F-DOPA is a simple yet powerful, noninvasive diagnostic tool that allows for the early diagnosis and proper medical management of patients with symptoms of Parkinson’s disease. Parkinsonian syndromes, such as decreased body movements, stiffness or rigidity, tremors or shaking of hands, are either caused by Parkinson’s disease or by some other medical conditions. F-DOPA is the diagnostic tool to differentiate if a patient has parkinsonian syndromes or Parkinson’s disease , confirm the diagnosis of Parkinson’s disease and to follow the rate of disease progression.
General Tracer Class: Investigational Diagnostic PET Radiopharmaceutical in the US.
Target: 1. Neurology/Psychiatry: Dopamine receptors in the brain.
2. Oncology: a) Amino acid (AA) transporters (a feature of many benign and malignant tumors); b) overexpression of DOPA decarboxylase is a characteristic feature of neuroendocrine tumors (NET); this enzyme is usually co-expressed with other neuroendocrine markers such as chromogranin-A.
Molecular Process Imaged: 1. Regional distribution of neurotransmitter dopamine in the brain.
2. Amino acid uptake and metabolism in tumors.
Mechanism for in vivo retention:
1. Neurology/Psychiatry: 18F-FDOPA crosses the blood-brain barrier where it is converted to 18F-Fluorodopamine by enzyme amino acid decarboxylase (AADC) in the striatum. 18F-Fluorodopamine is stored in presynaptic vesicles until the neuron activation triggers its release and subsequent binding to the dopamine receptors.
2. Oncology: [18F]-FDOPA is taken up into cancer cells by (predominantly L-type) AA transporters, which are overexpressed in cancer (6). In the cancer cell, AA may enter various pathways (e.g., peptide, protein, purine, pyrimidine or hormone synthesis; act as methyl group donors etc). FDOPA in particular undergoes decarboxylation; increased activity of L-DOPA decarboxylase is a hallmark of (benign and malignant) neuroendocrine tumors (4). In NET, F-DOPA uptake reaches a plateau within 20 min after intravenous injection.
Recommended Activity and Allowable Mass
DOSAGE AND ADMINISTRATION: IV administration, typically 6-12 mCi (222-444 MBq) with a specific activity of 20 to 40 MBq (740 to 1480 mCi) per micromole .
Dosimetry: The effective dose equivalent (whole body) is estimated to be 0.026 mSv/MBq (100 mrem/mCi) for adults. The critical organs are the kidneys, the bladder, and the pancreas; they receive 0.089 mGy/MBq (389 mrad/mCi), 0.215 mGy/MBq (797 mrad/mCi and 0.030 mGy/MBq (110 mrad/mCi) respectively .