Project Identifier: BNL-94-144B
Project Title:
Evaluation of 18-FDG in the Diagnosis of Glucose Metabolism in the Human Body (Cocaine Abusers)
Principle Investigator:
Dr. Joanna S. Fowler
Project started in: 1994
Project Funding Information:
Project received funding in Fiscal Year 1995.
Project used human subjects in Fiscal Year 1995.
Funding Sources:
DA 06891
Project does not involve use of multiple protocols/subprojects.
IRB Review:
Type of Review: Full Board
Most Recent Approval: January 01, 1995
Number of Human Subjects in the Last Reporting Period for this Project: 11
(Reporting periods vary.)
Type of Human Subjects Involvement:
Internal administration of radioactive substances to human subjects.
The purpose of these studies is to investigate the involvement of the dopamine (DA) system in cocaine addiction. More specifically, these studies use positron emission tomography (PET) to evaluate if decreased frontal metabolism in cocaine abusers is related to decreased function of presynaptic DA neurons (PDN). PDN function is evaluated in cocaine abusers and normal controls by monitoring DA release in response to methylphenidate (MP), a drug that increases synaptic DA by inhibiting DA transporter sites. Changes in DA concentration after MP are evaluated by measuring its effects on 11-C-Raclopride binding and on glucose metabolism. Because DA competes with 11-C-Raclopride for the DA D-2 receptors, this strategy enables us to assess relative changes in DA induced by MP. We also assess the effects of MP on frontal brain glucose metabolism (FDG) to evaluate in the same individual the relationship between changes in DA and changes in regional brain metabolism.
Radioactive substances include F-18-Fluorodeoxyglucose (F-18-FDG) and C-11-Raclopride. Chemical substances include methylphenidate. The subjects have a short-lived positron emitter tracer administered and are subsequently scanned with positron emission tomography (PET). A potential side effect of radiation is the induction of cancer. However, no harm in a human individual or in a large population exposed at doses as low as those delivered in this procedure has been reported. The estimation of risk of harm can be obtained only by extrapolation from much higher doses. Methylphenidate is a mild central nervous system stimulant used to treat attention deficit disorder and narcolepsy. It increases heart rate and blood pressure and can cause a behavioral "high". It can also elicit negative feelings of anxiety. In the event that either cardiovascular or behavioral complications occur, they can be effectively treated with an intramuscular injection of a neuroleptic. Since methylphenidate will be administered intravenously, the likelihood of cardiac stimulation is higher. There is also some evidence that methylphenidate may lower the seizure threshold in some individuals who have a prior history of seizure disorders, and very rarely, in individuals with no history of seizure disorders. Therefore, methylphenidate should not be given to patients with cardiac disease or patients with a past history of seizure disorders. Arterial catheterization has the following rare but possible complications: pain during placement of the catheter, a risk of bleeding at the skin puncture site, the possibility of local infection and temporary or permanent impairment of the blood supply to portions of the hand. Whenever blood is removed or a substance is injected by venipuncture, there is minor discomfort and a slight possibility of local bleeding in the tissues.