What to ExSPECT In the Era of Isotope Shortages

SPECT myocardial perfusion imaging with technetium-99m (Tc99m) shows normal findings. Source: Daniel S. Berman, MD, director of cardiac imaging and nuclear cardiology at Cedars-Sinai Heart Institute
While nuclear cardiologists await a normal supply of molybdenum-99 (Mo-99), the parent isotope of technetium-99m (Tc-99m), they have found ways to cope, including using other radiopharmaceuticals—which can challenge standard protocols—or by relying more on PET and CT imaging.

Survey says...

A survey conducted in August 2009 of nuclear pharmacists relating to the shortage of Mo-99 revealed some startling revelations. Out of 97 respondents:
  • 82 percent were using thallium-201(Tl-201) to replace Tc-99m agents;
  • 81 percent had decreased their dosage;
  • 76 percent had rescheduled patient orders to another day or time;
  • 71 percent cancelled backup doses;
  • 68 percent eliminated standing orders; and
  • 21 percent sent doses with later calibration times.

Practices and facilities across the U.S. have had to be creative to operate efficiently and safely while Tc-99m stockpiles remain precarious at best. At the Cleveland Clinic, Manuel D. Cerqueira, MD, chairman of the department of nuclear medicine, has lowered Tc-99m doses and splits SPECT myocardial perfusion imaging (MPI) rest/stress studies between Tl-201 and Tc-99m, respectively.

At Cedars-Sinai Heart Institute, Los Angeles, Daniel S. Berman, MD, director of cardiac imaging and nuclear cardiology, estimates that approximately 20 to 30 percent of patient studies have been affected by the shortage—either by switching to Tl-201 or rubidium-82 (Rb-82) PET. “It is something that varies week to week and even day to day as the generator gets old,” Berman says.

From the perspective of the patients, the studies are not timely, nor are they certain, Cerqueira adds.
 

Knowing the protocols

The advantage of Tl-201 comes in its ability to make perfusion defects more obvious compared to Tc-99m, according to Berman. However, it doesn’t bind as well within the cell and therefore has a limited window for imaging. Thallium affords less flexibility in terms of patient scheduling because the patient has to be imaged within 15 minutes of injection for stress (see sidebar). “With Tc-99m, it’s acceptable to wait even longer than an hour before starting the imaging,” says Berman. A Tl-201 study also exposes the patient to more than two times the radiation dose as Tc-99m, he adds.

The sudden reliance on Tl-201 has caused a flood of inquiries into the offices of the Intersocietal Commission for the Accreditation of Nuclear Medicine Laboratories (ICANL), according to Mary Beth Farrell, MS, technical manager of ICANL. “Technologists are unsure of how to image with thallium,” Farrell says. “From our perspective, accredited facilities are required to have a written Tl-201 protocol and be aware of the complexities of imaging with Tl-201. However, they are not required to submit the protocol to us.”

Berman and colleagues have written about a novel approach using a dual-isotope protocol (Tl-201 stress-Tc-99m rest) using a high-speed camera (J Am Coll Cardiol Img 2009;2:273-282). Berman reported that exams were completed in 20 minutes, “with image quality and radiation dosimetry similar to
those observed with a conventional rest/stress Tc-99m protocol.”
 

Rubidium PET

Thallium & Technetium Require Different Protocols
Thallium-201 (Tl-201) and technetium-99m (Tc99m) have different physical properties and thus require different protocols.

With Tl-201, patients must be imaged within 10 minutes of injection at peak exercise stress. Technologists must then wait four hours for the thallium to redistribute to scan the patient at rest. To obtain both sets of Tl-201 images in the same day, the stress images must be acquired in the morning and the rest images at least four hours later.

The Tc99m tracers do not redistribute, so there is more flexibility in the timing of the imaging. Either the stress or rest images can be acquired first. Because the Tc99m tracers do not redistribute, two injections of the radiopharmaceutical are required—one at stress and one at rest. The two injections or doses differ only in the amount, usually given in a ratio of 3.5-4:1.
Both Cerqueira and Berman have been dealing with the isotope crisis by switching some of their SPECT studies to Rb-82 PET. But Rb-82 PET has its own challenges, primarily availability and reimbursement.

Rb-82 is produced via a generator, which costs approximately $32,000 for 28 days, limiting the number of sites that will offer Rb-82 PET routinely, says Cerqueira. “In 2007, close to eight million cardiac SPECT studies were performed, compared with fewer than 100,000 cardiac PET studies. The number of SPECT cameras in the U.S. is much greater than that of PET scanners. So, it is difficult for everybody to convert to PET,” he says. In addition, not all insurance carriers cover Rb-82 PET. “We have to do a lot more administrative work to get approval,” Cerqueira adds.
 

Other strategies

Echocardiography has proven its efficacy with decades of validation studies. There are some instances where insurance companies won’t cover Tl-201. Depending on the individual patients, echo can easily be used in some of these circumstances, says Berman. He also recommends coronary CT angiography (CCTA) in select cases.

Another option is to do a stress only study in patients who have a low pretest probability of the disease. “If the stress is normal, there is no need to do the rest studies,” Cerqueira says.

Berman recommends that practices plan ahead and ask the suppliers when to expect the shortage and order TI-201 in advance for those days. If Rb-82 is available, he suggests relying on Rb-82 PET for the lean times.

In the meantime, the Chalk River reactor in Ontario, Canada, is expected to be back online this month, once again producing Mo-99. Nevertheless, astute nuclear cardiologists and technologists need to remember the various strategies they can employ to overcome any future shortage of Tc-99m agents. In the long run, the better the coping mechanisms, the better the patients are served, bringing the least amount of disruption to the nuclear cardiology service.

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