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Small Animal Imaging Resource Program @ Johns Hopkins

JHU/JHMI SAIRP

[11C]Carfentanil

[11C]Carfentanil (CFN) is a mu-opioid receptor agonist. CFN exhibits good reversibility, thus most simplified methods perform fairly well, however quantification with simplified methods is susceptible to bias in high binding regions.

References: Endres 2003

The methods

Compartmental modeling (blood input)
Rationale: Compartmental modeling with a blood input function is always considered the gold standard method of quantitation.
Advantages: The most thorough method, and generally, the most irrefutable technique.
Drawbacks: Arterial blood sampling is required; both the experiment and analysis are relatively difficult.
Techniques: First model the occipital cortex (OCC) to estimate non-specific binding. With non-specific binding held fixed, apply modeling to other regions to estimate CFN model parameters. Recommended to hold blood volume fixed.

Tissue-ratio method
Rationale: The ratio of CFN activity in a region with mu-opioid receptors to that in OCC is correlated with the level of specific binding in that region.
Advantages: Extremely simple method and blood sampling is avoided.
Drawbacks: Very high bias with a tendency to dramatically overestimate CFN binding.
Techniques: Generate TACs, then compute the ratio relative to OCC.

Reference tissue modeling
Rationale: There is very little mu-opioid binding in occipital cortex which serves as the reference region.
Advantages: Relatively simple method and blood sampling is avoided.
Drawbacks: Reference tissue methods tend to underestimate CFN binding potential in high density regions.
Techniques: Generate TACs, then apply the simplified reference tissue model (SRTM) with occipital cortex input.

Parametric mapping
Rationale: Either a one-tissue model, Logan with blood input, or several reference tissue approaches may be used to generate BP maps for carfentanil.
Advantages: Allows application of SPM analysis so that localization of binding changes is not constrained to a few predefined regions.
Drawbacks: As compared with region-of-interest analysis, may be less sensitive to measuring changes in uptake in high binding regions..
Techniques: Generate blood input function or OCC TAC, compute parametric images of BP, then apply SPM