Tracer clearance in radionuclide cisternography in patients with spontaneous intracranial hypotension.

We semiquantitatively analysed radionuclide cisternography in three patients with spontaneous cerebrospinal fluid (CSF) leakage diagnosed by typical symptoms and magnetic resonance imaging findings before and several months after treatment with epidural blood patch. Radioactivity in the whole CSF space was measured immediately after and at 1, 5, 7 and 24 h after intrathecal injection of (111)In-diethylenetriaminepentaacetic acid (DTPA). Initial findings included the vague appearance of leakage in the thoracic spine in two patients, early bladder filling at 1 h in one and a lack of tracer filling into the high cranial convexity in all three. The radioactivity count rapidly decreased within several hours after injection and reached 20% of the initial value at 24 h. In contrast, no rapid decrease was observed after treatment and more than 50% of tracer remained at 24 h after injection. Semiquantitative analysis of tracer clearance may provide additional information in the diagnosis of CSF leakage, especially with no obvious qualitative findings.

Tyramine neurotoxicity and first-pass brain technetium-99m-diethylenetriamine penta-acetic acid.

Tyramine induces coma in phenelzine-treated dogs with liver disease. The objective of the present investigation was to examine the influence of tyramine in these monoamine oxidase-inhibited dogs on the kinetics of Tc-99m-diethylenetriamine penta-acetic acid (Tc-99m-DTPA) during its first passage through the brain by nuclear imaging techniques. The study began with anesthetized mongrel dogs (n = 10) in a supine position over the camera detector. Data acquisition was started simultaneously after the rapid intracarotid injection of Tc-99m-DTPA (5 mCi) and 60 0.5-sec images of the brain were taken. Tyramine induced increased uptake with a concomitant impairment in the elimination of Tc-99m-DTPA from the brain of these phenelzine-treated animals with hepatic injury (n = 5) as compared to pretreated animals serving as a control group or phenelzine-treated animals without liver disease. This was accompanied by an appreciable reduction in hemispheric cerebral blood flow (50.5 +/- 19.3 vs. 110 +/- 16 ml/100 g/min), respectively. Increased cerebrovascular permeability of Tc-99m-DTPA and decreased cerebral blood flow occurred concomitantly with increased cerebrospinal fluid pressure and elevation in cerebrospinal fluid catecholamines of monoamine oxidase-inhibited animals with hepatic injury.

Active clearance of corticotropin-releasing factor from the cerebrospinal fluid.

Intracerebroventricular injection of corticotropin-releasing factor (CRF) in animals activates behavioral, motor, metabolic and sympathetic responses similar to those seen with stress. To explore the pharmacokinetics of this peptide in the primate ventricular CSF, we determined the clearance of ovine 125I-CRF from the CSF and compared it to that of 111In-DTPA, a substance cleared by bulk flow. 125I-CRF was cleared from the ventricular fluid sixfold more rapidly than bulk flow. This suggests that the CSF may be a pathway for physiological distribution of this releasing factor to active sites within the central nervous system, and that a mechanism exists for active removal of CRF from the ventricular CSF.

L-asparaginase pharmacokinetics and asparagine levels in cerebrospinal fluid of rhesus monkeys and humans.

L-Asparaginase has been widely used for the treatment of acute lymphoblastic leukemia. Therapeutic and toxic effects in the central nervous system have been noted with systemic treatment. In order to better define the relationship between L-asparaginase administration and cerebrospinal fluid (CSF) asparagine levels, L-asparaginase and asparagine were measured in the CSF of rhesus monkeys following intrathecal and i.v. administration. Following intrathecal injection, the enzyme activity of Escherichia coli L-asparaginase in the CSF demonstrated a more rapid terminal half-life than did that of 111In-labeled diethylenetriaminepentaacetic acid, a marker of CSF bulk flow [4 +/- 0.7 (S.D.) hr versus 5.8 +/- 0.2 hr]. Intrathecal injection of E. coli asparaginase resulted in complete depletion of CSF asparagine for at least 5 days. A similar period of CSF asparagine depletion was observed following i.v. administration of L-asparaginase. Similar results were found in seven patients undergoing systemic L-asparaginase therapy. The minimal plasma level of L-asparaginase necessary to deplete CSF asparagine in both species was 0.1 IU/ml. Two other enzymes, Erwinia L-asparaginase and succinylated Acinetobacter glutaminase-asparaginase, were cleared from the CSF at the same rate as bulk flow. These data indicate that systemic L-asparaginase therapy may be a feasible means of treating central nervous system involvement in patients with acute lymphoblastic leukemia and that there is no therapeutic advantage to using intrathecal L-asparaginase.

Ruthenium-97 DTPA: a new radiopharmaceutical for cisternography.

Ruthenium-97 DTPA (diethylenetriamine penta-acetic acid) was evaluated for its possible use as a cerebrospinal fluid imaging agent. Ru-97 has favorable physical properties that are highly suitable for imaging: decay by electron capture; gamma energy = 216 keV, 85%; T 1/2 = 2.9 days. Dogs were injected with 0.4 mCi Ru-97 DTPA or In-111 DTPA into the cisterna magna. The movement of the agents was monitored with a camera interfaced to a computer, or with a dual-probe system placed over the head and urinary bladder. In addition, blood and urine samples were collected at fixed intervals for 6 hr. High-quality images were obtained up to 48 hr after injection. The results show that the kinetics and excretion of Ru-97 DTPA are similar to those of In-111 DTPA. Radiation dose for identical activities is twice as high for In-111, in part because of greater abundance of the low-energy electron emission of In-111.