Fluorodopa F18 (Page 3 of 3)

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

In dopaminergic nerve terminals in the brain, Fluorodopa (FDOPA) F 18 is decarboxylated by amino acid decarboxylase to Fluorodopamine (FDA) F 18 and stored in presynaptic vesicles in the brain. The accumulation of F 18 FDA in the striatum is visually detected in the PET scan.

12.2 Pharmacodynamics

Optimal PET imaging is achieved between 75 to 90 minutes after administration of Fluorodopa F 18 Injection based on its pharmacokinetics. The relationship between Fluorodopa F 18 dose and plasma concentration is not fully characterized.

12.3 Pharmacokinetics

Distribution
Following the intravenous administration, Fluorodopa F 18 is cleared from the blood with a biologic half-life of about 1 to 3 hours. The time course of “background” brain radioactivity after Fluorodopa F 18 was evaluated. F 18 activity in the cerebellum was greater than the parietal or occipital cortex during the first 30 minutes after Fluorodopa F 18 suggesting regional differences in amino acid transport.

EliminationFluorodopa F 18 is cleared from the blood and tissue within 24 hours.

Metabolism: Fluorodopa F 18 is decarboxylated by aromatic amino acid decarboxylase in the striatum to Fluorodopamine F 18. Fluorodopamine F 18 is also metabolized via monoamine oxidase to yield [18 F] 6-fluoro-3,4-dihydroxyphenylacetic acid (18 FDOPAC) and subsequently by COMT to yield [18 F]6-fluorohomovanillic acid (18 FHVA).

Elimination: 80% of the radioactivity is eliminated through the urine. Urine radioactivity peaks at about 30 minutes post-injection. The radiation absorbed dose to the bladder wall is reduced by emptying the bladder just before scanning.

14 CLINICAL STUDIES

The safety and efficacy of F-18 FDOPA were evaluated in a prospective single-arm study conducted at a single center that enrolled 68 adult patients with possible Parkinsonian syndrome (PS). In the study, F-18 FDOPA image reads were compared to a reference clinical diagnostic standard of Parkinsonian syndrome or non-Parkinsonian syndrome (non-PS) established at 6 to 9 months after the F-18 FDOPA PET scan by a movement disorder specialist blinded to F-18 FDOPA PET results. The reference clinical diagnostic standard for PS included Parkinson’s disease (PD), progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), and multiple system atrophy (MSA). These conditions have been associated with dopaminergic neurodegeneration and F-18 FDOPA PET imaging was not designed to distinguish among the conditions. The reference clinical diagnostic standard for non-PS included essential tremor (ET) diagnosis, vascular parkinsonism, drug-induced parkinsonism, and other non-PS diagnoses.

Carbidopa (150 mg) was administered orally to patients approximately 60 minutes prior to the administration of Fluorodopa F 18 Injection. Each patient was injected 5 mCi F-18 FDOPA (range 4.5-5.5 mCi), and PET images were acquired 80-100 minutes post injection.

F-18 FDOPA PET images were evaluated independently by 3 readers blinded to clinical information who had no other role in patient assessment. Patients with at least one cardinal feature of PS were referred to the study by physicians who were uncertain of a diagnosis. Thirty-three of these patients had symptoms for 2 years or less. Fifty-six of these patients completed F-18 FDOPA PET imaging and at least 6 month clinical follow-up. Among these 56 patients, 32% were female and 68% were male. Mean patient age was 66 years. Thirty-three patients were categorized as PS, and twenty-three patients were categorized as non-PS based on minimum 6 month clinical follow-up by a movement disorder specialist.

Table 5 shows the positive percent agreement and negative percent agreement of F-18 FDOPA Injection PET image results with the reference clinical diagnostic standard. Positive percent agreement represents the percent of patients with positive F-18 FDOPA PET images among all the patients with a clinical diagnostic reference standard of PS. Negative percent agreement represents the percent of patients with negative F-18 FDOPA PET images among the patients with a non-PS clinical diagnostic reference standard.

Table 5. Positive and Negative Percent Agreement for F-18 FDOPA Injection PET Imaging
n=56 Patients

Positive percent agreement

Positive test/Clinical PS

(95 % CI)

Negative percent agreement

Negative test/Clinical non-PS

(95 % CI)

Reader 1

24/33

73% (55, 87)

21/23

91% (72, 99)

Reader 2

16/33

49% (31, 67)

21/23

91% (72, 99)

Reader 3

19/33

58% (39, 75)

19/23

83% (61, 94)

The effectiveness of F-18 FDOPA PET as a screening or confirmatory test and for monitoring disease progression or response to therapy has not been established.

16 HOW SUPPLIED/STORAGE AND DRUG HANDLING

Fluorodopa F 18 Injection (NDC 13267-346-57) is supplied as a clear, colorless injection in a septum capped glass vial containing between 37 MBq/mL to 1,480 MBq/mL (1 mCi/mL to 40 mCi/mL), of Fluorodopa F 18 at calibration time, in 28 mL ±1 mL.

Storage
Store the Fluorodopa F 18 Injection vial upright in a lead shielded container at 25°C (77°F); excursions permitted between 15ºC to 30°C (59ºF to 86°F). Avoid direct light.

The expiration date and time are provided on the container label. Use Fluorodopa F 18 Injection within 8 hours from the time of the end of synthesis (EOS).

Handling
This radiopharmaceutical is for distribution and use by persons licensed authorized by the U.S. Nuclear Regulatory Commission or the relevant regulatory authority of an Agreement State. Store and dispose of Fluorodopa F 18 in compliance with the appropriate regulations of the government agency authorized to license the use of this radionuclide.

17 PATIENT COUNSELING INFORMATION

Patient Preparation
Instruct patients to:
• Drink water in the 4 hours before their PET study and continue hydration with water or other fluids (as tolerated) after the study.
• Void 70 minutes after the administration of Fluorodopa F 18, before the start of the imaging study, and as frequently as possible after the study is complete for a total of 12 hours [see Dosage and Administration (2.3)].

Lactation
To decrease radiation exposure to a nursing infant, advise a lactating woman to pump and discard breastmilk for at least 24 hours (12 half-lives) after administration of Fluorodopa F 18 Injection. (8.2)

Manufactured & Distributed by:
The Feinstein Institutes for Medical Research
Cyclotron/Radiochemistry Facility
350 Community DriveManhasset, New York 11030

FDOPA Vial Label
(click image for full-size original)

FDOPA Lead Pig Label
(click image for full-size original)
FLUORODOPA F18 fluorodopa f18 injection
Product Information
Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:13267-346
Route of Administration INTRAVENOUS DEA Schedule
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
FLUORODOPA F-18 (FLUORODOPA F-18) FLUORODOPA F-18 40 mCi in 1 mL
Inactive Ingredients
Ingredient Name Strength
EDETATE DISODIUM 1.46 mg in 1 mL
ASCORBIC ACID 5 mg in 1 mL
ALCOHOL 23.68 mg in 1 mL
Packaging
# Item Code Package Description Multilevel Packaging
1 NDC:13267-346-57 30 mL in 1 VIAL, GLASS None
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
NDA NDA200655 10/10/2019
Labeler — THE FEINSTEIN INSTITUTES FOR MEDICAL RESEARCH (110565913)
Registrant — THE FEINSTEIN INSTITUTES FOR MEDICAL RESEARCH (110565913)
Establishment
Name Address ID/FEI Operations
THE FEINSTEIN INSTITUTES FOR MEDICAL RESEARCH 110565913 positron emission tomography drug production (13267-346)

Revised: 01/2021 THE FEINSTEIN INSTITUTES FOR MEDICAL RESEARCH

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