title: Small-animal PET with a σ-ligand, 11C-SA4503, detects spontaneous pituitary tumors in aged rats.
abstract: Pituitary tumors are often detected only after death or at late stages of the disease when they are macroadenomas with a low surgical cure rate. Spontaneous pituitary tumors occur in rats over 1 y of age. In an ongoing study of changes in σ-1 agonist binding related to aging, several of our rats developed such tumors. The aim of the current study was to assess the kinetics of (11)C-SA4503 ((11)C-labeled 1-[2-(3,4-dimethoxyphenthyl)]-4-(3-phenylpropyl)-piperazine dihydrochloride) in tumor and brain and to evaluate the utility of this tracer in the detection of pituitary tumors.
  
  
  METHODS
  Small-animal PET scans of the brain region of male Wistar Hannover rats (age, 18-32 mo) were acquired using the σ-1 agonist tracer (11)C-SA4503. The time-dependent uptake of (11)C in the entire brain, tumor or normal pituitary, and thyroid was measured. A 2-tissue-compartment model was fitted to the PET data, using metabolite-corrected plasma radioactivity as the input function.
  
  
  RESULTS
  Pituitary tumors showed up as bright hot spots in the scans. The total distribution volume (VT) of the tracer was significantly higher in the tumor than in the normal pituitary. Surprisingly, a higher VT was also seen in the brain and thyroid tissue of animals with pituitary tumors than in healthy rats. The increase in VT in the brain and thyroid was not related to a change in nondisplaceable binding potential (BPND) but rather to an increase in the partition coefficient (K1/k2) of (11)C-SA4503. The increase in VT in the tumor on the other hand was accompanied by a significant increase in BPND. Western blotting analysis indicated that pituitary tumors overexpressed σ-1 receptors.
  
  
  CONCLUSIONS
  The overexpression of σ-1 receptors in spontaneous pituitary tumors is detected as an increase in uptake and BPND of (11)C-SA4503. Therefore, this tracer may have promise for the detection of pituitary adenomas, using PET.
authors.affiliation: Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Nisha K
authors.initials: NK
authors.lastname: Ramakrishnan
authors.forename: Anna A
authors.initials: AA
authors.lastname: Rybczynska
authors.forename: Anniek K D
authors.initials: AK
authors.lastname: Visser
authors.forename: Krisztina
authors.initials: K
authors.lastname: Marosi
authors.forename: Csaba J
authors.initials: CJ
authors.lastname: Nyakas
authors.forename: Chantal
authors.initials: C
authors.lastname: Kwizera
authors.forename: Jurgen W A
authors.initials: JW
authors.lastname: Sijbesma
authors.forename: Philip H
authors.initials: PH
authors.lastname: Elsinga
authors.forename: Kiichi
authors.initials: K
authors.lastname: Ishiwata
authors.forename: Jan
authors.initials: J
authors.lastname: Pruim
authors.forename: Rudi A J O
authors.initials: RA
authors.lastname: Dierckx
authors.forename: Aren
authors.initials: A
authors.lastname: van Waarde
mesh_terms: D000375:Aging; D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism; D007700:Kinetics; D008024:Ligands; D008297:Male; D010879:Piperazines / Q000097:blood / Q000378:metabolism* / Q000493:pharmacokinetics; D010911:Pituitary Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism; D049268:Positron-Emission Tomography / Q000379:methods*; D051381:Rats; D017208:Rats, Wistar; D017480:Receptors, sigma / Q000378:metabolism*; D014018:Tissue Distribution; D000097605:Sigma-1 Receptor
chemical_list: D008024:Ligands; D010879:Piperazines; D017480:Receptors, sigma; D000097605:Sigma-1 Receptor; C101789:SA 4503
keywords: 11C-SA4503; kinetic analysis; sigma receptor; small-animal PET; spontaneous pituitary tumor