The U.S. Food and Drug Administration (FDA) has bolstered its requirement for safety labels on rubidium-82 (Rb-82) generators for PET studies. The action follows reports of a "serious incident" of excess radiation exposure to patients caused by what the FDA called "user error."
The generators produce the radioactive isotope Rb-82 for use in PET myocardial perfusion imaging. Contrast developer Bracco Diagnostics markets the CardioGen-82 rubidium generator, while radiopharmaceutical firm Jubilant DraxImage offers the Ruby-Fill Rb-82 generator.
The FDA's April 29 communiqué on the safety label changes follows March 25 statements from both Jubilant and Bracco about the incident. Their identical messages cited "high-level radiation exposure" due to user error and a "failure to follow the eluate testing protocol."
According to the FDA and the companies, incorrect solutions, which included calcium, were used to elute -- or extract -- Rb-82 from the generator. These solutions interacted with strontium-82 (Sr-82) and strontium-85 (Sr-85), which are used exclusively to manufacture Rb-82.
"These radioisotopes of strontium then 'break through' into the rubidium injection administered to patients," the FDA explained. "The strontium isotopes can deposit high levels of radioactivity in organs including the bone, which can lead to suppressed bone marrow function and suppression of the immune system. Additional long-term risks could include radiation-induced cancers."
The revised FDA safety labels include instructions on the proper use of rubidium generators and warnings about the serious consequences of improper procedures. The agency also mandates training for all imaging facilities that use the CardioGen-82 and Ruby-Fill systems.
To avoid any incidents in the future, the FDA, Bracco, and Jubilant also outlined the following safety procedures for Rb-82 generators:
- Use only additive-free 0.9% sodium chloride injection (normal saline) to elute an Rb-82 generator. Strictly adhere to the mandatory eluate testing protocol.
- Immediately stop patient infusion and permanently discontinue the use of the affected Rb-82 generator if any solution other than additive-free 0.9% sodium chloride injection is used for elution.
- If a patient is administered Rb-82 injection prepared with the incorrect eluent, evaluate the patient's radiation absorbed dose, and monitor for the effects of radiation to critical organs such as the bone marrow.
In addition, both Bracco and Jubilant plan to conduct testing to evaluate the risk posed by the Sr-82 and Sr-85 breakthrough process. Jubilant also stated that it is "considering a range of possible additional risk mitigation options and will provide follow-up communications as appropriate."
The FDA also asked healthcare professionals and consumers to report any adverse events or quality problems associated with the devices to its MedWatch adverse event reporting program. In the meantime, the agency is urging patients to continue to undergo Rb-82 PET myocardial perfusion scans and consult their physicians about any concerns.
