]-DOPA provides better visualization of lesions than [(18)F]-DA.
authors.affiliation: Program in Reproductive and Adult Endocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD 20892-1109, USA.
authors.forename: Lucia
authors.initials: L
authors.lastname: Martiniova
authors.forename: Susannah
authors.initials: S
authors.lastname: Cleary
authors.forename: Edwin W
authors.initials: EW
authors.lastname: Lai
authors.forename: Dale O
authors.initials: DO
authors.lastname: Kiesewetter
authors.forename: Jurgen
authors.initials: J
authors.lastname: Seidel
authors.forename: Linda F
authors.initials: LF
authors.lastname: Dawson
authors.forename: Jacqueline K
authors.initials: JK
authors.lastname: Phillips
authors.forename: David
authors.initials: D
authors.lastname: Thomasson
authors.forename: Xiaoyuan
authors.initials: X
authors.lastname: Chen
authors.forename: Graeme
authors.initials: G
authors.lastname: Eisenhofer
authors.forename: James F
authors.initials: JF
authors.lastname: Powers
authors.forename: Richard
authors.initials: R
authors.lastname: Kvetnansky
authors.forename: Karel
authors.initials: K
authors.lastname: Pacak
mesh_terms: D000310:Adrenal Gland Neoplasms / Q000175:diagnosis / Q000000981:diagnostic imaging*; D000818:Animals; D003287:Contrast Media / Q000493:pharmacokinetics; D004295:Dihydroxyphenylalanine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D004298:Dopamine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D005260:Female; D008113:Liver Neoplasms / Q000175:diagnosis / Q000556:secondary; D008175:Lung Neoplasms / Q000175:diagnosis / Q000556:secondary; D008279:Magnetic Resonance Imaging / Q000379:methods; D051379:Mice; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis / Q000556:secondary; D009374:Neoplasms, Experimental / Q000175:diagnosis / Q000556:secondary; D050484:Norepinephrine Plasma Membrane Transport Proteins / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000175:diagnosis / Q000556:secondary; D010673:Pheochromocytoma / Q000175:diagnosis / Q000000981:diagnostic imaging* / Q000556:secondary; D049268:Positron-Emission Tomography / Q000379:methods*; D012680:Sensitivity and Specificity; D014057:Tomography, X-Ray Computed / Q000379:methods; D050493:Vesicular Monoamine Transport Proteins / Q000378:metabolism
chemical_list: D003287:Contrast Media; D050484:Norepinephrine Plasma Membrane Transport Proteins; D050493:Vesicular Monoamine Transport Proteins; C043437:fluorodopa F 18; C029253:6-fluorodopamine; D004295:Dihydroxyphenylalanine; D004298:Dopamine