Characterization of [11C]DASB and [18F]FE-PE2I using microPET imaging in SERT and DAT knockout rats

Cyprien G.J. Guerrin, Debbie R.M. Tesselaar, Emile E. Zweistra, Anna Cabiscol-Claveria, Bieneke Janssen, Janine Doorduin, Arnt F.A. Schellekens, Jan Booij, Judith R. Homberg
Nuclear Medicine and Biology. 2025-09-01; 148-149: 109055
DOI: 10.1016/j.nucmedbio.2025.109055

Guerrin CGJ(1), Tesselaar DRM(2), Zweistra EE(3), Cabiscol-Claveria A(3),
Janssen B(4), Doorduin J(5), Schellekens AFA(2), Booij J(6), Homberg JR(3).

Author information:
(1)Department of Medical Neuroscience, Donders Institute for Brain, Cognition,
and Behavior, Radboud University Medical Center, Nijmegen, the Netherlands.
Electronic address: .
(2)Department of Medical Neuroscience, Donders Institute for Brain, Cognition,
and Behavior, Radboud University Medical Center, Nijmegen, the Netherlands;
Department of Psychiatry, Radboud University Medical Center, Nijmegen, the
Netherlands; Nijmegen Institute for Scientist-Practitioners in Addiction
(NISPA), Nijmegen, the Netherlands.
(3)Department of Medical Neuroscience, Donders Institute for Brain, Cognition,
and Behavior, Radboud University Medical Center, Nijmegen, the Netherlands.
(4)Department of Medical Imaging, Radboud University Medical Center, Nijmegen,
the Netherlands; Department of Radiology and Nuclear Medicine, Amsterdam
University Medical Centers, location Vrije Universiteit Amsterdam, Amsterdam,
the Netherlands.
(5)Department of Nuclear Medicine and Molecular Imaging, University of
Groningen, University Medical Center Groningen, Groningen, the Netherlands.
(6)Department of Radiology and Nuclear Medicine, Amsterdam University Medical
Centers, Location Academic Medical Center, Amsterdam, the Netherlands;
Department of Medical Imaging, Radboud University Medical Center, Nijmegen, the
Netherlands.

RATIONALE: [11C]DASB is widely used for PET imaging of brain serotonin
transporters (SERT) and the tropane ligand [18F]FE-PE2I is used for PET imaging
of dopamine transporters (DAT). However, their in vivo selectivity has not been
confirmed using knockout (KO) models. This study aimed to provide direct in vivo
evidence for the selectivity of these tracers using SERT and DAT KO rats.
METHODS: High-resolution microPET imaging was performed in male SERT KO, DAT KO,
and wild-type (WT) rats. Animals were dynamically scanned either for 60 min with
[11C]DASB for SERT, or for 45 min with [18F]FE-PE2I for DAT. Binding potential
(BPND) was estimated using the simplified reference tissue model with the
cerebellum as reference. Whole-brain regions were analyzed for [11C]DASB, and
striatal regions for [18F]FE-PE2I using descriptive and effect size metrics.
RESULTS: Specific tracer binding was visually absent in KO animals across all
target regions. Quantitatively, [18F]FE-PE2I BPND in DAT KO rats was reduced by
94.2 % in the whole striatum, and [11C]DASB BPND in SERT KO rats was reduced by
a mean of 89.3 % across cortical, subcortical, and brainstem regions. These
reductions were associated with larger effect sizes (Cohen’s d ≥ 2.8).
CONCLUSION: This study provides in vivo characterization of [11C]DASB and
[18F]FE-PE2I selectivity and highlights the utility of genetic models for PET
tracer evaluation.

DOI: 10.1016/j.nucmedbio.2025.109055
PMID: 40779947 [Indexed for MEDLINE]

Conflict of interest statement: Declaration of competing interest The authors
declare the following financial interests/personal relationships which may be
considered as potential competing interests: JB is a consultant at GE Healthcare
(all related payments to the institute). The other authors declare that they
have no relevant financial or non-financial interests to disclose.