Annals of Nuclear Medicine

, Volume 17, Issue 3, pp 249–253

Age-related changes of the [11C]CFT binding to the striatal dopamine transporters in the fischer 344 rats: a PET study

Short Communication


We investigated the age-related changes of the binding of [11C]CFT to striatal dopamine transporters (DATs)in vivo in Fischer 344 rats by positron emission tomography (PET). The tissue dissection method represented an age-related decrease in the uptake ratio of the striatum to the cerebellum and in the specific binding-to-nonspecific binding ratio of [11C]CFT. PET demonstrated an agedependent decrease in the striatal uptake of [11C]CFT, however, the kinetic analysis represented the age-related decrease in both the association rate constant (k3) and dissociation rate constant (k4), but not the binding potential (k3/k4) that was a parameter including both of density and affinity of the binding sites. The PET finding was not necessarily coincident with the result investigatedin vitro previously. Therefore, careful interpretation is necessary for PET studies using [11C]CFT and small animals such as rats.

Key words

aging dopamine transporter [11C]CFT positron emission tomography 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Fricker RA, Torres EM, Hume SP, Myers R, Opacka-Juffrey J, Ashworth S, et al. The effects of donor stage on the survival and function of embryonic striatal grafts in the adult rat brain. II. Correlation between positron emission tomography and reaching behavior.Neuroscience 1997; 79: 711–721.PubMedCrossRefGoogle Scholar
  2. 2.
    Haaparanta M, Bergman J, Laakso A, Hietala J, Solin O. [18F]CFT ([18F]WIN 35,428), a radioligand to study the dopamine transporter with PET: Biodistribution in rats.Synapse 1996; 23: 321–327.PubMedCrossRefGoogle Scholar
  3. 3.
    Hebert MA, Larson GA, Zahniser NR, Gerhardt GA. Age-related reductions in [3H]WIN 35,428 binding to the dopamine transporter in nigrostriatal and mesolimbic brain regions of the Fischer 344 rat.J Pharmacol Exp Ther 1999; 288: 1334–1339.PubMedGoogle Scholar
  4. 4.
    Hume SP, Lammertsma AA, Myers R, Rajeswaran S, Bloomfield PM, Ashworth S, et al. The potential of high-resolution positron emission tomography to monitor striatal dopaminergic function in rat models of disease.J Neurosci Methods 1996; 67: 103–122.PubMedGoogle Scholar
  5. 5.
    Ishiwata K, Koyanagi Y, Saitoh T, Taguchi K, Toda J, Sano T, et al. Effects of single and repeated administration of 1,2,3,4-tetrahydroisoquinoline analogs on the binding of [11C]raclopride to dopamine D2 receptors in the mouse brain.J Neural Transm 2001; 108: 1111–1125.PubMedCrossRefGoogle Scholar
  6. 6.
    Ishiwata K, Hayakawa N, Ogi N, Oda K, Toyama H, Endo K, et al. Comparison of three PET dopamine D2-like receptor ligands, [11C]raclopride, [11C]nemonapride and [11C]N-methylspiperone in rats.Ann Nucl Med 1999; 13: 161–167.PubMedCrossRefGoogle Scholar
  7. 7.
    Ishiwata K, Ogi N, Hayakawa N, Umegaki H, Nagaoka T, Oda K, et al. Positron emission tomography andex vivo andin vitro autoradiography studies on dopamine D2-like receptor degeneration in the quinolinic acid-lesioned rat striatum: comparison of [11C]raclopride, [11C]nemonapride and [11C]N-methylspiperone.Nucl Med Biol 2002; 29: 307–316.PubMedCrossRefGoogle Scholar
  8. 8.
    Kaufman NJ, Madras BK. [3H]CFT ([3H]WIN 35,428) accumulation in dopamine regions of monkey brain: Comparison of a mature and an aged monkey.Brain Res 1993; 611: 322–325.PubMedCrossRefGoogle Scholar
  9. 9.
    Kawamura K, Ishiwata K, Futatsubashi M, Ishii S, Ouchi Y, Homma Y, et al. Efficient HPLC separation of [11C]β-CFT or [11C]β-CIT fromN-desmethyl precursor on a semipreparative reversed phase ODS column.Appl Radiat Isot 2000; 52: 225–228.PubMedCrossRefGoogle Scholar
  10. 10.
    Laakso A, Bergmann J, Haaparanta M, Vilkman H, Solin O, Hietala J. [18F]CFT ([18F]WIN 35,428), a radioligand to study the dopamine transporter with PET: Characterization in human subjects.Synapse 1998; 28: 244–250.PubMedCrossRefGoogle Scholar
  11. 11.
    Neumeyer JL, Tamagnan G, Wang S, Gao Y, Milius RA, Kula NS, et al.N-substituted analogs of 2β-carbomethoxy-3β-(4′-iodophenyl)tropane (β-CIT) with selective affinity to dopamine or serotonin transporters in rat forebrain.J Med Chem 1996; 39: 543–548.PubMedCrossRefGoogle Scholar
  12. 12.
    Ogawa O, Umegaki H, Ishiwata K, Asai Y, Ikari H, Oda K, et al.In vivo imaging of adenovirus-mediated over-expression of dopamine D2 receptors in rat striatum by positron emission tomography.Neuroreport 2000; 11: 743–748.PubMedCrossRefGoogle Scholar
  13. 13.
    Suzuki M, Hatano K, Sakiyama Y, Kawasumi Y, Kato T, Ito K. Age-related changes of dopamine D1-like and D2-like receptor binding in the F344/N rat striatum revealed by positron emission tomography andin vitro receptor autoradiography.Synapse 2001; 41: 285–293.PubMedCrossRefGoogle Scholar
  14. 14.
    Tsukada H, Kreuter J, Maggos CE, Unterwald EM, Kakiuchi T, Nishiyama S, et al. Effects of binge pattern cocaine administration on dopamine D1 and D2 receptors in the rat brain: anin vivo study using positron emission tomography.J Neurosci 1996; 16: 7670–7677.PubMedGoogle Scholar
  15. 15.
    Tsukada H, Nishiyama S, Kakiuchi T, Ohba H, Sato K, Harada N, et al. Isoflurare anesthesia enhances the inhibitory effects of cocaine and GBR12909 on dopamine transporter: PET studies in combination with microdialysis in the monkey brain.Brain Res 1999; 849: 85–96.PubMedCrossRefGoogle Scholar
  16. 16.
    Umegaki H, Ishiwata K, Ogawa O, Ingram DK, Roth GS, Yoshimura J, et al.In vivo assessment of adenoviral vector-mediated gene expression of dopamine D2 receptors in the rat striatum by positron emission tomography.Synapse 2002; 43: 195–200.PubMedCrossRefGoogle Scholar

Copyright information

© Springer 2003

Authors and Affiliations

  • Kazunori Kawamura
    • 2
    • 1
  • Keiichi Oda
    • 2
  • Kiichi Ishiwata
    • 2
  1. 1.SHI Accelerator Service Ltd.Japan
  2. 2.Positron Medical CenterTokyo Metropolitan Institute of GerontologyTokyoJapan

Personalised recommendations