Kinetics of (R)-[11C] rolipram and (S)-[11C] rolipram In the Dog Heart: Investigation of Four Compartment Models
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Bibliographic record
Abstract
The PET tracers (R)-[ <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">11</sup> C]rolipram and (S)-[ <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">11</sup> C]rolipram have been proposed to measure phosphodiesterase-4 (PDE4) density as an indirect index of cAMP-mediated cell signaling, which is altered in many cardiac pathologies. The aim of this study was to determine which of the following models (if any) describe the kinetics of these tracers in normal dog hearts: a one-compartment model, a two-compartment model, and dual-input models comprising one or two compartments for rolipram and one compartment for labeled metabolites. Dynamic PET data were acquired from 6 healthy dogs with (R)-[ <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">11</sup> C]rolipram (10 studies) and (S)-[ <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">11</sup> C]rolipram (6 studies). Parameter estimates were obtained for 648 ROI's and median values determined. Distribution volumes were estimated from the parameter estimates. The one-compartment model did not fit the data acquired with either tracer adequately. Both the two-compartment model and the model comprising one compartment for the unchanged tracer and a parallel compartment to account for labeled metabolites provided good fits to the data obtained with (S)-[ <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">11</sup> C]rolipram (R-square: 0.99-1). The two-compartment model, with or without a parallel compartment to account for metabolites, described the kinetics of (R)-[ <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">11</sup> C]rolipram very well (R-square: 0.98-0.99). Estimates of the distribution volumes obtained with models that provided good fits to the data were very reproducible (CV: 10%-21%), suggesting that reliable measurement of PDE4 density in the heart may be possible.
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Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| 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 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
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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 it