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Evaluation of a Potential Generator-Produced PET Tracer for Cerebral Perfusion Imaging: Single-Pass Cerebral Extraction Measurements and Imaging with Radiolabeled Cu-PTSM

Department of Radiology, Washington University School of Medicine, St. Louis, Missouri
MURR University of Missouri, Columbia, Missouri
School of Pharmacy, Purdue University, West Lafayette, Indiana

Correspondence: For reprints contact: Carla J. Mathias, Washington University, The Edward Mallinckrodt Institution of Radiology, 510 S. Kingshighway, St. Louis, MO 63110.

ABSTRACT

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 mm) (1). To evaluate the potential of Cu-PTSM for CBF PET studies, baboon single-pass cerebral extraction measurements and PET imaging were earned out with the use of ⁶⁷Cu(t_1/2 = 2.6 days) and ⁶⁴Cu (t_1/2 = 12.7 hr), respectively (1). 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 H₂¹⁵O 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 H₂¹⁵O 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 H₂¹⁵O. This data suggests that [⁶²Cu]-Cu-PTSM may be a useful generator-produced radiopharmaceutical for blood flow studies with PET.

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