Characterization of the SPECT 5-HT2A receptor ligand 123I-R91150 in healthy volunteers: Part 1--pseudoequilibrium interval and quantification methods.
Bibliographic record
Abstract
UNLABELLED: With the aim of characterizing radioiodinated 4-amino-N-1-[3-(4-fluorophenoxy)propyl]-4-methyl-4-piperidinyl]5-iodo-2-methoxybenzamide ((123)I-R91150) as a SPECT ligand for subtype 2A of the 5-hydroxytryptamine receptor (5-HT(2A)), tracer kinetic compartmental analyses were compared with the tissue ratio method (TR). The pseudoequilibrium interval after a single bolus injection was identified, and a reference database of specific uptake ratio (SUR) values was obtained. Within-scan and between-subject variability was also assessed. METHODS: Nineteen healthy men (mean age +/- SD, 24.4 +/- 3.3 y) were included and separated into 2 groups. Dynamic scans with venous blood sampling from 0 to 470 min after a single bolus injection of (123)I-R91150 was completed for 7 of the 9 subjects included in group A, and in one of them compartmental modeling was performed with an arterial blood input function using 1-tissue-compartment (1TC) and 2-tissue-compartment (2TC) models. Binding potential (BP) using the simplified reference tissue model (SRTM) (BP(SRTM)) and SUR values using TR over time were also calculated. The 10 remaining subjects (group B) underwent a single scan at pseudoequilibrium with the aim of improving the precision of mean normal SUR estimates. Regions of interest in cortical regions and basal ganglia for specific uptake, and in cerebellum for nonspecific uptake, were manually drawn on each subject's MR images and translated to the corresponding SPECT slices after coregistration. RESULTS: The 1TC model correlated well with the 2TC model (BP(2TC) = 1.04.BP(1TC) - 0.01, R(2) = 0.98), and both methods correlated with BP(SRTM) and SUR with little bias (BP(1TC) = 1.10 BP(SRTM) + 0.03, R(2) = 0.98; BP(2TC) = 1.15 BP(SRTM) + 0.01, R(2) = 0.98; BP(SRTM) = 0.99 SUR(mean) + 0.01, R(2) = 0.98). SUR values stabilized from 180 min after injection in most cortical regions, ranging from 0.51 +/- 0.10 in the orbitofrontal region to 0.27 +/- 0.09 in the parietal region. Within-scan and between-subject variability among regions ranged from 10% to 14.8%, and from 18.3% to 35.4%, respectively. CONCLUSION: (123)I-R91150 distribution agrees with autoradiography results, showing highly specific binding in cortical regions. The correlations found among 1TC, 2TC, SRTM, and TR outcome measurements support the use of TR for quantification of 5-HT(2A) receptor binding with (123)I-R91150 SPECT and a simple protocol avoiding arterial blood sampling and serial scanning over time.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".