Feasibility of 62Cu-ATSM PET for evaluation of brain ischaemia and misery perfusion in patients with cerebrovascular disease

Abstract

[(62)Cu]Diacetyl-bis(N (4)-methylthiosemicarbazone) ((62)Cu-ATSM) was used to evaluate brain haemodynamic impairment in patients with cerebrovascular disease (CVD) as a simplified evaluation method. The tracer distribution was compared with haemodynamic parameters obtained by (15)O positron emission tomography (PET). Ten patients with major cerebral arterial occlusive disease (aged 66 ± 7 years) underwent PET with (62)Cu-ATSM and (15)O tracers ((15)O-water, (15)O(2) and C(15)O). Seven healthy volunteers also underwent (62)Cu-ATSM PET as normal controls. After the injection of (62)Cu-ATSM, 20-min dynamic PET data acquisition was started. Early- and delayed-phase images of (62)Cu-ATSM were obtained by averaging the initial 3-min and the last 10-min frame data, which were used for perfusion and retention images. Cerebral blood flow (CBF), blood volume, metabolic rate of oxygen (CMRO(2)) and oxygen extraction fraction (OEF) were measured by (15)O-gas and water studies and compared with early- and delayed-phase (62)Cu-ATSM images and delayed to early (D/E) ratio. Regional values were compared after all parametric images were coregistered to individual MRI. The asymmetry index (AI) was also calculated for OEF and Cu-ATSM D/E ratio, and diagnostic ability for detecting misery perfusion was compared. In the affected hemisphere of the patients, the mean values of haemodynamic parameters were CBF = 33.8 ± 5.9 ml/100 g per min, CMRO(2) = 2.6 ± 0.3 ml/100 g per min and OEF = 48 ± 7%. Standardized uptake values (SUVs) for (62)Cu-ATSM in early and delayed phases were 2.00 ± 0.13 and 1.04 ± 0.09 in the ipsilateral hemisphere and 2.13 ± 0.14 and 1.04 ± 0.08 in the contralateral hemisphere, respectively. The early-phase (62)Cu-ATSM images corresponded well to CBF images, and the D/E ratio images were similar to OEF images. Regional values obtained from D/E ratio images were significantly correlated with regional OEF. AIs of OEF and D/E ratio showed a significant correlation and diagnostic ability of misery perfusion was slightly better in AI of D/E ratio than that of OEF. Dynamic PET acquisition with (62)Cu-ATSM provided information on CBF distribution and local elevation of OEF in patients with chronic CVD. The findings of the present study showed the feasibility of the noninvasive molecular imaging method for diagnosing misery perfusion with a single venous tracer injection.