Peripheral metabolism of [18F]FDDNP and cerebral uptake of its labelled metabolites

Luurtsema, Gert; Schuit, Robert C.; Takkenkamp, Kevin; Lubberink, Mark; Hendrikse, N. Harry; Windhorst, Albert D.; Molthoff, Carla F.M.; Tolboom, Nelleke; van Berckel, Bart N.M.; Lammertsma, Adriaan A.

doi:10.1016/j.nucmedbio.2008.09.002

« Previous Next »Nuclear Medicine and Biology
Volume 35, Issue 8 , Pages 869-874, November 2008

Peripheral metabolism of [¹⁸F]FDDNP and cerebral uptake of its labelled metabolites☆

Gert Luurtsema
- Department of Nuclear Medicine and PET Research, VU University Medical Centre, PO Box 7057, 1007 MB Amsterdam, The Netherlands
- Corresponding author. Tel.: +31 0 20 4443999.
Robert C. Schuit
- Department of Nuclear Medicine and PET Research, VU University Medical Centre, PO Box 7057, 1007 MB Amsterdam, The Netherlands
Kevin Takkenkamp
- Department of Nuclear Medicine and PET Research, VU University Medical Centre, PO Box 7057, 1007 MB Amsterdam, The Netherlands
Mark Lubberink
- Department of Nuclear Medicine and PET Research, VU University Medical Centre, PO Box 7057, 1007 MB Amsterdam, The Netherlands
N. Harry Hendrikse
- Clinical Pharmacology and Pharmacy, VU University Medical Centre, PO Box 7057, 1007 MB Amsterdam, The Netherlands
Albert D. Windhorst
- Department of Nuclear Medicine and PET Research, VU University Medical Centre, PO Box 7057, 1007 MB Amsterdam, The Netherlands
Carla F.M. Molthoff
- Department of Nuclear Medicine and PET Research, VU University Medical Centre, PO Box 7057, 1007 MB Amsterdam, The Netherlands
Nelleke Tolboom
- Alzheimer Centre and Department of Neurology, VU University Medical Centre, PO Box 7057, 1007 MB Amsterdam, The Netherlands
Bart N.M. van Berckel
- Department of Nuclear Medicine and PET Research, VU University Medical Centre, PO Box 7057, 1007 MB Amsterdam, The Netherlands
Adriaan A. Lammertsma
- Department of Nuclear Medicine and PET Research, VU University Medical Centre, PO Box 7057, 1007 MB Amsterdam, The Netherlands

Received 20 June 2008; received in revised form 11 August 2008; accepted 5 September 2008.

Abstract

[¹⁸F]FDDNP is a positron emission tomography (PET) tracer for determining amyloid plaques and neurofibrillary tangles in the brain in vivo. In order to quantify binding of this tracer properly, a metabolite-corrected plasma input function is required. The purpose of the present study was to develop a sensitive method for measuring [¹⁸F]FDDNP and its radiolabelled metabolites in plasma. The second aim was to assess whether these radiolabelled metabolites enter the brain.

In humans, there was extensive metabolism of [¹⁸F]FDDNP. After 10 min, more than 80% of plasma radioactivity was identified as polar ¹⁸F-labelled fragments, probably formed from N-dealkylation of [¹⁸F]FDDNP. These labelled metabolites were reproduced in vitro using human hepatocytes. PET studies in rats showed that these polar metabolites can penetrate the blood–brain barrier and result in uniform brain uptake.

Keywords: [¹⁸F]FDDNP, Amyloid, Metabolism, BBB transport, PET