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to the striatum

OK. What if we don’t care about the kinetics of a particular tracee molecule (e.g., glucose). Rather, we care about counting up the number of one type of helper molecules. Recall the tragic heroin addict, David, in 1977, cited in a previous reading….

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to the striatum

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  1. OK. What if we don’t care about the kinetics of a particular tracee molecule (e.g., glucose).Rather, we care about counting up the number of one type of helper molecules.Recall the tragic heroin addict, David, in 1977, cited in a previous reading…

  2. David had attempted to make a heroin-like substance, MPPP, in his bathtub and instead had made MPTP. MPTP is a poison that destroys neurons via entry through the Dopamine transporter molecules on those neurons. How might we image the loss of David’s nigro-striatal neurons? from the substantia nigra to the striatum

  3. Recall that DAT molecules soak up excess Dopamine after it is fired into the synapse by the pre-synaptic neuron. In particular the neurons that run from the substantia nigra to the striatum. Loss of nigral-striatal neurons is also the primary pathology in Parkinson’s disease. If we could detect early loss of nigro-striatal projections by detecting loss of DAT on the ends of these neurons, we might have an early diagnosis method for Parkinson’s. from the substantia nigra to the striatum Hint: make this thing radioactive

  4. From 1-compartment to 2- or 3-compartment models. Common application: receptor-ligand modeling What does this model ‘say’? Why is the PET pixel drawn as shown? K1 & k2 are still the blood flow parameters.

  5. General PET kinetic model PET = weighted sum of activity from ligand in various compartments. But, there are multiple comparments. (Ci = [ F B NS ]). Hence multiple….ODEs!!!

  6. But what’s really Special about PET? Molecular Specificity! Introduction to PET Modeling

  7. receptor blood vessel radio-ligand nerve terminal What’s in a (Brain) Pixel?

  8. Plasma Free Bound Non-specifc What’s in an Abstract (Brain) Pixel? Possible ligand ‘states’: Intravascular Free Bound specifically Non-displaceable

  9. P F B N What do the Boxes Signify? Mass Balances:

  10. P F B N What do the Boxes Signify? Mass Balances: (more precise) …whereas with FDG we had to be concerned with the effects of glucose, (recall fast vs fed mice) now we need to keep track of cold (not labeled tracer).

  11. P F B N Mass Balances: Why no Mass Balance on P? = P(t) is a measured quantity P

  12. Input Function P time What’s needed to Solve the Model? Input Function, P, Drives the Model.

  13. How to Model Receptor-Ligand Interactions for Non-equilibrium Kinetics? rate constant * [available receptors] * [radioligand] rate constant * [available receptors] * [radioligand] rate constant * [available receptors] * [radioligand] Bimolecular and Saturable!

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