Quantification of MAO B activity with [11C]L-deprenyl-D2

[11C]L-deprenyl-D2 (DEP-D) is used to measure the activity of monoamine oxidase B in the brain. Literature review on quantitative analysis of [11C]L-deprenyl-D2 PET brain studies is available in TPCMOD0033.

Analysis method in TPC

Preprocessing of the plasma input

For a detailed description on preprocessing of blood data, read the report TPCMOD0033 Appendix A. Below is a short instruction on how to do the processing with existing software.

Make sure that you have all the necessary data files:

  1. On-line blood sampler data file
  2. Dynamic PET image file from this study
    This file is used to correct for possible start time mismatch between PET scanner and blood sampling. If you are sure that both were started simultaneously, then you do not need the dynamic image file yet.
  3. Count-rate curve
  4. Plasma curve from manual sampling
  5. Blood curve from manual sampling
  6. Plasma parent fractions

Calculate the DEP-D plasma and total blood TACs, corrected for time delay, using either the GUI DEP-D_input (available only in TPC network with a Windows XP computer), or CLI script from Windows command line with command:

cscript P:\bin\windows\DEP-D_input.vbs

If you are sure that PET scan and blood sampling were started simultaneously, you do not need to enter the dynamic image file name; write None in the file name field instead.

Regional MAO B activity

Weights should be added to regional tissue data.

Fit irreversible two-tissue compartmental model to the regional data using PMOD or fitk3. Because of the relatively large variation in regional estimates for fitted vascular blood volume fraction (VB), we suggest that its value should be constrained in the fit, for example to 2.7%, that was the population average (n=15) in TPC. With fitk3 this can be done with option -Vb=2.7.

The most reliable model parameter for describing the activity of MAO B is λ×k3, where λ = K1/k2 (independent from perfusion), and k3 is proportional to the association constant kon (Fowler et al., 1995; Arakawa et al., 2017).

MAO B inhibition percentage

If two PET studies have been performed for each subject, one before (baseline) and one after (medication) dosage of a drug that occupies MAO B, the MAO B inhibition (EI) percentage can be computed as described here.

MAO B activity maps

Fowler and Logan have suggested a method to compute λ×k3 images.

To reduce the number of parameters to be estimated, a clustering algorithm which groups voxels with similar kinetics could be applied prior to the voxel analysis. In estimating the model parameters for each voxel, λ could then be fixed at the cluster value (Shumay et al., 2012).


See also:



References:

Arakawa R, Stenkrona P, Takano A, Nag S, Maior RS, Halldin C. Test-retest reproducibility of [11C]L-deprenyl-D2 binding to MAO-B in the human brain. EJNMMI Res. 2017; 7:54.

Analysis of [11C]L-deprenyl-D2 (DEP-D) brain PET studies. TPCMOD0033.

Analysis of [11C]L-deprenyl-D2 (DEP-D) brain PET studies: processing of blood data. TPCMOD0033 Appendix A (in TPC intranet).

Analysis of [11C]L-deprenyl-D2 (DEP-D) brain PET studies: compartment model analysis of regional data. TPCMOD0033 Appendix C (in TPC intranet).

Fowler JS, Wang GJ, Logan J, Xie S, Volkow ND, MacGregor RR, Schlyer DJ, Pappas N, Alexoff DL, Patlak C, Wolf AP. Selective reduction of radiotracer trapping by deuterium substitution: comparison of carbon-11-L-deprenyl and carbon-11-deprenyl-D2 for MAO B mapping. J Nucl Med. 1995; 36(7): 1255-1262.

Hirvonen J, Kailajärvi M, Haltia T, Koskimies S, Någren K, Virsu P, Oikonen V, Sipilä H, Ruokoniemi P, Virtanen K, Scheinin M, Rinne JO. Assessment of MAO-B occupancy in the brain with PET and [11C]-L-deprenyl-D2: a dose-finding study with a novel MAO-B inhibitor, EVT 301. Clin Pharmacol Ther. 2009; 85(5): 506-512.

Shumay E, Logan J, Volkow ND, Fowler JS. Evidence that the methylation state of the monoamine oxidase A (MAOA) gene predicts brain activity of MAOA enzyme in healthy men. Epigenetics 2012; 7(10): 1151-1160.

Sturm S, Forsberg A, Nave S, Stenkrona P, Seneca N, Varrone A, Comley RA, Fazio P, Jamois C, Nakao R, Ejduk Z, Al-Tawil N, Akenine U, Halldin C, Andreasen N, Ricci B. Positron emission tomography measurement of brain MAO-B inhibition in patients with Alzheimer’s disease and elderly controls after oral administration of sembragiline. Eur J Nucl Med Mol Imaging 2017; 44: 382-391.




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Created at: 2014-05-19
Updated at: 2017-06-26
Written by: Vesa Oikonen