PET Imaging of Adenosine A1 Receptors with 11C-MPDX as an Indicator of Severe Cerebral Ischemic Insult

PET Imaging of Adenosine A₁ Receptors with ¹¹C-MPDX as an Indicator of Severe Cerebral Ischemic Insult

Tadashi Nariai, MD, PhD¹, Yuhei Shimada, PhD², Kiichi Ishiwata, PhD³, Tsukasa Nagaoka, MD¹, Junichi Shimada, PhD⁴, Toshihiko Kuroiwa, MD, PhD⁵, Ken-Ichiro Ono, PhD², Kikuo Ohno, MD, PhD¹, Kimiyoshi Hirakawa, MD, PhD¹ and Michio Senda, MD, PhD³

¹ Department of Neurosurgery, Tokyo Medical and Dental University, Tokyo, Japan
² Department of Veterinary Clinical Pathobiology, University of Tokyo, Tokyo, Japan
³ Positron Medical Center, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan
⁴ Pharmaceutical Research Laboratories, Kyowa Hakko Kogyo Co., Ltd., Tokyo, Japan
⁵ Department of Neuropathology, Tokyo Medical and Dental University, Tokyo, Japan

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FIGURE 1. Bar graphs indicate PET parameters, including right-to-left ratio of CBF during occlusion of MCA (A), CBF after reperfusion (B), ¹⁸F-FDG uptake as indicator of CMRGlc (C), MPDX binding to A1-Rs (D), and FMZ binding to BDZ-Rs (E), in ischemic cortex for each animal group. ANOVA and multiple comparisons between 6 pairs were performed by Bonferroni correction. CBF was reduced in all treated groups, but rate of reduction was not significantly different among them. No statistical difference among the 4 groups was found in right-to-left ratio of CBF or CMRGlc after reperfusion. MPDX binding was significantly lower in group D than in groups N, Str, and Cor. MPDX binding in group Cor was significantly lower than that in group N. FMZ binding was significantly lower in group D than in groups N and Str. Reductions of A1-Rs and BDZ-Rs were both good indicators of permanent ischemic insult, whereas reduction rate of MPDX binding to A1-Rs in group D was larger than that of FMZ binding to BDZ-Rs. *P < 0.05. **P < 0.01.

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FIGURE 2. PET images display CBF before (Pre), during (Occ), and after (Rep) occlusion of MCA; uptake of ¹⁸F-FDG; MPDX binding to A1-R; and FMZ binding to BZD-R for each animal group. Each PET image was coregistered with animal’s own MR image, and corresponding coronal plane is shown for each parameter. (MRI was not performed for group D animals.) Group Str did not show any conspicuous abnormality in CMRGlc or radioligand binding to A1-R or BZD-R. Reduction in radioligand binding to A1-R and BZD-R was noted in both animals from group Cor. Of these 2 receptor ligands, area with decreased binding of MPDX to A1-R represented subsequent cortical infarction with better contrast (white arrows). However, CBF and CMRGlc both decreased in first Cor animal, whereas they both increased in second Cor animal. This may have explained poor performance of CBF and CMRGlc in predicting degree of ischemic insult soon after reperfusion. MPDX binding was reduced most prominently in group D, reaching almost zero (yellow arrow). FMZ binding and CMRGlc also decreased in group D, but not as prominently as MPDX binding. Color scale of images is displayed on right. Images CBF, A1-R, BZD-R, and ¹⁸F-FDG are depicted in units of mL/min/100 mL, Bq/mL, Bq/mL, and standardized uptake value, respectively. Color scale for each animal was set so that control sides would indicate similar color level.