RT Journal Article
SR Electronic
T1 Evaluation of the histamine H3 receptor tracer [11C]MK-8278 in human
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 1212
OP 1212
VO 50
IS supplement 2
A1 Sandra Sanabria-Bohorquez
A1 Koen Van Laere
A1 Terence Hamill
A1 G. Bormans
A1 Inge De Lepeleire
A1 Tom Reynders
A1 Robert Iannone
A1 Anne Van Hecken
A1 David Mozley
A1 Donald Burns
YR 2009
UL http://jnm.snmjournals.org/content/50/supplement_2/1212.abstract
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.