Project Identifier: BNL-93-249
Project Title:
Imaging the Dopamine Presynaptic Neuron with 11-C-Methylphenidate
Principle Investigator:
Dr. Joanna S. Fowler
Project started in: 1993
Project Funding Information:
Project received funding in Fiscal Year 1995.
Project used human subjects in Fiscal Year 1995.
Funding Sources:
Project does not involve use of multiple protocols/subprojects.
IRB Review:
Type of Review: Full Board
Most Recent Approval: August 02, 1995
Number of Human Subjects in the Last Reporting Period for this Project: 9
(Reporting periods vary.)
Type of Human Subjects Involvement:
Internal administration of radioactive substances to human subjects.
Methylphenidate (Ritalin) is a mild central nervous system stimulant used primarily in the treatment of attention-deficit hyperactivity disorder (ADHD) and narcolepsy. These studies are designed to measure the pharmacokinetics and regional localization of methylphenidate in the brain and in the body using C-11-labeled methylphenidate and positron emission tomography (PET). They are also designed to assess the association between methylphenidate kinetics in the brain and the behavioral effects of a pharmacologically active dose of methylphenidate (0.5 milligram intravenously). Another part of this study will compare methylphenidate binding in different types of patients to assess its sensitivity to degeneration of dopaminergic neurons and to altered presynaptic function. These studies are expected to provide insight into the behavior of methylphenidate and also to examine the feasibility of using C-11-methylphenidate as a sensitive indicator for the loss of dopaminergic nerve terminals. Approximately 15 normal volunteers (ages 18-55), 15 normal subjects (ages 55-90), 15 cocaine abusers, 15 Parkinson's disease patients and 15 patients with Alzheimer's disease will be studied. Subjects will be males and females. We will exclude all patients that are medically unstable, patients for whom discontinuation of drugs poses a risk and patients with peripheral vascular disease. Subjects will receive a maximum of 24 millicuries (mCi) of C-11-methylphenidate per quarter in 1-3 injections. 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 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.