PT  - JOURNAL ARTICLE
AU  - Sandra Sanabria-Bohorquez
AU  - Koen Van Laere
AU  - Terence Hamill
AU  - G. Bormans
AU  - Inge De Lepeleire
AU  - Tom Reynders
AU  - Robert Iannone
AU  - Anne Van Hecken
AU  - David Mozley
AU  - Donald Burns
TI  - Evaluation of the histamine H3 receptor tracer [11C]MK-8278 in human
DP  - 2009 May 01
TA  - Journal of Nuclear Medicine
PG  - 1212--1212
VI  - 50
IP  - supplement 2
4099  - http://jnm.snmjournals.org/content/50/supplement_2/1212.short
4100  - http://jnm.snmjournals.org/content/50/supplement_2/1212.full
SO  - J Nucl Med2009 May 01; 50
AB  - 1212 Objectives [11C]MK-8278 is a high affinity, selective inverse agonist PET tracer for the presynaptic histamine H3 receptor which has been implicated in various neurological diseases. Preliminary human dosimetry and brain tracer kinetics is presented. Methods MK-8278 dosimetry was evaluated in 3 subjects who underwent serial whole-body PET-CT for 2h. Source organs were delineated using morphological and functional data. Residence times were derived from time-activity profiles. Individual organ doses and effective doses (ED) were determined using the OLINDA/EXM. MK-8278 brain kinetics and test-retest reproducibility was evaluated in 3 additional subjects, two 100 min scans on the same day. [11C]MK-8278 arterial plasma input function was estimated using total activity counts and the relative plasma fraction. Logan graphical analysis was used to estimate VT. Results Dosimetry estimates resulted in an ED of 5.45±1.08 μSv/MBq. Highest organ doses were observed for lung (2.2 μGy/MBq), liver (0.65μGy/MBq) and small intestine (0.53 μGy/MBq). Rapid brain penetration was observed. The highest MK-8278 uptake was observed in the striatum (VT=17), followed by cortex (VT=8) and cerebellum (VT=7). Low binding was observed in the pons (VT=5) with tracer uptake similar to white matter at later time points. Stable VT estimates could be obtained using only 60 min data. Test-retest variability was below 10%. Conclusions MK-8278 has an acceptable ED which allows multiple brain scans of good image quality. MK-8278 kinetic data acquired for 60 min can be used to reliably quantify H3 receptor availability in humans.