Regional cerebral blood flow and distribution of [99mTc]ethyl cysteinate dimer in nonhuman primates.

Abstract

Increases in regional cerebral blood flow have been described in a variety of cerebral pathologic states, including stroke and seizure disorders. The usefulness of technetium-99m-labeled cysteinate dimer as a marker in the measurement of regional cerebral blood flow was tested in five cynomolgus monkeys. To expand the range of blood flow to beyond the normal limits, 40 mg/kg i.v. of the carbonic anhydrase inhibitor acetazolamide was administered. Regional cerebral blood flow in all five monkeys was measured using radiolabeled microspheres (before and after acetazolamide) and the marker (after acetazolamide) in 60-70 samples from 12 brain regions. Acetazolamide significantly increased the mean±SEM regional cerebral blood flow measured using microspheres from 0.56±0.21 to 1.71 ±0.9 ml/min/g (p<0.01 for each region). A significant positive correlation was found between regional cerebral blood flow values calculated using microspheres and the marker after normalizing the values to those in the cerebellum (r=0.773, /?< 0.0001). The mean±SEM regional cerebral blood flow determined using the marker in a single monkey (1.21 ±0.04 ml/min/g) did not differ significantly from that determined in the same monkey using microspheres (1.13±0.04 ml/min/g). These data support the potential use of this new brain perfusion imaging agent to assess regional cerebral blood flow over a clinically relevant range of blood flows. It is widely acknowledged that in several pathologic states, such as focal ictal seizures, brain tumors, and stroke during the subacute phase, locally increased metabolic demands increase rCBF to beyond the range observed under normal conditions. 45 Similar increases in rCBF are also pharmacologically induced clinically with agents such as the carbonic anhydrase inhibitor acetazolamide. These pharmacologic stress tests have been extensively used to evaluate cerebral vascular reserve in stroke patients. Received December 11, 1989; accepted March 21, 1990. cate perfusion alterations for which surgical interventions may be appropriate. A linear relation between rCBF and [ 99m Tc]ECD retention over a clinically relevant range of blood flows is needed before we can employ this new radiopharmaceutical agent in high-flow pathologic states and stress studies. We studied the relation between rCBF as measured with radiolabeled microspheres and ["""TcJECD retention during acetazolamide-induced hyperemia in nonhuman primates to evaluate the cerebral distribution of ["TcJECD at blood flow levels beyond the normal range. Materials and MethodsFive adult, male cynomolgus monkeys weighing 3.6-10.3 kg were food-deprived for approximately 20 hours, and water was removed on the morning of the study. The monkeys were anesthetized with 10 mg/kg i.m. ketamine hydrochloride and 1 mg/kg i.m. acepromazine maleate. Anesthesia was then maintained with a constant infusion of 1.5 mg/ml i.v. thiamylal sodium (Parke-Davis, Morris Plains, N.J.) delivered through a 22-gauge catheter inserted into a saphenous vein at a rate averaging <0.5 ml/mi...

Scaling of Brain Metabolism and Blood Flow in Relation to Capillary and Neural Scaling

“…The ethics statement does not apply to this study. CBF data were collected from different sources: for mouse [70], rat [71], rabbit [72], cynomolgus monkey [73], rhesus monkey [74], pig [75], and human [76]. Cerebral capillary characteristics were obtained from several sources: for mouse [14,51], rat [15,77,32], cat [40,78], dog [79], rhesus monkey [80], and human [33,34].…”

The acetylcholine releaser linopirdine increases parietal regional cerebral blood flow in Alzheimer's disease

“…It has been demonstrated to be a marker of regional cerebral perfusion (Orlandi et al 1990;Devous et al 1993). 99m Tc-ECD and its metabolites rapidly clear the blood, yielding high target-to-background imaging characteristics soon after injection (Léveillé et al 1989;Vallabhajosula et al 1989).…”

Zn Complex of Diaminedithiol Tetradentate Ligand as a Stable Precursor for 99mTc-Labeled Compounds

“…A presentative structure of DADT ligand is shown in Scheme 1, compound 6 (N 2 S 2 ). Indeed, 99m Tc-labeled N,N -ethylene bis (l-cysteine ethyl ester) has been used as a radiopharmaceutical for measuring cerebral blood flow [7]. However, further applications of DADT ligands are hindered due to the inherent easily oxidized property of the thiol groups during the storage.…”