title: Evaluation of a potential generator-produced PET tracer for cerebral perfusion imaging: single-pass cerebral extraction measurements and imaging with radiolabeled Cu-PTSM.
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 (t1/2 = 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 (t1/2 = 2.6 days) and 64Cu (t1/2 = 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(15)O 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(15)O 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(15)O. This data suggests that [62Cu]-Cu-PTSM may be a useful generator-produced radiopharmaceutical for blood flow studies with PET.
authors.affiliation: Department of Radiology, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: C J
authors.initials: CJ
authors.lastname: Mathias
authors.forename: M J
authors.initials: MJ
authors.lastname: Welch
authors.forename: M E
authors.initials: ME
authors.lastname: Raichle
authors.forename: M A
authors.initials: MA
authors.lastname: Mintun
authors.forename: L L
authors.initials: LL
authors.lastname: Lich
authors.forename: A H
authors.initials: AH
authors.lastname: McGuire
authors.forename: K R
authors.initials: KR
authors.lastname: Zinn
authors.forename: E K
authors.initials: EK
authors.lastname: John
authors.forename: M A
authors.initials: MA
authors.lastname: Green
mesh_terms: D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging*; D002560:Cerebrovascular Circulation / Q000502:physiology*; D003301:Copper Radioisotopes; D008297:Male; D009942:Organometallic Compounds; D010215:Papio; D013882:Thiosemicarbazones; D014055:Tomography, Emission-Computed
chemical_list: D003301:Copper Radioisotopes; D009942:Organometallic Compounds; D013882:Thiosemicarbazones; C063294:copper (II) ethylglyoxal bis(N(4)-methylthiosemicarbazone); C052629:copper pyruvaldehyde bis(N(4)-methylthiosemicarbazone) complex; C063293:copper (II) pyruvaldehyde bis(N(4)-dimethylthiosemicarbazone)