fluoroestradiol F 18 (Rx)

<1%

General disorders: Injection-site pain

Neurological and gastrointestinal disorders: Dysgeusia

Contraindications

None

Cautions

Radiation risks

• Diagnostic radiopharmaceuticals expose patients to radiation
• Radiation exposure is associated with a dose-dependent increased risk of cancer
• Ensure safe drug handling and patient preparation procedures to protect patients and healthcare providers from unintentional radiation exposure

Misdiagnosis risks

• Inadequate tumor characterization and other ER+ pathology

  • Breast cancer may be heterogeneous within patients and across time
  • Fluoroestradiol F 18 images ER and is not useful for imaging other receptors (eg, HER2, PR)
  • Uptake is not specific for breast cancer and may occur in a variety of ER+ tumors that arise outside of the breast, including uterus and ovaries
  • Do not use in lieu of biopsy when biopsy is indicated in patients with recurrent or metastatic breast cancer

• False-negative scan

  • A negative scan does not rule out ER+ breast cancer
  • Pathology or clinical characteristics that suggest a patient may benefit from systemic hormone therapy should take precedence over a discordant negative scan

Drug interaction overview

• Certain classes of systemic endocrine therapies, including ER modulators and ER down-regulators, block ER, reduce the uptake of fluoroestradiol F 18, and may reduce detection of ER+ lesions after administration
• Drugs from these classes (eg, tamoxifen, fulvestrant) may block ER for up to 8-28 weeks, respectively
• Do not delay indicated therapy in order to administer fluoroestradiol F 18
• Administer fluoroestradiol F 18 before starting systemic endocrine therapies that block ER

Pregnancy

All radiopharmaceuticals have potential to cause fetal harm depending on fetal stage of development and the magnitude of radiation dose

Advise pregnant females of the potential risks of fetal exposure to radiation from administration

There are no available data on use during pregnancy

No animal reproduction studies have been conducted

Lactation

There are no data on the presence of fluoroestradiol F 18 in human milk, or its effects on breastfed infants or milk production

Lactation studies have not been conducted in animals

Advise breastfeeding females to avoid breastfeeding for 4 hr after administration

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Fluoroestradiol F 18 binds estrogen receptor (ER)

The following binding affinity: Kd = 0.13 ± 0.02 nM, Bmax = 1901 ± 89 fmol/mg, and IC50 = 0.085 nM, was determined in an ER+ human breast cancer cell line (MCF7)

Distribution

Protein bound: 95%

Distributes primarily to hepatobiliary system, and also to small and large intestines, heart wall, blood, kidney, uterus, and bladder

Metabolism

Metabolized in liver; 20 minutes after injection, ~20% of circulating radioactivity in plasma is in the form of nonmetabolized fluoroestradiol F 18; at 2 hr after injection, circulating fluoroestradiol F 18 levels are <5% of peak concentration

Elimination

Excretion: Biliary and urinary

IV Preparation

Use aseptic technique and radiation shielding when withdrawing and administering

Visually inspect solution; do not use if it contains particulate matter or is cloudy or discolored (fluoroestradiol F 18 is a clear, colorless solution)

May be diluted with 0.9% NaCl

Assay dose in a suitable dose calibrator before administration

Patient preparation

• Instruct patients to drink water to ensure adequate hydration before administration and continue drinking and voiding frequently during the first hours following administration to reduce radiation exposure

Image acquisition

• Position patient supine with arms above the head, if possible
• Recommended start time for image acquisition is 80 minutes after IV administration
• Scan duration adapted from range of 20-30 minutes and imaging start times adapted within range of 20-80 minutes may be customized according to equipment used and patient and tumor characteristics for optimal image quality

Image interpretation

• Uptake of fluoroestradiol F 18 depends on ER density and function in tumors and physiologic tissue, including liver, ovary, and uterus
• Base detection of ER+ tumors on comparison with tissue background outside of organs with high physiologic uptake and regions with high activity due to hepatobiliary and urinary excretion
• See radiation dosimetry in prescribing information for specific tissues

Radiation safety

• Fluoroestradiol F 18 is a radioactive drug; only authorized persons qualified by training and experience should receive, use, or administer
• Handle with appropriate safety measures to minimize radiation exposure during administration
• Use waterproof gloves and effective radiation shielding, including syringe shields, when preparing and handling

IV Administration

Administer IV over 1-2 minutes

Follow injection with IV flush of 0.9% NaCl

Dispose of any unused drug in compliance with radiopharmaceutical regulations

Storage

Store at 20-25ºC (68-77ºF)

Store upright in original container with radiation shielding

Expiration date and time are provided on the container label

Use within 10 hr from the time of the end of synthesis