Staff at the first imaging center in the United States to receive and utilize doses of the new radiopharmaceutical, Cerianna™ (fluoroestradiol F 18) injection, describe how it could impact their practice and the subsequent treatment of patients with recurrent or metastatic breast cancer.
Photography by Winni Wintermeyer
In May 2020, Cerianna™ (Zionexa USA, Indianapolis, IN), was approved by the United States Food and Drug Administration (FDA) as the first F-18 PET imaging agent to be indicated as an adjunct to biopsy for the detection of estrogen receptor (ER)-positive lesions in patients with recurrent or metastatic breast cancer (MBC).1,2 Approximately 75 percent of breast cancers in women and 99 percent in men are ER-positive,3,4 and almost all these patients will be candidates for endocrine therapies.
Patients with ER-positive MBC may respond well to appropriate therapy, but these therapies will not be effective if there is no ER expression in the metastatic lesions, so it is important to determine ER status to guide therapy.5,6 In studies, 18F-Fluoroestradiol was shown to be as effective in determining ER status in MBC as immunohistochemistry (IHC) tissue biopsy,7 and is especially valuable in evaluating cases with multiple metastases.
“It didn’t take long for PETNET to manufacture the product and to provide us with a dose for the first patient. It’s as simple as delivering any other radiopharmaceutical, so not difficult at all.”
Cerianna reaches first US imaging center
PETNET Solutions Inc., a Siemens Healthineers company (Knoxville, TN, USA), manufactured and distributed the first commercial dose of Cerianna within the United States in December 2020 at its San Francisco production site.8 The first location to receive and utilize Cerianna was the Northern California PET Imaging Center (NCPIC) based in Sacramento. Established in 1992 as a non-profit, public-benefit corporation, NCPIC was one of the first free-standing outpatient PET centers and the first non-research-based PET center in the United States.
The NCPIC team has helped establish data to support many US clinical indications for PET in oncology, which constitutes around 95 percent of their work, says Ruth Tesar, NCPIC’s CEO. “We have had a very long relationship with PETNET and the company looks to us to pave the way in helping get a new tracer or modality out to the community,” Tesar says. “It didn’t take long for PETNET to manufacture the product and to provide us with a dose for the first patient. It’s as simple as delivering any other radiopharmaceutical, so not difficult at all.”
More specific imaging in breast cancer
“PET has been really successful because it can image many types of cancer, but what the PET community has wanted for many years is for the radiopharmaceuticals and the procedures that we offer to be much more specific,” Tesar says. Fludeoxyglucose F 18 injection (18F FDG), the most widely used PET and PET/CT radiopharmaceutical in oncology is, ”a great agent, very easily accessible, and very inexpensive to use, but one of its limitations is that it is very non-specific,” says Jaideep S. Sohi, MD, NCPIC’s medical director. “On an FDG PET scan you can see regions that are positive that could be either malignant, benign infectious, or inflammatory disorders. Oftentimes it causes a diagnostic dilemma,” he notes. “With Cerianna we get really specific imaging, and that’s a huge benefit for patients with ER-positive breast carcinoma. It has the potential to help oncologists choose the most appropriate therapy for their patients, so we’re very excited in that respect,” he says.
“With Cerianna we get really specific imaging, and that’s a huge benefit for patients with ER-positive breast carcinoma.”
Practical considerations with Cerianna
PET/CT scans with Cerianna are acquired in a very similar way to those with FDG, says Hitesh Patel, CNMT, one of the three nuclear medicine technologists at NCPIC. Yet one noticable difference Hitesh notes is in the patient preparation, in which patients must fast for 4-6 hours before an injection of FDG, whereas this is not necessary with Cerianna. “The recommended dose for Cerianna is 6 (range 3-6) millicuries, whereas FDG is weight dependent, so we average about 12 millicuries per patient,” Patel says. Sohi stresses the importance of having patients stop certain breast cancer medications, such as ER modulators or down-regulators like tamoxifen or fulvestrant, that can decrease uptake of Cerianna and reduce detection of ER-positive lesions. “It’s crucial to ensure that patients are off these medications for typically 8 weeks (tamoxifen) or 28 weeks (fulvestrant) before the scan. This is a key point compared with other PET tracers,” he says.
When interpreting a Cerianna scan, “it is important to take the time to look at prior imaging studies and compare them in detail, because often the findings on Cerianna PET may be subtle and could be missed,” Sohi advises. “The great thing about Cerianna is that you only see truly abnormal uptake in tissues that are ER-positive, such as breast carcinoma or pelvic or uterine malignancies, and not in other normal tissues,” he says. “Since this tracer is metabolized through the liver and excreted through the biliary tract, these areas will also show high activity,” Sohi adds.
Educating patients, payers, and clinicians
As part of their role in advocating for patient care, the NCPIC team works hard to raise awareness around new imaging opportunities such as Cerianna. “We’re focused on patient-centered medicine,” Sohi stresses.
