Reference tissue models and blood-brain barrier disruption: lessons from (R)-[11C]PK11195 in traumatic brain injury

J Nucl Med. 2009 Dec;50(12):1975-9. doi: 10.2967/jnumed.109.067512. Epub 2009 Nov 12.

Abstract

(R)-[(11)C]PK11195 is a tracer for activated microglia. The purpose of this study was to assess the validity of the simplified reference tissue model for analyzing (R)-[(11)C]PK11195 studies in traumatic brain injury (TBI), where blood-brain barrier disruptions are likely.

Methods: Dynamic (R)-[(11)C]PK11195 scans were acquired at 3 time points after TBI. Plasma input-derived binding potential (BP(ND)(PI)), volume of distribution (V(T)) and K(1)/k(2), and simplified reference tissue model-derived binding potential (BP(ND)(SRTM)) were obtained. Simulations were performed to assess the effect of varying K(1)/k(2).

Results: Early after TBI, an increase in V(T), but not in BP(ND)(PI), was found. Early K(1)/k(2) correlated with V(T) and BP(ND)(SRTM) but not with BP(ND)(PI). One and 6 mo after TBI, BP(ND)(SRTM) correlated with BP(ND)(PI).

Conclusion: Early after TBI, (R)-[(11)C]PK11195 studies should be analyzed using plasma input models.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Amides / metabolism*
  • Blood-Brain Barrier / diagnostic imaging
  • Blood-Brain Barrier / metabolism*
  • Blood-Brain Barrier / pathology*
  • Brain Injuries / diagnostic imaging
  • Brain Injuries / metabolism*
  • Brain Injuries / pathology*
  • Case-Control Studies
  • Female
  • Humans
  • Isoquinolines / metabolism*
  • Male
  • Middle Aged
  • Models, Biological*
  • Positron-Emission Tomography / standards*
  • Reference Values
  • Reproducibility of Results
  • Young Adult

Substances

  • (R)-(11C)1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinolinecarboxamide
  • Amides
  • Isoquinolines