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Accurate Reference Region Calculation in Mouse Brain [18F]fallypride Studies.

Alan Miranda1,2, Filipe Elvas3, Steven Staelens3,4

  • 1Molecular Imaging Center Antwerp, University of Antwerp, Universiteitsplein 1, 2610, Antwerp, Belgium. alan.mirandamenchaca@uantwerpen.be.

Molecular Imaging and Biology
|April 20, 2026
PubMed
Summary
This summary is machine-generated.

Non-negative matrix factorization (NMF) accurately quantifies dopamine D2/3 receptors by extracting uncontaminated reference region time activity curves. This method improves detection of drug challenge effects compared to traditional cerebellum reference regions.

Keywords:
Dopamine receptorsKinetic modellingNonnegative matrix factorizationPositron emission tomography

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Area of Science:

  • Neuroscience
  • Radiochemistry
  • Medical Imaging

Background:

  • Quantification of dopamine D2/3 receptors using [18F]fallypride tracer typically relies on cerebellum as a reference region for kinetic modeling.
  • In mouse studies, [18F]fallypride defluorination leads to skull uptake, contaminating cerebellum activity and introducing errors in reference region kinetic modeling.
  • Extra-striatal binding and skull spill-over can compromise the accuracy of traditional reference region methods.

Purpose of the Study:

  • To develop and validate a novel method using non-negative matrix factorization (NMF) for accurate extraction of reference region time activity curves (TACs).
  • To assess the performance of NMF in a drug challenge study and compare it with a standard eroded cerebellum reference region method.
  • To evaluate the impact of NMF on the quantification of nondisplaceable binding potential (BPND) and the detection of drug-induced changes.

Main Methods:

  • Non-negative matrix factorization (NMF) was employed to extract reference region TACs, minimizing contamination from surrounding tissues.
  • The NMF method was compared against a template-based eroded cerebellum (erodedCB) reference region method.
  • Both methods were applied in a drug challenge study using RX821002 and compared with results from [11C]raclopride.

Main Results:

  • NMF-derived reference region TACs exhibited higher peak and lower tail activity compared to erodedCB.
  • Striatal BPND values calculated using NMF were approximately 20% higher than those from erodedCB.
  • The NMF method revealed a greater increase in BPND between baseline and challenge (11.5%) compared to erodedCB (7.0%), with NMF identifying significant differences not detected by erodedCB.

Conclusions:

  • Non-negative matrix factorization (NMF) provides a robust method for extracting uncontaminated reference region TACs, unaffected by skull or extra-striatal uptake.
  • NMF enhances the voxel-wise detection of differences in drug challenge studies, offering improved sensitivity for detecting pharmacological effects.
  • The NMF approach offers a significant advancement in the accurate quantification of dopamine D2/3 receptors and the assessment of their modulation in vivo.