Evaluation of a potential generator-produced PET tracer for cerebral perfusion imaging: Single-pass cerebral extraction measurements and imaging with radiolabeled Cu-PTSM

Copper(II) pyruvaldehyde bis(N⁴-methylthiosemicarbazone) (Cu-PTSM), copper(II) pyruvaldehyde bis(N⁴-dimethylthiosemicarbazone) (Cu-PTSM₂), and copper(II) ethylglyoxal bis(N⁴-methylthiosemicarbazone) (Cu-ETSM), have been proposed as PET tracers for cerebral blood flow (CBF) when labeled with generator-produced ⁶²Cu (t( 1/2 ) = 9.7 min). To evaluate the potential of Cu-PTSM for CBF PET studies, baboon single-pass cerebral extraction measurements and PET imaging were carried out with the use of ⁶⁷Cu (t( 1/2 ) = 2.6 dyas) and ⁶⁴Cu (T( 1/2 ) = 12.7 hr), respectively. All three chelates were extracted into the brain with high efficiency. There was some clearance of all chelates in the 10-50-sec time frame and Cu-PTSM₂ continued to clear. Cu-PTSM and Cu-ETSM have high residual brain activity. PET imaging of baboon brain was carried out with the use of [⁶⁴Cu]-Cu-PTSM. For comparison with the ⁶⁴Cu brain image, a CBF )¹⁵O-labeled water) image (40 sec) was first obtained. Qualitatively, the H₂ ¹⁵O and [⁶⁴Cu]-Cu-PTSM images were very similar; for example, a comparison of gray to white matter uptake resulted in ratios of 2.42 for H₂ ¹⁵O and 2.67 for Cu-PTSM. No redistribution of ⁶⁴Cu was observed in 2 hr of imaging, as was predicted from the single-pass study results. Quantitative determination of blood flow using Cu-PTSM showed good agreement with blood flow determined with H₂ ¹⁵O. This data suggests that [⁶²Cu]-Cu-PTSM may be a useful generator-produced radiopharmaceutical for blood flow studies with PET.