Evaluation of copper(II)-pyruvaldehyde bis (N-4-methylthiosemicarbazone) for tissue blood flow measurement usina a trapped tracer model

Helen Young, Paul Carnochan, Jamal Zweit, John Babich, Simon R Cherry, Robert Ott

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

Copper(II)-pyruvaldehyde bis (N-4-methylthiosemicarbazone) (Cu-PTSM) labelled with 62,64Cu is a promising radiotracer for the study of blood flow using positron emission tomography (PET). We have investigated the application of a simple trapped tracer model to measurements of tissue 64Cu-PTSM uptake combined with continuous arterial sampling. A dual-tracer method was used to compare blood flow estimated by 64Cu-PTSM with values derived from measurements using cobalt-57 microspheres in the rat. Prolonged retention of 64Cu-PTSM following intravenous administration was initially confirmed in both normal tissues and tumours. After intraventricular 64Cu-PTSM infusion, cumulative arterial 64Cu activity increased progressively, and after extraction in n-octanol was found to plateau to levels corresponding with those reached following administration of 57CO microspheres. Rapid and species-dependent rates of 64Cu-PTSM decomposition to non-extractable 64Cu complexes were found in rat and human blood in vitro (70%±6% and 43%±5% respectively at 16 min), demonstrating the need for immediate processing of arterial samples. Close agreement was found between blood flow estimated by 64Cu-PTSM and 57CO microsphere methods in tissues of low to moderate flow: muscle (0.01, 0.08, 0.07 ml/min per gram; mean difference, mean 64Cu, mean 57Co), brain (0.09, 0.52, 0.43 ml/min per gram) and kidney (-0.16, 2.29, 2.45 ml/min per gram). Estimates of cardiac output also compared favourably between the two methods (5.7, 59.8, 54.1 ml/min). We conclude that a simple tissue trapping model may be suitable for the derivation of blood flow estimates using 62,64Cu-PTSM, PET imaging and continuous arterial blood sampling.

Original languageEnglish (US)
Pages (from-to)336-341
Number of pages6
JournalEuropean Journal Of Nuclear Medicine
Volume21
Issue number4
DOIs
StatePublished - Jan 1 1994
Externally publishedYes

Fingerprint

Pyruvaldehyde
Copper
Microspheres
Positron-Emission Tomography
1-Octanol
Cobalt
Intravenous Administration
Cardiac Output
Kidney
Muscles
Brain
Neoplasms

Keywords

  • Arterial sampling
  • Blood flow
  • Cu-PTSM
  • Microspheres

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

Cite this

Evaluation of copper(II)-pyruvaldehyde bis (N-4-methylthiosemicarbazone) for tissue blood flow measurement usina a trapped tracer model. / Young, Helen; Carnochan, Paul; Zweit, Jamal; Babich, John; Cherry, Simon R; Ott, Robert.

In: European Journal Of Nuclear Medicine, Vol. 21, No. 4, 01.01.1994, p. 336-341.

Research output: Contribution to journalArticle

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abstract = "Copper(II)-pyruvaldehyde bis (N-4-methylthiosemicarbazone) (Cu-PTSM) labelled with 62,64Cu is a promising radiotracer for the study of blood flow using positron emission tomography (PET). We have investigated the application of a simple trapped tracer model to measurements of tissue 64Cu-PTSM uptake combined with continuous arterial sampling. A dual-tracer method was used to compare blood flow estimated by 64Cu-PTSM with values derived from measurements using cobalt-57 microspheres in the rat. Prolonged retention of 64Cu-PTSM following intravenous administration was initially confirmed in both normal tissues and tumours. After intraventricular 64Cu-PTSM infusion, cumulative arterial 64Cu activity increased progressively, and after extraction in n-octanol was found to plateau to levels corresponding with those reached following administration of 57CO microspheres. Rapid and species-dependent rates of 64Cu-PTSM decomposition to non-extractable 64Cu complexes were found in rat and human blood in vitro (70{\%}±6{\%} and 43{\%}±5{\%} respectively at 16 min), demonstrating the need for immediate processing of arterial samples. Close agreement was found between blood flow estimated by 64Cu-PTSM and 57CO microsphere methods in tissues of low to moderate flow: muscle (0.01, 0.08, 0.07 ml/min per gram; mean difference, mean 64Cu, mean 57Co), brain (0.09, 0.52, 0.43 ml/min per gram) and kidney (-0.16, 2.29, 2.45 ml/min per gram). Estimates of cardiac output also compared favourably between the two methods (5.7, 59.8, 54.1 ml/min). We conclude that a simple tissue trapping model may be suitable for the derivation of blood flow estimates using 62,64Cu-PTSM, PET imaging and continuous arterial blood sampling.",
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