One challenge for patients—in addition to their willingness to come in and undergo this imaging—is reimbursement, which is still being negotiated as of January 2021, he notes. Tesar is optimistic that this process will not take long. “It is a lot easier than it was 20 years ago when we started, but it takes a team to educate the right people to get coverage for this procedure, because they don’t get to see how it changes patients’ lives. We’re a little more passionate about getting coverage quickly because we get to see how it benefits people,” she admits.
Oncologists also need education about what is available to them, Sohi adds. “They’re extremely excited about what Cerianna has to offer because they see patients every day who could benefit from it,” he says. When the team used Cerianna for the first time, “because this was a new modality and we were the first to use it in the region, I made sure to call the referring physician to discuss what I observed on the scan and how the findings could potentially affect their treatment plan,” Sohi recalls. He was able to confirm that, “based on what we saw, the referring physician felt Cerianna PET helped him in the treatment- decision process and was going to modify the therapy for the patient accordingly.”
Future of Cerianna and precision oncology
Sohi believes Cerianna can make a difference to the overall treatment planning and care of MBC patients. He anticipates that later in 2021, after it becomes widely available and reimbursement has been finalized, Cerianna will become part of established breast-cancer management guidelines. “Then we will see many more patients being able to utilize this imaging modality,” he says. Long term, he foresees combinations of imaging modalities, laboratory tests, and genomic testing being used in precision oncology. “We’re slowly but surely increasing our panel of imaging agents to look at specific tumors, and I see that expanding rapidly in the next few years,” he predicts.
About the author
Linda Brookes, MSc, is a freelance medical writer and editor, dividing her time between London and New York, working for a variety of clients in the healthcare and pharmaceutical fields.
Indications and Usage
- 18F-FES is a radioactive diagnostic agent indicated for PET imaging.
- 18F-FES is indicated for the detection of ER-positive lesions as an adjunct to biopsy in patients with recurrent or metastatic breast cancer.
Limitations of Use
- Tissue biopsy should be used to confirm recurrence of breast cancer and to verify ER status by pathology. 18F-FES is not useful for imaging other receptors, such as HER2 and PR.
Important Safety Information
Adverse Reactions – Reported adverse reactions include: injection site pain and dysgeusia.
Radiation Risks – Ensure safe drug handling and patient preparation procedures to protect patients and health care providers from unintentional radiation exposure.
Risk of Misdiagnosis – Do not use CERIANNA in lieu of biopsy when biopsy is indicated in patients with recurrent or metastatic breast cancer.
Contraindications – None.
Use in Specific Populations – Lactation: interrupt breastfeeding.
Advise a lactating woman to avoid breastfeeding for 4 hours after CERIANNA administration.
To report SUSPECTED ADVERSE REACTIONS, contact Zionexa US Corp at +1.844.946.6392 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
Dosage and Administration
Dosage form and strengths
- Injection: clear, colorless solution in a multiple-dose vial containing 148 MBq/mL to 3,700 MBq/mL (4 mCi/mL to 100 mCi/mL) of Cerianna at end of synthesis.
- Drink water to ensure adequate hydration prior to administration of 18F-FES
- Continue drinking and voiding frequently during the first hours following administration to reduce radiation exposure
Dosage and administration
- Activity recommended is 222 MBq (6 mCi), with a range of 111 MBq to 222 MBq (3 mCi to 6 mCi)
- Administration : single IV injection of 10 mL or less over 1 to 2 minutes
- Use aseptic technique and radiation shielding when withdrawing and administering FES.
- Visually inspect the radiopharmaceutical solution
- FES may be diluted with 0.9% Sodium Chloride Injection, USP
- Assay the dose in a suitable dose calibrator prior to administration
Follow FES injection with an IV flush of 0.9% Sodium Chloride injection, USP
Dosage form and strengths
Fludeoxyglucose F 18 5-10mCi as an IV injection
Indications and Usage
Fludeoxyglucose F 18 Injection is indicated for positron emission tomography (PET) imaging in the following settings:
- Oncology: For assessment of abnormal glucose metabolism to assist in the evaluation of malignancy in patients with known or suspected abnormalities found by other testing modalities, or in patients with an existing diagnosis of cancer.
- Cardiology: For the identification of left ventricular myocardium with residual glucose metabolism and reversible loss of systolic function in patients with coronary artery disease and left ventricular dysfunction, when used together with myocardial perfusion imaging.
- Neurology: For the identification of regions of abnormal glucose metabolism associated with foci of epileptic seizures.
Important Safety Information
- Radiation Risks: Radiation-emitting products, including Fludeoxyglucose F 18 Injection, may increase the risk for cancer, especially in pediatric patients. Use the smallest dose necessary for imaging and ensure safe handling to protect the patient and health care worker.
- Blood Glucose Abnormalities: In the oncology and neurology setting, suboptimal imaging may occur in patients with inadequately regulated blood glucose levels. In these patients, consider medical therapy and laboratory testing to assure at least two days of normoglycemia prior to Fludeoxyglucose F 18 Injection administration.
- Adverse Reactions: Hypersensitivity reactions with pruritus, edema and rash have been reported; have emergency resuscitation equipment and personnel immediately available. Full prescribing information for Fludeoxyglucose F 18 Injection can be found at the conclusion of this publication.