TY - JOUR T1 - Molecular Imaging of Neurovascular Cell Death in Experimental Cerebral Stroke by PET JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 1520 LP - 1528 DO - 10.2967/jnumed.107.043919 VL - 49 IS - 9 AU - Ayelet Reshef AU - Anat Shirvan AU - Rikki N. Waterhouse AU - Hagit Grimberg AU - Galit Levin AU - Avi Cohen AU - Luckner G. Ulysse AU - Gad Friedman AU - Gunnar Antoni AU - Ilan Ziv Y1 - 2008/09/01 UR - http://jnm.snmjournals.org/content/49/9/1520.abstract N2 - Clinical molecular imaging of apoptosis is a highly desirable yet unmet challenge. Here we provide the first report on 18F-labeled 5-fluoropentyl-2-methyl-malonic acid (18F-ML-10), a small-molecule, 18F-labeled PET tracer for the imaging of apoptosis in vivo; this report includes descriptions of the synthesis, radiolabeling, and biodistribution of this novel apoptosis marker. We also describe the use of 18F-ML-10 for small-animal PET of neurovascular cell death in experimental cerebral stroke in mice. Methods: 18F-ML-10 was synthesized by nucleophilic substitution from the respective mesylate precursor, and its biodistribution was assessed in healthy rats. Permanent occlusion of the middle cerebral artery (MCA) was induced in mice, and small-animal PET was performed 24 h later. Results: Efficient radiolabeling of ML-10 with 18F was achieved. Biodistribution studies with 18F-ML-10 revealed rapid clearance from blood (half-life of 23 min), a lack of binding to healthy tissues, and rapid elimination through the kidneys. No significant tracer metabolism in vivo was observed. Clear images of distinct regions of increased uptake, selectively in the ischemic MCA territory, were obtained in the in vivo small-animal PET studies. Uptake measurements ex vivo revealed 2-fold-higher uptake in the affected hemisphere and 6- to 10-fold-higher uptake in the region of interest of the infarct. The cerebral uptake of 18F-ML-10 was well correlated with histologic evidence of cell death. The tracer was retained in the stroke area but was cleared from blood and from intact brain areas. Conclusion: 18F-ML-10 is useful for noninvasive PET of neurovascular histopathology in ischemic cerebral stroke in vivo. Such an assessment may assist in characterization of the extent of stroke-related cerebral damage and in the monitoring of disease course and effect of treatment. ER -