1-11C-methyl-4-piperidinyl-N-butyrate radiation dosimetry in humans by dynamic organ-specific evaluation.
Deficits of cholinergic neurotransmission contribute to various neurologic and psychiatric conditions. The neurotransmitter acetylcholine is hydrolyzed in the synaptic clefts by 2 enzymes, acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). 1-[(11)C]-Methyl-4-piperidinyl-N-butyrate ((11)C-MP4B) is a radioligand for the assessment study of BuChE activity in human brain with PET. In the present study the radiation-absorbed doses of the (11)C-MP4B were estimated in humans according to the guidelines of the International Commission on Radiological Protection. Two different data acquisition protocols-dynamic organ-specific evaluation (DOSE) and whole-body scanning-were compared. Both methods are widely used for evaluation of radiation burden of (11)C-labeled PET tracers.


METHODS
Fixed-bed PET on the upper neck, thorax, abdomen, or pelvic region was performed on 7 healthy subjects after injection of 707 +/- 34 MBq (mean +/- SD) of (11)C-MP4B. Brain input was derived from our previous studies on 18 healthy control subjects and 10 patients with Alzheimer's disease. Regions of interest were drawn on transverse images of all visible organs. Radiation dose estimates were calculated from organ residence times using the MIRDOSE3 software. Urine samples were collected after imaging to estimate tracer extraction. To compare the estimates for absorbed doses between the whole-body scan approach and the DOSE method, we simulated whole-body data acquisition methods used in (11)C dosimetry studies with our fixed-bed data.


RESULTS
The organs with the highest radiation-absorbed doses were the liver, urinary bladder, kidneys (renal cortex), upper large intestine, trabecular bone, salivary glands, and heart wall. Up to 60% of the injected dose was excreted via the urinary pathway, and the clearance was relatively rapid, as 30% of the radioactivity was excreted within 60 min after injection. With a 2-h voiding interval the effective dose was 4.2 microSv/MBq.


CONCLUSIONS
(11)C-MP4B causes less radiation burden than previously studied (11)C-labeled PET tracers. No intolerably high absorbed doses were observed in critical organs. With 740 MBq of injected radioactivity, the radiation burden is equivalent to 3.11 mSv. This would allow multiple PET examinations per year to be performed on the same subject. The DOSE method and the simulated whole-body imaging approach produced similar results.
Virta
Jere R
JR
Turku University Hospital, Turku PET Centre, Turku, Finland. jere.virta@utu.fi
Tolvanen
Tuula
T
Någren
Kjell
K
Brück
Anna
A
Roivainen
Anne
A
Rinne
Juha O
JO
D000328:Adult; D001822:Body Burden; D002087:Butyrates / Q000032:analysis / Q000493:pharmacokinetics*; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D008954:Models, Biological; D009928:Organ Specificity; D010880:Piperidines / Q000032:analysis / Q000493:pharmacokinetics*; D011829:Radiation Dosage; D019275:Radiopharmaceuticals / Q000032:analysis / Q000493:pharmacokinetics*; D012062:Relative Biological Effectiveness; D014018:Tissue Distribution; D014915:Whole-Body Counting
D002087:Butyrates; D010880:Piperidines; D019275:Radiopharmaceuticals; C496589:methyl-4-piperidinyl n-butyrate